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Bengaluru: An international collaboration of over 100 scientists and geneticists have traced the genetic origin of modern domestic horse, the Equus caballus, to Russia.

The research narrows the location of horse domestication the steppes of Western Europe, where the Volga and Don rivers intersect, to 4,200 years ago from where and when horses spread to the rest of the world.

The study was led by molecular archaeologist Ludovic Orlando at University of Paul Sabatier in Toulouse, France. Genetic analysis was performed on 273 reconstructed ancient horse genomes from fossils of ancient horses found in various parts of Europe and Asia.

The team further identified two genes in horses, the GSDMC and ZFPM1 genes, which provided modern horses locomotive and behavioral adaptations that helped with horse-back riding and domestication.

The research is thought to be the most comprehensive analysis of available genetic data and the findings were authored by 162 researchers. The paper was published in the journal Naturethis week.

The Bronze Age spread through Europe and Asia between 5,000 and 4,000 years ago, which is when writing systems, pottery, codified law, city-states, warfare, and agriculture came into existence in human society.

Analysis of human genomes from this era has previously revealed a massive expansion and spreading out of population from the Western Eurasian steppes into the regions of Central and Eastern Europe in around the 3rd millennium BCE. Historical records also indicate a rapid expansion in the population of horses across Eurasia at this time.

This is also the time period where horse ancestors that roamed grasslands in North America came over to Asia by crossing over the fully frozen Bering land bridge.

Based on their findings, the authors write that the people who lived in the region where the Volga and Don rivers intersect, bred horses, which moved along with humans.

However, researchers also identify other species of horse that were domesticated in pockets, whose populations were eventually replaced by horses that came from this region, called the DOM2 horses as they spread out in the second millennium, around 2200 BCE.

The journey of horses and humans is traced together with equestrian culture, which shows expansion of objects like spoke-wheeled chariots.

Also read: 85% world population inhabit areas directly affected by human-induced climate change, study says

Horse ancestors are thought to have roamed the grasslands in North America, and came over to Asia by crossing over the fully frozen Bering land bridge before the Bronze Age.

To the early days of the Bronze Age, four lineages of horses were identified. One lineage was traced to a different species called Equus lenensis, which existed in northeastern Siberia. A second lineage was spread out over the western parts of Europe. A third lived in the Urals, while the fourth, the DOM2, lived in the Western Eurasian steppes.

Genetic analyses traced the DOM2 to have originated in the region where the Volga and the Don rivers intersected, and where the existing human population domesticated these horses for specific genes by breeding. The DOM2 horses eventually replaced the populations of other native horses thanks to favourable genetics that allowed them to live with humans.

The authors used data about the analysis of human expansion and compared the expansion of the modern horse genome with it.

From bones of horses buried with spoke-wheeled chariots during around 2000 BCE, authors surmised them to be of the DOM2 horses. Such horses were also found in Central Anatolia; visual representations from about 1900 BCE are available. They also identified other geographic regions where the horses pre-dated chariots, indicating that horseback riding spread before chariots.

The two genes identified indicated key behaviours that humans bred horses for the GSDMC gene is responsible for a strong spine, back, and gait, while the ZFPM1 gene is involved in mood regulation and aggression. The combination of the genes indicated that horses were bred to be more mobile, including being able to run long distances and bear weight, and also to be more docile to be able to live and work alongside humans.

The findings finally provide an answer to extensive debates about the origins and the spread of modern domestic horses.

Along with horses, the research also explains the evolution of two family of languages as different groups of peoples spread across Eurasia.

All European languages have evolved from the hypothetical Proto-Indo-European (PIE) language, which then has sub-families of languages. In the Indo-Iranian group of languages, which consists of languages spoken in the Persian region and in northern India, there is an extensive vocabulary for horse- and equestrian culture-related words, while the earlier parent PIE language has a sparse vocabulary for equine words.

We thus conclude that the new package of chariotry and improved breed of horses, including chestnut coat colouration documented both linguistically and genetically, transformed Eurasian Bronze Age societies globally within a few centuries after about 2000 BC, write the authors.

(Edited by Paramita Ghosh)

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Adapted from a story that originally appeared here in the University of Utah Health newsroom.

When Faith Bowman was deciding where to attend graduate school, the University of Utah wasnt exactly at the top of her list. Coming from Wisconsin, she didnt know much about the school or the state. But during her recruitment visit, an informal gathering with students from the all-inclusive University of Utah SACNAS (Society for Chicanos/Hispanics and Native Americans in Science) chapter helped her see things differently. After talking with them, she knew that if she came, she would be surrounded by a supportive community. She chose the U, and three years later, that prediction has held true.

To me, SACNAS is a community away from home, says Bowman, now president of the U chapter. Its a place that has created a sense of belonging for me on campus while helping me to achieve my professional goals.

Bowmans experience isnt unique. The bioscience graduate programs have collaborated with the U SACNAS community in its annual recruitment activities since 2017. These efforts, which included hosting the 2017 SACNAS National Conference in Salt Lake City, have resulted in tripling recruitment of students from historically underrepresented (UR) backgrounds. UR students now comprise 33% of the domestic class, and racial and ethnic minorities comprise 28%, reflecting the national talent pool.

Knowing this diverse, all-inclusive community is here helps recruits decide, in parallel to the awesome research, that we are their best fit, says Jeanette Ducut-Sigala, U SACNAS manager.

The ability to make meaningful change in diversity and inclusion has earned U SACNAS national recognition. In a virtual ceremony held on Oct. 13, the national organization designated the U group Chapter of the Year along with six other local chapters of the 133 located in the U.S. and Puerto Rico.

U SACNAS officially launched in 2014 with the goal of training and supporting the next generation of diverse STEM talent. From students to professionals, the parent organization fosters success in attaining advanced degrees, careers and positions of leadership within STEM. The U chapter mainly serves graduate students, postdocs and staff while a sub-chapter centered on main campus is open to both undergraduates and graduate students. Ducut-Sigala, biochemistry faculty Minna Roh-Johnson and Paul Sigala and human genetics faculty Clement Chow operate as advisors.

Its clear that across the country there is a great need for organizations like this one. According to SACNAS, the national STEM workforce is only 6% Hispanic, 4.8% Black, and 0.2% Native American, numbers that are significantly lower than in the overall U.S. workforce. A lack of diversity hurts all of us, the organization explains, because diverse voices bring creative solutions to our worlds most pressing scientific problems.

U of U SACNAS helps its members to grow through authentic inclusion: hosting talks by professionals to inspire career aspirations and create connections with role models, supportive peer mentoring, outreach and leadership development. In collaboration with the University Counseling Center, Health and Wellness Center and Center for Student Wellness, they hold sessions where members can talk through troublesome issues and learn strategies for balancing their lives in and outside of science. Knowing that role modeling can make all the difference, particularly in young children, they also perform outreach with local K-12 schools to show that science is for everyone.

The organization has provided a sense of belonging to member Jesse Velasco-Silva, a biochemistry graduate student and the chapters vice president. The SACNASfamiliaalways encourages me to bring, show and celebrate my strength, resilience, culture, traditions and science, he says. He explains that being a first-generation Mexican-American immigrant and college student has come with challenges. The guidance and support hes received from the SACNAS community has helped him to overcome them.

As for Bowman, her experience has come full circle. She benefitted from the openness of the U SACNAS community when she was making the difficult decision of where to get her doctoral degree. Now, she does the same for the next sets of prospective students.

I get to show the recruits, particularly the first-gen BIPOC students, how we belong on campus, belong in our programs, and thrive here because we have a community like SACNAS, she says. We have a supportive, collaborative environment at Utah and really, a university committed to equity and inclusion.

Read the original:
Changing the face of science | @theU - @theU

Abstract

The results of multiple studies have shown that a substantial proportion of men with advanced prostate cancer carry germline DNA repair mutations. Germline testing in prostate cancer may inform treatment decisions and consideration for clinical trials. There are 2 FDA approved PARP inhibitors (PARPi), olaparib (Lynparza) and rucaparib (Rubraca), for the treatment of advanced prostate cancer with DNA repair deficiency. Increasing demand for germline testing in prostate cancer and a shortage of genetic counselors have created a need for alternative care models and encouraged oncologists to take a more active role in performing germline testing. This article summarizes recommendations for germline testing in prostate cancer and describes care models for providing counseling and testing.

Genetic testing in men with prostate cancer has become more widespread since the discovery that men with metastatic prostate cancer are more likely to carry germline DNA repair gene mutations and the approval of PARP, or poly adenosine diphosphate-ribose polymerase, inhibitors (PARPi) for prostate tumors with DNA repair deficiency. The resulting substantial increase in men with prostate cancer who are eligible for germline testing, with time-sensitive treatment implications, challenges the traditional in-person, time- and resource-intensive cancer genetics care delivery model, and calls for alternative approaches. Urologists, oncologists, and other medical providers are encouraged to take a more active role in delivering germline testing, and they should be aware of current guidelines and optimal pretest and posttest counseling components. This article focuses on the implementation of germline testing in the care of patients with prostate cancer.

Germline genetic testing evaluates for inherited mutations (otherwise known as pathogenic or likely pathogenic variants) that are found in virtually all cells of the body and are derived from the fundamental DNA of an individual. DNA from no cancerous, healthy cells (eg, leucocyte or saliva/buccal swab cells) are used for germline genetic testing. The goals of germline genetic testing are to evaluate for an inherited cancer syndrome; to inform individual and family cancer risks; and to guide cancer prognosis and treatment decisions. Germline testing should be distinguished from recreational and somatic (tumor-specific) testing. Direct-to-consumer recreational genetic testing consists of an at-home test that is advertised to help understand the customers ancestry. Recreational genetic panels look for inherited variants in saliva/buccal swab cells to inform genealogy, and they are not primarily intended to guide medical decisions as they lack gene coverage and clinical-grade precision. None of the recreational genetic tests include a comprehensive assessment of the BRCA1/2 or other DNA damage repair genes and are inadequate for medical purposes. Somatic testing panels are designed to identify alterations in a tumors DNA. A somatic test may occasionally identify mutations expected to be germline, in which case follow-up dedicated germline tests are needed. Examples of somatic panels that report germline mutations include Tempus and UW-Oncoplex. However, many somatic panels use bioinformatics algorithms that may filter out, miss, and/or choose not to report germline mutations. Thus, in general, somatic panels should not be considered adequate for germline conclusions; at most, they should prompt confirmatory germline testing. This articlefocuses on dedicated clinical-grade germline testing.

Germline testing in men with prostate cancer is being performed more often since an important number of prostate cancer cases have a heritable component.1,2 Germline mutations in DNA repair genes, such as BRCA1/2, contribute to hereditary prostate cancer risk and are present in up to 11.8% of men with metastatic prostate cancer,3 compared with 4.6% among men with localized prostate cancer and 2.7% in persons without a known cancer diagnosis.3,4

Germline BRCA1/2 mutations are associated with increased risk of prostate cancer: up to a 3.8-fold increase with BRCA1 and an 8.6-fold increase with BRCA2 mutations.5 Men who carry germline BRCA1/2 mutations are not only at increased risk of developing prostate cancer but are also at risk of a more aggressive prostate cancer phenotype. In their study, Castro et al found that patients with prostate cancer with germline BRCA1/2 mutations at the time of diagnosis were more likely to have higher Gleason score (8) and more advanced stage (T3/4, nodal involvement, and metastases) compared with noncarriers. Men with germline BRCA1/2 mutations also had shorter cancer-specific survival (CSS) than noncarriers (15.7 vs 8.6 years; P=.015).6 Men with localized prostate cancer and germline BRCA1/2 mutations have worse outcomes after definitive treatment with surgery or radiation compared with noncarriers: 5-year metastasis-free survival, 72% vs 94%; P <.001; 5-year CSS, 76% vs 97%; P <.001.7 The prospective PROREPAIR-B study found that germline BRCA2 status is an independent prognostic factor for CSS in patients with metastatic castration-resistant prostate cancer (mCRPC; 17.4 vs 33.2 months; P = .027).8

Based on the study results above and others, the current National Comprehensive Cancer Network (NCCN) guidelines for prostate cancer (version 1.2022)9 recommend germline testing for the subsets of patients with prostate cancer who are more likely to have germline DNA repair mutations (Figure 1).

The NCCN guidelines recommend offeringgermline testing to the following groups of patients with prostate cancer9:

I. Men with node positive, high-risk or very highrisk localized prostate cancer

II. Men with metastatic prostate cancer

III. Men meeting family history criteria (Table 1)

NCCN recommends considering germline testing for men with personal history of prostate cancer and:

I. intermediate risk prostate cancer and intraductal/cribriform histology

II. personal history of exocrine pancreatic, colorectal, gastric, melanoma, pancreatic, upper tract urothelial, glioblastoma, biliary tract or small intestinal cancers

Several commercial vendors provide germline testing panels, including Invitae, Color, and Ambry. Further details and information on available panels can be found on the vendors websites. Panel sizes vary from dedicated BRCA1/2 testing to 91-gene panels. The NCCN guidelines for prostate cancer9 recommend that germline testing panels include genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2).9,10 Broader panels might be appropriate for men with mCRPC, especially if clinical trial participation is being considered. Average turnaround time for germline testing is between 10 and 30 days, which varies depending on the particular panel. The cost of germline testing varies depending on insurance coverage. Some companies offer provide testing for a flat out-of-pocket fee (eg, $250), and a benefit of participating in certain research studies may be no-cost testing.

NCCN guidelines recommend germline testing for a large subset of patients with prostate cancer, but the best care model to offer education and testing is unclear. The traditional clinical care delivery model for cancer genetics includes 2 in-person visits with a genetic counselor, the first for pretest risk assessment and education and the second to discuss the results. This is the most established pathway and, historically, has been utilized the most. However, broadening recommendations for germline testing create great demand that cannot be currently met in a timely fashion by the approximately 4000 genetic counselors in the United States.11,12 Therefore, oncologists and other providers are increasingly performing pretest counseling, ordering genetic testing, and providing posttest counseling for their patients, or following hybrid models (Table 2).13

The provider-led germline testing model has been tested in breast and ovarian cancer but is new in prostate cancer.14-18 Scheinberg et al reported results of a multicenter prospective study evaluating provider-led germline testing for men with prostate cancer. Twelve oncologists received training about the role of germline testing and in counseling patients, and then offered germline testing to patients with mCRPC in their practice. Those patients who accepted germline testing received pretest counseling and educational materials, and later discussed test results in the oncologists office. If a germline mutation was identified, the patient was referred to a genetic counselor to discuss the further implications of the results and to initiate cascade testing. Most patients (63 of 66; 95%) accepted the germline testing and high satisfaction rates were achieved among both oncologists and patients.19 A provider-led germline testing model in the Veterans Affairs health care system was also evaluated. Patients with metastatic prostate cancer were offered germline testing by their oncologists during regular clinic visits. Pretest counseling was provided by oncologists and study coordinators and saliva for the test was collected in the clinic. Posttest counseling sessions with genetic counselors were provided over the phone by the testing panel company. Again, most patients (190 of 227 approached veterans; 84%) accepted testing, and the test completion rate was 80% (182/227).20 Results of early studies suggest that provider-led germline testing in prostate cancer could be effective and satisfactory for both patients and providers.

The need to streamline germline testing also calls for the utilization of new technologies, such as video- or phone-based counseling. The EMPOWER study (NCT04598698) assessed mens preference of in-person genetic counseling vs video-based genetic education21; results indicated that in-person genetic counseling was preferred by men with less education and higher anxiety levels, and it resulted in greater improvement of cancer genetics knowledge. The rates of genetic testing uptake were similar for video-based and in-personcounseling groups.21 Video-based counseling was also evaluated by Tong et al, who compared 2 models of streamlined germline testing in prostate cancer: (a) a take-home genetic kit provided by an oncologist, followed by referral to a genetic counselor if subsequent results are concerning; and (b) a genetic testing station, at which the patient participated in a video call from a genetic counseling assistant for genetics education and collection of family history, which was followed by saliva sample collection and, later, referral to a genetic counselor if any mutation was identified. The latter approach resulted in a lower rate of incomplete tests and a higher rate of follow-up with genetic counselors for positive results. Authors suggested that utilization of video education and involvement of genetic counselor assistants may improve access to germline testing among patients with prostate cancer.22 Several studies are ongoing to evaluate other care models to provide genetic testing in prostate cancer (eg, NCT02917798, NCT03076242, NCT03328091, NCT03503097).23

Oncologists who choose to perform germline testing need to be comfortable with several aspects of genetic counseling and to remain current on the ethics of informed consent and posttest counseling for germline testing (Figure 2). The 2019 Philadelphia Prostate Cancer Consensus Conference suggests that optimal pretest consent should include discussion of the purpose of testing, types of possible results (ie, pathogenic/likely pathogenic; benign/likely benign; variant of unknown significance; no variants identified), the possibility of identifying hereditary cancer syndrome and/or other cancer risks, testings potential cost, the importance of cascade family testing, and the Genetic Information Nondiscrimination Act (GINA) law.12 The GINA law protects against discrimination based on genetics in employment and health insurance; however, it is not applicable to life insurance, long-term care disability insurance, Indian Health services, and patients enrolled into federal employee, Veterans Administration, and US military health benefit plans.23,24 These gaps in protection by GINA law are important to discuss with patients, who may need to consider them before proceeding with the germline testing. Providers should also consider discussing the different panels available for testing, the privacy of genetic tests, and genetic laboratories policies related to sharing and selling of data.12

Providers ordering germline tests also must accept responsibility to follow up with patients if reclassification occurs of a variant of (currently) unknown significance (VUS). VUS are reported in about 30% of men with prostate cancer who undergo germline testing.4 VUS results do not change clinical recommendations, and the majority of them end up being reclassified as benign.25,26 In the Find My Variant Study, 38 of 63 VUS (61%) were reclassified: 32 of 38 (84%) as benign/likely benign and 6 of 38 (16%) as pathogenic/likely pathogenic.27,28 In the rare case when a VUS is reclassified as pathogenic or likely pathogenic, the provider who ordered the test is notified and they are responsible for disclosing the reclassification to the patient. Regardless of the model used, genetic counselor referral is recommended if a patient has a germline mutation identified and/or if clinical suspicion is high for an inherited cancer predisposition. Collaborative efforts are needed to educate oncology providers on aspects of germline testing counseling and to create shared printed and video resources for patients to facilitate informed consent.

Germline testing in men with prostate cancer can potentially benefit not only the patient but also family members. If a germline mutation is identified in a patient, testing for the same mutation in family members (cascade testing) should be performed. For instance, identifying family members with BRCA1/2 mutations could inform potentially lifesaving risk-reducing interventions, eg, prophylactic salpingo-oophorectomy for female BRCA1 mutation carriers. The IMPACT study (Identification of Men with a Genetic Predisposition to Prostate Cancer: Targeted screening ingBRCA1/2mutation carriers and controls) evaluated the utility of prostate-specific antigen (PSA) screening in men aged 40 to 69 years with germline BRCA1/2 mutations compared with its utility in noncarriers.29,30 The study enrolled 3027 men with no personal history of prostate cancer: 919 BRCA1 carriers, 902 BRCA2 carriers, 709 BRCA1 noncarriers, and 497 BRCA2 noncarriers. Preliminary results, reported after 3 years of follow-up, showed that BRCA2 mutation carriers, compared with noncarriers, have a higher incidence of prostate cancer and a younger age of diagnosis. The results for BRCA1 carriers were not definitive, and further investigation is needed. The results from IMPACT suggest annual PSA screening for BRCA2 mutation carriers aged between 40 and 69 years, using PSA cutoff of 3.0 ng/ml.30 Studies evaluating the predictive value of lower PSA cutoff and prostate MRI are ongoing (eg, NCT03805919, NCT01990521).

Advanced disease

PARPi. Patients with DNA repair mutations have higher responserates toPARPiand platinum chemotherapy.31,32 In 2020, two PARPi received FDA approval for treatment of mCRPC with germline or somatic DNA damage repair gene mutations. Rucaparib was approved based on the phase 2 TRITON2 (NCT02952534) study; it reported a 51% (50/98) radiographic response rate among men with mCRPC and BRCA1/2 alterations.33 The benefit for men with non-BRCA DNA repair mutations was less clear, and rucaparib is currently approved only for carriers of BRCA1/2 mutations. 33-35 The olaparib label includes a larger number of mutated genes eligible for treatment (BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L), based on results of the phase 3 ProFOUND study (NCT02987543). ProFOUND compared olaparib with enzalutamide or abiraterone and showed improved radiographic progression-free survival (5.8 months vs 3.5 months) with olaparib. 36 Several other ongoing studies are evaluating the efficiency of PARPi monotherapy and combined therapies in mCRPC. Table 3 summarizes study results reporting response rates to PARPi in prostate cancer. 37

Platinum chemotherapy. Historically, platinum chemotherapy has been used to treat tumors, such as ovarian or pancreatic cancer, that have a high frequency of DNA repair mutations.38,39 Early data suggest that platinum chemotherapy is also effective in prostate tumors with DNA repair deficiency.40-43 A retrospective case series by Cheng et al showed that 3 of 3 patients with prostate cancer who had biallelic inactivation of BRCA2 had an exceptional response to platinum chemotherapy after progressing on several therapies.40 The results of a larger retrospective study supported this observation, reporting that 75% (6/8) of patients with mCRPC and withgermline BRCA2 mutations had a PSA50 response (ie, decline of prostate-specific antigen by 50% from baseline) to platinum chemotherapy compared with 17% (23/133) of mCRPC patients without gBRCA2 mutations.41 Mota et al reported a 53% (8/15) PSA50 response to platinum chemotherapy among men with mCRPC and DNA damage repair mutations (ie, BRCA2, BRCA1, ATM, PALB2, FANCA, and CDK12).43

NCCN guidelines recommend considering DNA repair mutation status when discussing the possibility of active surveillance. Germline mutations in BRCA1/2 or ATM are associated with a higher likelihood of grade reclassification among men undergoing active surveillance.44 Mutation carriers should be closely monitored; they could potentially benefit from an earlier definitive treatment approach.

BRCA1/2 carriers have worse outcomes with conventional definitive therapies. Castro et al evaluated the response of BRCA1/2 carriers with localized prostate cancer to 2 radical treatmentsdefinitive radiation and radical prostatectomyand reported that BRCA status is an independent prognostic factor for metastasis-free survival (HR, 2.36; P = .002) and CSS (HR, 2.17; P = .016).7 New treatment approaches in earlier disease stages are being evaluated in clinical trials for patients with prostate cancer and DNA repair deficiency. Targeted therapies, such as PARPi, are being actively investigated in the biochemically recurrent stage of prostate cancer (eg, NCT03047135, NCT03810105, NCT04336943, NCT0353394) and as neoadjuvant therapy in localized disease (eg, NCT04030559).

Germline testing is becoming more commonplace with advances in precision oncology and expanding treatment implications of the results of this testing. The NCCN prostate cancer guidelines recommend germline testing for men with high-risk or very highrisk localized prostate cancer; men with metastatic prostate cancer; patients with intraductal histology of the prostate; and patients meeting family history criteria. These recommendations have created a need for germline testing of many prostate cancer patients, which calls for a change in the traditional cancer genetics delivery model to meet the new demand.45 Oncologists are encouraged to take a more active role in performing germline testing, but the optimal approach is unclear. Until the results of larger trials focusing on various testing delivery models are available, joint efforts are needed to build collaborative relationships between oncologists and genetic specialists. Further efforts are required to create dedicated resources to support providers in this new era of genetic testing and precision oncology in prostate cancer, which is marked by near-constant change.

ACKNOWLEDGMENTS: We gratefully acknowledge support from the Institute for Prostate Cancer Research, NIH/NCI CCSG P30CA015704, NIH SPORE CA097186, NCI T32CA009515 award, Congressional Designated Medical Research Program (CDMRP) award W81XWH-17-2-0043, and the Prostate Cancer Foundation.

Conflict of interest/disclosures: AOS has no conflicts to disclose; HHC receives research funding to her institution fromClovis Oncology, Color Genomics, Janssen Pharmaceuticals, Medivation, Inc. (Astellas Pharma Inc), Phosplatin Therapuetics, and Sanofi S.A., and has a consulting or advisory role withAstraZeneca.

Sokolova is from the Division of Medical Oncology at Oregon Health Science University (OHSU) and the OHSU Knight Cancer Institute.

Cheng is from the Division of Medical Oncology at the University of Washington and the Division of Clinical Research at Fred Hutch Cancer Research Center.

1. Mucci LA, Hjelmborg JB, Harris JR, et al; Nordic Twin Study of Cancer (NorTwinCan) Collaboration. Familial risk and heritability of cancer among twins in Nordic countries. JAMA. 2016;315(1):68-76. doi:10.1001/jama.2015.17703

2. Hjelmborg JB, Scheike T, Holst K, et al. The heritability of prostate cancer in the Nordic Twin Study of Cancer. Cancer Epidemiol Biomark Prev. 2014;23(11):2303-2310. doi:10.1158/1055-9965.EPI-13-0568

3. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443-453. doi:10.1056/NEJMoa1603144

4. Nicolosi P, Ledet E, Yang S, et al. Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines. JAMA Oncol. 2019;5(4):523-528. doi:10.1001/jamaoncol.2018.6760

5. Giri VN, Beebe-Dimmer JL. Familial prostate cancer. Semin Oncol. 2016;43(5):560-565. doi:10.1053/j.seminoncol.2016.08.001

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7. Castro E, Goh C, Leongamornlert D, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol. 2015;68(2):186-193. doi:10.1016/j.eururo.2014.10.022

8. Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490-503. doi:10.1200/JCO.18.00358

9. NCCN Clinical Practice Guidelines in Oncology. Prostate cancer, version 1.2022. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed 9/10/2021

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11. Abacan MA, Alsubaie L, Barlow-Stewart K, et al. The global state of the genetic counseling profession. Eur J Hum Genet. 2019;27(2):183-197. doi:10.1038/s41431-018-0252-x

12. Giri VN, Knudsen KE, Kelly WK, et al. Implementation of germline testing for prostate cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol. 2020;38(24):2798-2811. doi:10.1200/JCO.20.00046

13. Giri VN, Hyatt C, Gomella LG. Germline testing for men with prostate cancer: navigating an expanding new world of genetic evaluation for precision therapy and precision management. J Clin Oncol. 2019;37(17):1455-1459. doi:10.1200/JCO.18.02181

14. George A, Riddell D, Seal S, et al. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Sci Rep. 2016;6:29506. doi:10.1038/srep29506

15. Yoon SY, Bashah NSAhmad, Wong SW, et al. LBA4_PR. Mainstreaming genetic counselling for genetic testing of BRCA1 and BRCA2 in ovarian cancer patients in Malaysia (MaGiC study). Ann Oncol. 2017;28(suppl 10):x187. doi:10.1093/annonc/mdx729.004

16. Enomoto T, Aoki D, Hattori K, et al. The first Japanese nationwide multicenter study of BRCA mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of BRCA (CHARLOTTE). Int J Gynecol Cancer. 2019;29(6):1043-1049. doi:10.1136/ijgc-2019-000384

17. Kemp Z, Turnbull A, Yost S, et al. Evaluation of cancer-based criteria for use in mainstream BRCA1 and BRCA2 genetic testing in patients with breast cancer. JAMA Netw Open. 2019;2(5):e194428. doi:10.1001/jamanetworkopen.2019.4428

18. Colombo N, Huang G, Scambia G, et al. Evaluation of a streamlined oncologist-led BRCA mutation testing and counseling model for patients with ovarian cancer. J Clin Oncol. 2018;36(13):1300-1307. doi:10.1200/JCO.2017.76.2781

19. Scheinberg T, Goodwin A, Ip E, et al. Evaluation of a mainstream model of genetic testing for men with prostate cancer. JCO Oncol Pract. 2021;17(2):e204-e216. doi:10.1200/OP.20.00399

20. Sokolova A, Cheng HH, Montgomery B. Implementation of systematic germline genetic testing (GT) for metastatic prostate cancer (mPC) patients at the Puget Sound VA Prostate Oncology Clinic. J Clin Oncol. 2020;38(15 suppl):abstr 1578. doi:10.1200/JCO.2020.38.15_suppl.1578

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Germline Testing in Prostate Cancer: When and Who to Test - Cancer Network

By 2050, 13.5 million people in the United States will live with Alzheimers disease unless early diagnosis and treatment can delay the onset of the disease. Current treatment centers around slowing the progression of the disease.

In the journal EMBO Molecular Medicine, scientists revealed this week that circulating microscopic nucleotides assembled amino acids that bind directly to messenger ribonucleic acids (mRNAs) can identify cellular imbalance in the brain. These nucleotides, called microRNAs, are easily measured blood proteins that may identify the early risk of Alzheimers disease.

The role of these microRNAs in directing mRNAs to protect the brain from inflammation means that targeting them for therapy could inhibit cellular damage in the brain and delay the onset of dementia.

Verna R. Porter, M.D., commented on the pivotal aspects of this research for Medical News Today. Dr. Porter is a neurologist and the director of programs for dementia, Alzheimers disease, and neurocognitive disorders at Providence Saint Johns Health Center in Santa Monica, CA.

Alzheimers disease is usually diagnosed at a relatively advanced/symptomatic stage of the disease with relatively advanced biomarker/molecular pathology for example, the amyloid deposit in the brain is already well-established. The problem has been that by the time the disease is diagnosed, the current treatments have been essentially ineffective in terms of disease modification.

Dr. Verna R. Porter

The molecular brain changes linked to Alzheimers disease often occur many years before those affected manifest clinical symptoms. Therefore, these researchers designed a model to compare biomarker results in healthy adults with those in people with cognitive decline.

In a multifaceted study, based on the similarities between human and murine neurophysiology, research scientists scored young people aged below 30 years for cognitive function. Then, they identified microRNAs present in the blood that matched their cognitive function. Finally, the scientists linked these microRNAs to larger mRNAs associated with cognitive decline.

Once the researchers had made this connection, they studied microRNAs as possible biomarkers for early cognitive decline.

Aging mice can develop cognitive decline, similar to humans. Therefore, the researchers designed a follow-up experiment measuring these same biomarkers in healthy and aging mice. The scientists could now study the before and after of these microRNA biomarkers, looking for their presence in the blood of both mice that were healthy and those that had cognitive decline.

Dr. Islam, Prof. Fischer, and colleagues from the German Center for Neurodegenerative Diseases and the University Medical Center in Gttingen, Germany, found seven microRNAs frequently linked to age-related cognitive decline in mice. They then correlated these microRNAs to their known functions in human genes, which genome-wide association studies (GWAS) had identified.

The scientists compared their mouse microRNA results with the 709 human genes related to cognitive function in healthy individuals. Three microRNAs that regulate genes in cognitively impaired mice were repeatedly linked to crucial genes in human cognitive function.

To further support their results, the researchers imposed the three microRNAs onto cell cultures of the murine hippocampus, a part of the brain responsible for memory. They confirmed that increased expression of these three microRNAs (directing mRNAs) in cell culture impaired neural function and plasticity the ability of nerves to modify themselves in response to experience and injury.

The scientists then directly measured the three microRNAs present in the brains of cognitively impaired mice and found high levels. Finally, they compared their results with those of prior studies, tentatively linking these microRNAs to neuroinflammation and cellular stress. Dr. Porter summarized:

These researchers noted that circulating microRNAs are linked to cognitive function in young/healthy individuals. Using mouse models, these researchers have identified circulating three-microRNA signatures in the blood, which are increased in patients with mild cognitive impairment (MCI) and suggest an enhanced risk of future conversion from MCI to [Alzheimers disease].

In mice, high levels of the three microRNAs correlated with cognitive decline. But is it possible to extrapolate these results to humans? And could the amount of the three microRNAs predict cognitive impairment before clinical signs of dementia appear?

The researchers studied participants from different age groups in cross-sectional settings. First, they analyzed the plasma of individuals with MCI. In comparison with cognitively healthy people, those living with MCI had significantly increased levels of the microRNAs.

The scientists wondered whether the three microRNAs were higher in people with MCI who go on to develop Alzheimers disease. By analyzing past blood samples, they learned that people with higher levels of the three microRNAs were more likely to progress from stable MCI to Alzheimers disease than those with lower levels.

They also measured the microRNAs in the cerebrospinal fluid of people living with MCI and found significantly elevated levels.

Proposing possible mechanisms in humans, the researchers studied human brain cell cultures, treating them with the three microRNAs. Similar to the previously studied mouse brain cell cultures, they found decreased neuronal synaptic function and increased cellular stress.

So, can we intervene in the function of these elevated three microRNAs and reverse brain cell damage?

The answer is maybe. To test this, the scientists developed an inhibitor of each of the three microRNAs. They injected the three microRNA inhibitors (anti-miRs) into mice with Alzheimers-like pathology, finding that this improved the animals performance in hippocampal-dependent learning strategies, such as escaping from a water maze.

The therapeutic hope is that by targeting these early biomarkers of disease (i.e., targeting all three microRNAs using anti-miRs), we may be able to ameliorate cognitive decline in humans, as has been shown using mouse models.

Dr. Verna R. Porter

The researchers acknowledge that many other complex risk factors likely play a role in Alzheimers disease. Due to this, highly effective therapy may require the regulation of several molecular processes.

MNT queried Dr. Porter on why treatments dealing with the onset of Alzheimers disease have been so elusive. Dr. Porter described how researchers have rigorously studied a protein deposit in the brain, called beta-amyloid, as a potential cause of Alzheimers disease. It seems that beta-amyloid accumulation in the brain may interfere with communication between brain cells in people living with Alzheimers disease. She recounted:

A great deal of research effort has been focused on the amyloid cascade hypothesis of [Alzheimers disease] pathology. The numerous clinical trial failures, utilizing various anti-amyloid therapeutic interventions, have been very disappointing []. It has been suggested that the numerous failed clinical trials that have largely focused on beta-amyloid deposits [indicate] that beta-amyloid may not be the main driver of the disease.

Instead, (the) deposition of beta-amyloid in the brain may be a biological response to some other potential trigger. In this view, beta-amyloid deposits would represent residual scars (after-effects) like the scar that seals a wound, rather than the primary driving process of the disease. It may be that anti-amyloid therapies are simply administered too late in the disease progression.

Newer research is looking more broadly at other potential driving factors of the disease, such as tau protein deposition, and the potential preventive role of lifestyle modifications for example, diet, nutrition, exercise, sleep, and appropriate supplements as another potential way forward in the prevention of the disease.

Tau is a protein involved in brain cell stabilization. In some people living with Alzheimers disease, it is dysfunctional, causing neurofibrillary tangles and disturbing synaptic communication between neurons.

The most promising result of the new study is that the three microRNAs appear to be a suitable, minimally invasive biomarker. They are also easy to measure in routine blood samples even in a finger prick. Moreover, the data support that this three-microRNA-signature test could be a first step in helping detect individuals at risk of cognitive disease.

For people living with cognitive decline, early detection may increase their chances of successful therapeutic intervention with existing treatment or future novel RNA-based approaches targeting the three-microRNA signature.

In conclusion, Dr. Porter noted to MNT:

Presently, there is an urgent need for molecular biomarkers that are minimally invasive, able to detect an individual at risk of developing disease, and [able to] detect biomarkers of disease as early as possible even in the setting of multiple disease pathologies, e.g., mixed Alzheimers and vascular pathology. The hope is that simple approaches, such as a blood test, could be applicable in the context of routine screening approaches with the [aim] of identifying individuals at risk for developing Alzheimers disease, who could then undergo further diagnostic/confirmatory evaluations.

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Dementia: Early biomarkers in the blood may predict cognitive decline - Medical News Today

Some people get severely sick with COVID-19. Others don't even notice they've caught the infection.

Understanding the role of genetic variants in infection outcomes could help prevent or treat infectious diseases by restoring deficient immunity.

Over the past months, several studies have shown that some genes are potentially involved in the congenital resistance some people have towards COVID-19.

Blood types and COVID resistance

For example, the authors wrote that evidence suggested that people with O type blood groups may be slightly more resistant than people with other blood types.

In vitro studies have identified candidate genes that might be involved in how SARS-CoV2 enters human cells and triggers the infection.

SARS-CoV-2 penetrates human cells by binding the ACE2 receptor, which sits in the cell's membrane.

Scientists have discovered that a rare variant located close to ACE2 confers protection against COVID-19.

The hypothesis is that the variant decreases ACE2 expression.

In other in vitro studies, scientists found that some human ACE2 polymorphisms (a gene is polymorphic if more than one allele occupies that gene's locus) bind the SARS-CoV-2 spike protein with different affinities.

The role of genetic variants

Historically, therapeutics for infectious diseases have focused primarily on the pathogen rather than the host.

The most common idea has been to prevent the disease by vaccinating against the pathogen or stop the infection by interfering with the pathogen using drugs.

Understanding the role of genetic variants in infection outcomes could help prevent or treat infectious diseases by restoring deficient immunity.

"These variants are of particular interest for two reasons," the authors wrote.

"First, they can provide a deep understanding of the essential biological pathways involved in infection with SARS-CoV-2.

Second, they will allow for the development of innovative therapeutic interventions to prevent or treat SARS-CoV-2 infection in others."

The proof of principle for this second reason has been provided by CCR5 - a genetic mutation occurring in roughly one per cent of the population, which prevents HIV from binding to the surface of white blood cells.

Medicine mimicking genetics

After discovering CCR5, scientists developed an anti-retroviral drug called maraviroc, which mimics the effect of the mutation.

"No specific drug effective against COVID-19 has been discovered since the start of the pandemic," the authors wrote.

"Lessons learned [from genetics] could potentially guide us toward such specific treatments for COVID-19."

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A lucky few are unusually resistant to COVID-19. Scientists are trying to find a reason in their genes. - Mandurah Mail

Rochelle dos Santos embraces her daughter, who was born with microcephaly in 2016 after dos Santos contracted Zika during her pregnancy in midwest Brazil. Ueslie Marcilino/Undark Magazine hide caption

Rochelle dos Santos embraces her daughter, who was born with microcephaly in 2016 after dos Santos contracted Zika during her pregnancy in midwest Brazil.

Rochelle dos Santos learned that her daughter would probably be born with microcephaly a condition where a baby's head is much smaller than expected when she was seven months pregnant. It was 2016 and Brazil was going through an unprecedented microcephaly outbreak associated with the mosquito-borne virus Zika. After the baby was born and the diagnosis of congenital Zika syndrome was confirmed, several researchers approached dos Santos to see if she'd join relevant clinical studies. Eager to understand her daughter's condition, she agreed.

Dos Santos says she was surprised to learn through a social media post last year that an international study that she participated in had been published in the journal Brain & Development. The study took over a year to be completed, and dos Santos had taken her daughter multiple times to the hospital for evaluations. As the head of an association for families of children affected by Zika in Gois state in midwest Brazil, dos Santos wanted to share the findings with the other caregivers. She says she had to reach out directly to Hlio van der Linden, a neurologist at the Dr. Henrique Santillo State Center for Rehabilitation and Readaptation who authored the study in partnership with researchers in Brazil and the United States, to ask that a copy be shared with her. But she says he told her there was no point because it was written in English.

"Of course, we get upset," she recalled in her native Portuguese. "We want to have this feedback and better understand this situation that is new for everyone." Dos Santos who noted that while she speaks only a little English, her husband reads and speaks English capably said she feels used and that many other families share the same sentiment. "We know that COVID is now the priority," dos Santos adds, "but our children are still here, they still have needs."

The study's author sent her the article, and dos Santos says her husband translated it for her though she adds that she was also asked by van der Linden not to share it. (Van der Linden told Undark by email that while he did point out to dos Santos that the article was written in English, his main concern was running afoul of the journal's publishing rules. His request not to share it, he added, was for social media posts. "There was no problem in sharing the article with other mothers," he wrote, "but I believe this wasn't clear to the mother of the patient.")

Children with congenital Zika syndrome face numerous health issues, all originating from the peculiar way in which Zika attacks the developing brain. In addition to the condition's most pronounced feature reduced head size many have rigid muscles, difficulty swallowing and breathing and problems with the retina and optic nerve, as well as other symptoms that emerge as the children grow. "The doctors say that only time will tell how our children will be tomorrow," dos Santos says, "because there are no adults with this syndrome."

Dos Santos is not the only caregiver who felt left behind by scientists. Family groups like the one she heads have sprung up across the country, and members are increasingly at odds with the scientists who have used their children for research. The grandmother and caretaker of a boy with congenital Zika syndrome, Alessandra Hora dos Santos (no relation to Rochelle), launched one of these associations in Alagoas state in northeast Brazil in 2017. She says that lately she has been declining requests to participate in new studies although such invitations are becoming rare because there haven't been new outbreaks of the syndrome since 2016 and she noticed that other families are doing the same.

Scientists who conducted the studies on Zika during the peak and the aftermath of the outbreak admit that communicating the results to families is not always effective, and that it was not the top priority during the Zika crisis. In the rush to collect data, not all researchers took the time to explain in detail what their projects were about and set clear expectations. Busy caretakers, on the other hand, were hardly able to carefully read the informed consent forms they were signing to authorize investigators to collect data from their children. Over the last few years, these families have demanded to participate more actively in the scientific discussion around Zika.

"We feel diminished," says Alessandra Hora dos Santos. "It's like we were lab rats. They come in nicely, collect information, collect exams on the child, and in the end, we don't know of any results. It's like we are being used without even knowing why that is being done."

Left: Dos Santos helps her daughter, pictured, with physical therapy. Many children with congenital Zika disorder are physically disabled. Right: Due to difficulties swallowing, dos Santos' daughter uses a feeding tube, which is attached to her wheelchair. Ueslie Marcilino/Undark Magazine hide caption

Left: Dos Santos helps her daughter, pictured, with physical therapy. Many children with congenital Zika disorder are physically disabled. Right: Due to difficulties swallowing, dos Santos' daughter uses a feeding tube, which is attached to her wheelchair.

Left: Dos Santos' daughter uses leg braces to help her stand. Other symptoms of the disorder emerge as children grow. Right: Dos Santos guides her daughter to create a finger painting. "Our children are still here, they still have needs," she says. Ueslie Marcilino/Undark Magazine hide caption

Left: Dos Santos' daughter uses leg braces to help her stand. Other symptoms of the disorder emerge as children grow. Right: Dos Santos guides her daughter to create a finger painting. "Our children are still here, they still have needs," she says.

By the time physicians started to notice a surge in microcephaly in Brazil in mid-2015, researchers had to scramble to design studies, get funding and conduct analyses. Eventually, scientists from multiple institutions coalesced in the Microcephaly Epidemic Research Group (MERG). They began the research efforts even before the link with Zika had been established and had a crucial role in guiding public health strategies to tackle the epidemic. "There was a lot of pressure coming from the media and the health ministry," says infectious disease expert Demcrito de Barros Miranda-Filho, a member of MERG and a professor at the University of Pernambuco. "We had to develop all the projects from scratch and submit them to the ethics committees within a deadline," he says, adding that there was also pressure to give answers to the families.

One of the group's concerns was to immediately share individual results of tests and clinical evaluations that could directly impact the child's treatment. But when it comes to the general findings at the end of the study, says Miranda-Filho, the researchers didn't properly communicate them to the participants.

"It is very complex to decode biological questions and put them into a more understandable language," says Thlia Velho Barreto de Arajo, an epidemiologist at the Federal University of Pernambuco and a member of MERG. "We haven't figured out a way to do that yet, and we would need research resources to get advice for transforming technical language into something palatable." Ricardo Arraes de Alencar Ximenes, an epidemiologist at both the University of Pernambuco and the Federal University of Pernambuco, notes that one of the obstacles to develop well-thought-out communication strategies is getting dedicated funding.

Physician Camila Ventura, one of the coordinators of an ambitious project with the goal of evaluating the neurodevelopment of about 200 children with congenital Zika syndrome over five years, says she is familiar with the families' demands and agrees with them. But there are other obstacles beyond adequate funding, she says. For example, with funding from the United States National Institutes of Health, the project is being developed at the Altino Ventura Foundation, a Brazilian health nonprofit, in partnership with the U.S. research organization RTI International. Because the project is done in partnership with other organizations, Ventura says it's not solely up to her to provide this feedback.

"This criticism applies to our own institution and I try my best to push for these answers" from our research partners, says Ventura. "The mothers see that we're collecting data and they want to know: What about my kid?" she adds. "Is he getting better?"

Van der Linden wrote that when he invites a family to participate in a study, he tries to make it clear that the goal is to better understand the condition and that the findings might not benefit the participants themselves. "I explain that after the study is done, there won't be a 'result.' Sincerely, I don't offer or promise to call each one to explain the details, etc. I always make it clear that it is for science," he wrote to Undark by email. "I believe there might have been an over-expectation, or an unrealistic expectation of something that was never promised."

Soraya Fleischer, an anthropologist at the University of Braslia who coordinates a research project on the impact of Zika on the lives of families, says it's also important to consider what these mothers mean when they ask for study results. "For the researchers, the result is what is published in a well-qualified scientific journal or goes into their resume," she says. But for the families, says Fleischer, sometimes the result is a simple blood test that confirms that the child's disabilities were caused by Zika an important document that grants access to certain social benefits reserved for children with the syndrome, which can be difficult to get via the public health system.

Not every parent has had a bad experience with Zika researchers. Jaqueline Silva de Oliveira, the mother of a 5-year-old girl with congenital Zika syndrome, says that whenever she needs these types of reports in order to claim social benefits, she reaches out to the scientist who enrolled her family in a genetics study. The girl's twin brother was not affected by Zika, which caught the attention of a group at the Human Genome and Stem Cell Research Center at the University of So Paulo that wanted to try to identify potential protective genes.

"I participated to be able to help prevent other children from having microcephaly," says de Oliveira. She says she can't explain in her words what the results of the study were and she didn't receive a document describing them. But overall, she thinks having participated in the study was a positive experience. She continues to have a connection with the researchers, and they helped her find a neurologist, one of the best in the state, she says, who managed to control her daughter's epilepsy crises. "I helped the researcher on the study," she says, "and when I needed it, she helped me."

During the initial 2015 Zika outbreak and the years that followed, participation in the Brazilian Zika studies could be difficult. Luciana Lira, a medical anthropologist at the Federal University of Pernambuco, recalls accompanying two mothers to an event in 2018 in Recife, in Pernambuco state, one of the epicenters of the congenital Zika syndrome outbreak. The event was organized by a local university and an association for families of children with rare diseases. While the other mothers attended talks and participated in conversation circles, the mothers of children with congenital Zika syndrome were directed to a hall where researchers organized a task force to collect blood for a research project.

On that occasion, Lira says she watched while a nurse approached a mother to participate in the study. The mother "was so agitated that, when the nurse approached her and started explaining the study, she clearly wasn't paying full attention because there were more urgent things to deal with. Her daughter was having a crying fit, she had to fix her feeding tube, all of that," says Lira. "Then she agreed to participate, signed a paper and that's it. This type of situation has become very commonplace."

The researcher behind the project was Nilson Antonio de Assuno, a chemistry professor at the Federal University of So Paulo who was then studying the biochemical characteristics of blood among children with Zika. The study hasn't been published yet, de Assuno says, adding that he is aware that some families don't fully understand the purpose of his research when they agree to participate. "They get nervous because they are at an event, these are humble people, their children are crying and they end up not understanding very well what we're explaining."

De Assuno says there isn't much to be done about creating better strategies to communicate with families of children participating in studies. "I have been noticing this distrust in families," he says, "but those who end up losing are the families themselves." He says that he has previously tried to explain and educate the population about his work. "No matter what you do," he adds, "there will always be this distrust."

Lira and her colleagues have been observing the relationship between caregivers of children with Zika and biomedical scientists in Recife. Silvana Matos, also an anthropologist at the Federal University of Pernambuco, says that initially the caregivers welcomed the attention from scientists because they wanted to understand what had happened to their children. "The thing they complained the most about, right after this initial period," she says, "was that the test results never came back to them and the researchers, from Brazil or abroad, never reached out again to tell them what happened."

The families' experiences with the medical trials made them wary of researchers more broadly. By the time the anthropologists started working with the families in late 2016, they had to redesign their work to deal with this research fatigue and gain trust, says Lira. The families "had been overwhelmed both by scientists trying to collect organic samples, and by journalists and researchers wanting to interview them," says Fleischer. "There was an eagerness to learn what was happening" among the scientists and journalists, she adds, and the families "were the source."

Lira spent several months following caregivers around before doing any interviews. Fleischer, who is not based in Recife, decided to come back to the city several times over the years to revisit the families and show them what had been produced with the data they had collected before for example, an article or a newspaper story. Realizing that the caretakers were too busy to read long articles, Fleischer's group created a blog to publish short stories about life with Zika that they would print out and distribute to the participants during their visits. The fact that the researchers kept coming back and reporting what they were doing made the families feel respected, according to Fleischer, and it was essential to build trust.

Dos Santos, left, with her daughters. Dos Santos says she feels used and that many other families share the same sentiment. Medical anthropologist Luciana Lira says the families became overwhelmed by scientists and journalists, and that she had to change her approach to gain the families' trust. Ueslie Marcilino/Undark Magazine hide caption

Dos Santos, left, with her daughters. Dos Santos says she feels used and that many other families share the same sentiment. Medical anthropologist Luciana Lira says the families became overwhelmed by scientists and journalists, and that she had to change her approach to gain the families' trust.

In Brazil, the ethical and legal framework for research involving human subjects was established in 1996 through a resolution by the Brazilian National Council of Health. To conduct a study involving human subjects in Brazil, researchers have to submit their proposal to a research ethics committee, much like in the U.S. Every research organization may constitute its own committee, which responds to the National Commission for Research Ethics (CONEP, by its Portuguese acronym).

Before entering a study, participants must sign a free and informed consent form, a document that describes the study, its goals and possible risks and benefits of participating. According to the commission, the document should be written in clear and accessible language.

The need to share the findings with participants, which is at the core of the caregivers' complaints, is not directly covered by the 1996 resolution. But the current ethical norms, in force since 2012, do state that research findings should be communicated to the community if there's a potential to benefit the population, notes biologist Maria Mercedes Bendati, who retired from the municipal health department of Porto Alegre, in southern Brazil, in 2017 and is a CONEP member. "It already says that it is important to give this feedback," she says. The next step, she adds, is to implement the requirement "and make it very clear in the academic education of the researchers that they should fulfill their social role, and know that the research implies giving these answers to the participants."

Bendati participated in the Pan American Health Organization Zika Ethics Consultation in April 2016, which originated an ethics guidance on key issues raised by the Zika outbreak.

Florencia Luna, the chair of the Zika Ethics Consultation, says the goal of the guidance was precisely to prevent situations like the ones the caregivers described. "We were very concerned about doing this research at that moment in the middle of the outbreak. So it's a little bit like now, with COVID," she says. "Even if you want to do [research] fast and quick, and you should do it like that, that doesn't mean you have to avoid ethical standards."

Luna, who is also the director of the bioethics program at the Latin American Faculty of Social Sciences in Argentina, believes that returning to the participants with the results is an ethical obligation. "Personally, I do think it is very important to come back and tell the good or the bad news," she says, especially with Zika, which involves mothers and babies with health conditions. "At least to send them a letter, to call them on the phone," she adds. "Maybe not to make them go to the clinic because it would be too burdensome for them, but there are other ways where you can communicate nowadays, with smartphones, with the internet."

According to the International Ethical Guidelines for Health-related Research Involving Humans, a 2016 document prepared by the Council for International Organizations of Medical Sciences in collaboration with the World Health Organization, researchers "should engage potential participants and communities in a meaningful participatory process" which includes the dissemination of the study's results.

Despite such guidelines, not communicating results to participants is seen by some researchers as business as usual. Carl Elliott, an expert in bioethics and a professor of philosophy at the University of Minnesota, says the situation narrated by Rochelle dos Santos, where the investigator hesitated to send her the study for which her daughter had collaborated, didn't surprise him.

"If I were the research subject or the mother of the research subject, it would offend me and I think justifiably," he says. "That said, I think the vast majority of research subjects don't do that sort of follow-up. They don't ask or are not even particularly interested in the papers." Elliot says he doesn't think the investigator gave the right response, but he imagines he was probably surprised by the request.

In any case, Elliott says he believes that, if a participant actively asks, the researcher must provide the results: "It's shameful that it takes so much effort, and often money, for the public to get access to the results of scientific studies published in the medical literature."

Bioethics expert Carl Elliot says that the situation Rochelle dos Santos (pictured) described, where the investigator hesitated to send her the study for which her daughter had collaborated, didn't surprise him. Ueslie Marcilino/Undark Magazine hide caption

Bioethics expert Carl Elliot says that the situation Rochelle dos Santos (pictured) described, where the investigator hesitated to send her the study for which her daughter had collaborated, didn't surprise him.

In September 2018, the Brazilian caregivers' discontent culminated at the annual Congress of the Brazilian Society of Tropical Medicine in Recife. That year, the program included several sessions about congenital Zika syndrome. According to a paper written by Lira, none of the families' associations had been invited.

During one of the sessions on the main stage, Germana Soares, the mother of a boy with congenital Zika syndrome and the president of one of the largest family associations, requested to speak. She read aloud a letter to the event's organizers. "We believe there is a lack of empathy and sensitivity to our reality, and a lack of respect in the fact that we were underestimated. As if we the mothers, relatives and caretakers would lack the understanding to participate in a technical event to discuss a topic that is of our biggest interest," the letter stated. "Are we mothers so ignorant, without the least bit of education, that we cannot understand a scientific article or a lecture? Or should the researchers be the ones to use a language that is more comprehensible? Are we totally wrong to demand a discussion about ethics in biomedical research? Are we just numbers?"

The organizers were apparently caught by surprise, as Soares' speech wasn't in the program. One of the speakers at the session called Sinval Pinto Brando Filho, the president of the Society, to ask him what to do about it. He advised him to let Soares speak. "Our organization welcomes this debate with great satisfaction because we study the tropical diseases, in terms of controlling them," says Brando Filho, adding that every year the Brazilian Society of Tropical Medicine invites patients of neglected diseases to a public forum during the congress to discuss the problems they face. "I see this as something specific that was immediately recognized that it should be more sensitively incorporated into the tribute session."

Today, only sporadic cases of congenital Zika syndrome still occur, which makes it difficult to get funding for research, scientists say. The research focus has shifted to COVID-19, but the Zika health emergency might have left a legacy when it comes to research ethics.

"My personal reflection about the Zika experience in ethics committees is that perhaps there should have been a dialogue with the researchers to ask them how the findings would be shared with the participants," says Bendati. "When it comes to COVID-19, the CONEP is now being very clear on the need for a proposal of feedback to be given to participants." Learning from the mistakes of Zika might have contributed to this evolution, Bendati adds.

Luna says she's aware that sometimes ethics are viewed as an obstacle to science. Tracking down the participants can be difficult, and researchers who might have moved on to another project often lack the time and the energy to pursue it. "But it's part of what we have to do in order to build trust, to continue working," she says. "If not, these women will not collaborate in any other research in their lives because they were disappointed."

Mariana Lenharo is a science and health journalist whose writing has appeared in Scientific American, Mother Jones, Elemental, BBC News Brazil, among other publications. She is currently based in So Paulo, Brazil.

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To study Zika, they offered their kids. Then they were forgotten. : Goats and Soda - NPR

Genetics is the core of biology. Human genetics as a discipline is a central feature of modern biology and now of modern medicine as well. Human genetics and genomics, along with the related field of precision medicine, continue to generate both great excitement and genuine discovery. In current research practice, human genetics often forms the bridge between traditional wet-lab biological research and medicine. Post-graduate education in human genetics is an increasingly attractive route to the PhD due to the broad and interdisciplinary nature of this research and to the increasing capability of non-clinical researchers to contribute to medically relevant research. Graduate students recognize that the interdisciplinary nature of modern human genetics research prepares them for a rich and varied research career instead of funneling them into a very tight sub-specialty field. The translational nature of modern human genetics satisfies the need to contribute to health and medical care which we often see described as a major motivation for our graduate student to enter a PhD program. Recent events have only strengthened the urgency that young scientists feel to contribute to biomedical research in a meaningful way.

The Vanderbilt Human Genetics PhD program (HGEN) has served as a model of successful interdisciplinary biomedical research to graduate students since its inception. Modern human genetics research relies more and more on large scale biobanks combined with de-identified medical records, and HGEN has been intensively training graduate students in these research methods for over 10 years, far earlier than other institutions. We were able to start training graduate students in this new research area early due to the founding of our own large local biobank, BioVU, in 2008. That valuable research experience has allowed the students supported by this training grant to go forward into successful research careers as the increasing development of both regional and national biobank research efforts have increased, placing their educational experience in high demand.

There is a growing need nationally for scientists educated in computational biology, with genetics being one of the most quantitative and computational areas of modern biology. Vanderbilt University (VU) and Vanderbilt University Medical Center (VUMC) have invested hugely in human genetic and genomic science. With the establishment in 2015 of the Vanderbilt Genetics Institute (VGI), Vanderbilt has committed substantial new resources for establishing a research institute crossing both institutions, recruitment of additional faculty in genetics and genomics, and additional investment in genomic data for subjects in BioVU to facilitate further research by faculty and graduate students.

HGEN students have enjoyed unusual success in both productivity in graduate school (an average of 5.1 publications per student from graduate school research) and in being hired into academic human genetics programs (32% of HGEN alumni graduating >10 years ago now have faculty positions).

The goal of the Ph.D. Program in Human Genetics is to train students to explore scientific questions in genetics, with an emphasis on human disease. The program is designed to ensure technical proficiency in statistical and molecular techniques, provide current knowledge of genetics research and methods, and develop scientific communication skills. The program provides a cohesive experience that leverages the many facets of human genetics research at Vanderbilt, for the benefit of trainees and research mentors. Human Genetics is an equal opportunity graduate program and accepts qualified students regardless of cultural, social, demographic, or biological characteristics.

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Vanderbilt Human Genetics Program | Vanderbilt University

Grouping of humans based on shared physical or social qualities into categories

A race is a grouping of humans based on shared physical or social qualities into categories generally viewed as distinct within a given society.[1] The term was first used to refer to speakers of a common language and then to denote national affiliations. By the 17th century the term began to refer to physical (phenotypical) traits. Modern science regards race as a social construct, an identity which is assigned based on rules made by society.[2] While partially based on physical similarities within groups, race does not have an inherent physical or biological meaning.[1][3][4]

Social conceptions and groupings of races have varied over time, often involving folk taxonomies that define essential types of individuals based on perceived traits.[5] Today, scientists consider such biological essentialism obsolete, and generally discourage racial explanations for collective differentiation in both physical and behavioral traits.[7][8][9][10][11]

Even though there is a broad scientific agreement that essentialist and typological conceptions of race are untenable,[12][13][14][15][16][17] scientists around the world continue to conceptualize race in widely differing ways.[18] While some researchers continue to use the concept of race to make distinctions among fuzzy sets of traits or observable differences in behavior, others in the scientific community suggest that the idea of race is inherently naive[7] or simplistic.[19] Still others argue that, among humans, race has no taxonomic significance because all living humans belong to the same subspecies, Homo sapiens sapiens.[20][21]

Since the second half of the 20th century, the association of race with the discredited theories of scientific racism has contributed to race becoming increasingly seen as a largely pseudoscientific system of classification. Although still used in general contexts, race has often been replaced by less ambiguous and loaded terms: populations, people(s), ethnic groups, or communities, depending on context.[22][23]

Modern scholarship views racial categories as socially constructed, that is, race is not intrinsic to human beings but rather an identity created, often by socially dominant groups, to establish meaning in a social context. Different cultures define different racial groups, often focused on the largest groups of social relevance, and these definitions can change over time.

The establishment of racial boundaries often involves the subjugation of groups defined as racially inferior, as in the one-drop rule used in the 19th-century United States to exclude those with any amount of African ancestry from the dominant racial grouping, defined as "white".[1] Such racial identities reflect the cultural attitudes of imperial powers dominant during the age of European colonial expansion.[3] This view rejects the notion that race is biologically defined.[26][27][28][29]

According to geneticist David Reich, "while race may be a social construct, differences in genetic ancestry that happen to correlate to many of today's racial constructs are real."[30] In response to Reich, a group of 67 scientists from a broad range of disciplines wrote that his concept of race was "flawed" as "the meaning and significance of the groups is produced through social interventions".[31]

Although commonalities in physical traits such as facial features, skin color, and hair texture comprise part of the race concept, this linkage is a social distinction rather than an inherently biological one.[1] Other dimensions of racial groupings include shared history, traditions, and language. For instance, African-American English is a language spoken by many African Americans, especially in areas of the United States where racial segregation exists. Furthermore, people often self-identify as members of a race for political reasons.[1]

When people define and talk about a particular conception of race, they create a social reality through which social categorization is achieved.[32] In this sense, races are said to be social constructs.[33] These constructs develop within various legal, economic, and sociopolitical contexts, and may be the effect, rather than the cause, of major social situations.[clarify][34] While race is understood to be a social construct by many, most scholars agree that race has real material effects in the lives of people through institutionalized practices of preference and discrimination.

Socioeconomic factors, in combination with early but enduring views of race, have led to considerable suffering within disadvantaged racial groups.[35] Racial discrimination often coincides with racist mindsets, whereby the individuals and ideologies of one group come to perceive the members of an outgroup as both racially defined and morally inferior.[36] As a result, racial groups possessing relatively little power often find themselves excluded or oppressed, while hegemonic individuals and institutions are charged with holding racist attitudes.[37] Racism has led to many instances of tragedy, including slavery and genocide.[38]

In some countries, law enforcement uses race to profile suspects. This use of racial categories is frequently criticized for perpetuating an outmoded understanding of human biological variation, and promoting stereotypes. Because in some societies racial groupings correspond closely with patterns of social stratification, for social scientists studying social inequality, race can be a significant variable. As sociological factors, racial categories may in part reflect subjective attributions, self-identities, and social institutions.[39][40]

Scholars continue to debate the degrees to which racial categories are biologically warranted and socially constructed.[41] For example, in 2008, John Hartigan, Jr. argued for a view of race that focused primarily on culture, but which does not ignore the potential relevance of biology or genetics.[42] Accordingly, the racial paradigms employed in different disciplines vary in their emphasis on biological reduction as contrasted with societal construction.

In the social sciences, theoretical frameworks such as racial formation theory and critical race theory investigate implications of race as social construction by exploring how the images, ideas and assumptions of race are expressed in everyday life. A large body of scholarship has traced the relationships between the historical, social production of race in legal and criminal language, and their effects on the policing and disproportionate incarceration of certain groups.

Groups of humans have always identified themselves as distinct from neighboring groups, but such differences have not always been understood to be natural, immutable and global. These features are the distinguishing features of how the concept of race is used today. In this way the idea of race as we understand it today came about during the historical process of exploration and conquest which brought Europeans into contact with groups from different continents, and of the ideology of classification and typology found in the natural sciences.[43] The term race was often used in a general biological taxonomic sense,[22] starting from the 19th century, to denote genetically differentiated human populations defined by phenotype.[44][45]

The modern concept of race emerged as a product of the colonial enterprises of European powers from the 16th to 18th centuries which identified race in terms of skin color and physical differences. This way of classification would have been confusing for people in the ancient world since they did not categorize each other in such a fashion.[46] In particular, the epistemological moment where the modern concept of race was invented and rationalized lies somewhere between 1730 and 1790.[47]

According to Smedley and Marks the European concept of "race", along with many of the ideas now associated with the term, arose at the time of the scientific revolution, which introduced and privileged the study of natural kinds, and the age of European imperialism and colonization which established political relations between Europeans and peoples with distinct cultural and political traditions.[43][48] As Europeans encountered people from different parts of the world, they speculated about the physical, social, and cultural differences among various human groups. The rise of the Atlantic slave trade, which gradually displaced an earlier trade in slaves from throughout the world, created a further incentive to categorize human groups in order to justify the subordination of African slaves.[49]

Drawing on sources from classical antiquity and upon their own internal interactions for example, the hostility between the English and Irish powerfully influenced early European thinking about the differences between people[50] Europeans began to sort themselves and others into groups based on physical appearance, and to attribute to individuals belonging to these groups behaviors and capacities which were claimed to be deeply ingrained. A set of folk beliefs took hold that linked inherited physical differences between groups to inherited intellectual, behavioral, and moral qualities.[51] Similar ideas can be found in other cultures,[52] for example in China, where a concept often translated as "race" was associated with supposed common descent from the Yellow Emperor, and used to stress the unity of ethnic groups in China. Brutal conflicts between ethnic groups have existed throughout history and across the world.[53]

The first post-Graeco-Roman published classification of humans into distinct races seems to be Franois Bernier's Nouvelle division de la terre par les diffrents espces ou races qui l'habitent ("New division of Earth by the different species or races which inhabit it"), published in 1684.[54] In the 18th century the differences among human groups became a focus of scientific investigation. But the scientific classification of phenotypic variation was frequently coupled with racist ideas about innate predispositions of different groups, always attributing the most desirable features to the White, European race and arranging the other races along a continuum of progressively undesirable attributes. The 1735 classification of Carl Linnaeus, inventor of zoological taxonomy, divided the human species Homo sapiens into continental varieties of europaeus, asiaticus, americanus, and afer, each associated with a different humour: sanguine, melancholic, choleric, and phlegmatic, respectively.[55] Homo sapiens europaeus was described as active, acute, and adventurous, whereas Homo sapiens afer was said to be crafty, lazy, and careless.[57]

The 1775 treatise "The Natural Varieties of Mankind", by Johann Friedrich Blumenbach proposed five major divisions: the Caucasoid race, the Mongoloid race, the Ethiopian race (later termed Negroid), the American Indian race, and the Malayan race, but he did not propose any hierarchy among the races.[57] Blumenbach also noted the graded transition in appearances from one group to adjacent groups and suggested that "one variety of mankind does so sensibly pass into the other, that you cannot mark out the limits between them".[58]

From the 17th through 19th centuries, the merging of folk beliefs about group differences with scientific explanations of those differences produced what Smedley has called an "ideology of race".[48] According to this ideology, races are primordial, natural, enduring and distinct. It was further argued that some groups may be the result of mixture between formerly distinct populations, but that careful study could distinguish the ancestral races that had combined to produce admixed groups.[53] Subsequent influential classifications by Georges Buffon, Petrus Camper and Christoph Meiners all classified "Negros" as inferior to Europeans.[57] In the United States the racial theories of Thomas Jefferson were influential. He saw Africans as inferior to Whites especially in regards to their intellect, and imbued with unnatural sexual appetites, but described Native Americans as equals to whites.[59]

In the last two decades of the 18th century, the theory of polygenism, the belief that different races had evolved separately in each continent and shared no common ancestor,[60] was advocated in England by historian Edward Long and anatomist Charles White, in Germany by ethnographers Christoph Meiners and Georg Forster, and in France by Julien-Joseph Virey. In the US, Samuel George Morton, Josiah Nott and Louis Agassiz promoted this theory in the mid-19th century. Polygenism was popular and most widespread in the 19th century, culminating in the founding of the Anthropological Society of London (1863), which, during the period of the American Civil War, broke away from the Ethnological Society of London and its monogenic stance, their underlined difference lying, relevantly, in the so-called "Negro question": a substantial racist view by the former,[61] and a more liberal view on race by the latter.[62]

Today, all humans are classified as belonging to the species Homo sapiens. However, this is not the first species of homininae: the first species of genus Homo, Homo habilis, evolved in East Africa at least 2 million years ago, and members of this species populated different parts of Africa in a relatively short time. Homo erectus evolved more than 1.8 million years ago, and by 1.5 million years ago had spread throughout Europe and Asia. Virtually all physical anthropologists agree that Archaic Homo sapiens (A group including the possible species H. heidelbergensis, H. rhodesiensis and H. neanderthalensis) evolved out of African Homo erectus (sensu lato) or Homo ergaster.[63][64] Anthropologists support the idea that anatomically modern humans (Homo sapiens) evolved in North or East Africa from an archaic human species such as H. heidelbergensis and then migrated out of Africa, mixing with and replacing H. heidelbergensis and H. neanderthalensis populations throughout Europe and Asia, and H. rhodesiensis populations in Sub-Saharan Africa (a combination of the Out of Africa and Multiregional models).[65][verification needed]

In the early 20th century, many anthropologists taught that race was an entirely biological phenomenon and that this was core to a person's behavior and identity, a position commonly called racial essentialism.[66] This, coupled with a belief that linguistic, cultural, and social groups fundamentally existed along racial lines, formed the basis of what is now called scientific racism.[67] After the Nazi eugenics program, along with the rise of anti-colonial movements, racial essentialism lost widespread popularity.[68] New studies of culture and the fledgling field of population genetics undermined the scientific standing of racial essentialism, leading race anthropologists to revise their conclusions about the sources of phenotypic variation.[66] A significant number of modern anthropologists and biologists in the West came to view race as an invalid genetic or biological designation.[69]

The first to challenge the concept of race on empirical grounds were the anthropologists Franz Boas, who provided evidence of phenotypic plasticity due to environmental factors,[70] and Ashley Montagu, who relied on evidence from genetics.[71] E. O. Wilson then challenged the concept from the perspective of general animal systematics, and further rejected the claim that "races" were equivalent to "subspecies".[72]

Human genetic variation is predominantly within races, continuous, and complex in structure, which is inconsistent with the concept of genetic human races.[73] According to the biological anthropologist Jonathan Marks,[43]

By the 1970s, it had become clear that (1) most human differences were cultural; (2) what was not cultural was principally polymorphic that is to say, found in diverse groups of people at different frequencies; (3) what was not cultural or polymorphic was principally clinal that is to say, gradually variable over geography; and (4) what was left the component of human diversity that was not cultural, polymorphic, or clinal was very small.

A consensus consequently developed among anthropologists and geneticists that race as the previous generation had known it as largely discrete, geographically distinct, gene pools did not exist.

The term race in biology is used with caution because it can be ambiguous. Generally, when it is used it is effectively a synonym of subspecies.[74] (For animals, the only taxonomic unit below the species level is usually the subspecies;[75] there are narrower infraspecific ranks in botany, and race does not correspond directly with any of them.) Traditionally, subspecies are seen as geographically isolated and genetically differentiated populations.[76] Studies of human genetic variation show that human populations are not geographically isolated,[77] and their genetic differences are far smaller than those among comparable subspecies.[78]

In 1978, Sewall Wright suggested that human populations that have long inhabited separated parts of the world should, in general, be considered different subspecies by the criterion that most individuals of such populations can be allocated correctly by inspection. Wright argued that, "It does not require a trained anthropologist to classify an array of Englishmen, West Africans, and Chinese with 100% accuracy by features, skin color, and type of hair despite so much variability within each of these groups that every individual can easily be distinguished from every other."[79] While in practice subspecies are often defined by easily observable physical appearance, there is not necessarily any evolutionary significance to these observed differences, so this form of classification has become less acceptable to evolutionary biologists.[80] Likewise this typological approach to race is generally regarded as discredited by biologists and anthropologists.[81][14]

In 2000, philosopher Robin Andreasen proposed that cladistics might be used to categorize human races biologically, and that races can be both biologically real and socially constructed.[82] Andreasen cited tree diagrams of relative genetic distances among populations published by Luigi Cavalli-Sforza as the basis for a phylogenetic tree of human races (p.661). Biological anthropologist Jonathan Marks (2008) responded by arguing that Andreasen had misinterpreted the genetic literature: "These trees are phenetic (based on similarity), rather than cladistic (based on monophyletic descent, that is from a series of unique ancestors)."[83] Evolutionary biologist Alan Templeton (2013) argued that multiple lines of evidence falsify the idea of a phylogenetic tree structure to human genetic diversity, and confirm the presence of gene flow among populations.[29] Marks, Templeton, and Cavalli-Sforza all conclude that genetics does not provide evidence of human races.[29][84]

Previously, anthropologists Lieberman and Jackson (1995) had also critiqued the use of cladistics to support concepts of race. They argued that "the molecular and biochemical proponents of this model explicitly use racial categories in their initial grouping of samples". For example, the large and highly diverse macroethnic groups of East Indians, North Africans, and Europeans are presumptively grouped as Caucasians prior to the analysis of their DNA variation. They argued that this a priori grouping limits and skews interpretations, obscures other lineage relationships, deemphasizes the impact of more immediate clinal environmental factors on genomic diversity, and can cloud our understanding of the true patterns of affinity.[85]

In 2015, Keith Hunley, Graciela Cabana, and Jeffrey Long analyzed the Human Genome Diversity Project sample of 1,037 individuals in 52 populations,[86] finding that non-African populations are a taxonomic subgroup of African populations, that "some African populations are equally related to other African populations and to non-African populations," and that "outside of Africa, regional groupings of populations are nested inside one another, and many of them are not monophyletic."[86] Earlier research had also suggested that there has always been considerable gene flow between human populations, meaning that human population groups are not monophyletic.[76] Rachel Caspari has argued that, since no groups currently regarded as races are monophyletic, by definition none of these groups can be clades.

One crucial innovation in reconceptualizing genotypic and phenotypic variation was the anthropologist C. Loring Brace's observation that such variations, insofar as it is affected by natural selection, slow migration, or genetic drift, are distributed along geographic gradations or clines.[88] For example, with respect to skin color in Europe and Africa, Brace writes:

To this day, skin color grades by imperceptible means from Europe southward around the eastern end of the Mediterranean and up the Nile into Africa. From one end of this range to the other, there is no hint of a skin color boundary, and yet the spectrum runs from the lightest in the world at the northern edge to as dark as it is possible for humans to be at the equator.

In part this is due to isolation by distance. This point called attention to a problem common to phenotype-based descriptions of races (for example, those based on hair texture and skin color): they ignore a host of other similarities and differences (for example, blood type) that do not correlate highly with the markers for race. Thus, anthropologist Frank Livingstone's conclusion, that since clines cross racial boundaries, "there are no races, only clines".[90]

In a response to Livingstone, Theodore Dobzhansky argued that when talking about race one must be attentive to how the term is being used: "I agree with Dr. Livingstone that if races have to be 'discrete units', then there are no races, and if 'race' is used as an 'explanation' of the human variability, rather than vice versa, then the explanation is invalid." He further argued that one could use the term race if one distinguished between "race differences" and "the race concept". The former refers to any distinction in gene frequencies between populations; the latter is "a matter of judgment". He further observed that even when there is clinal variation, "Race differences are objectively ascertainable biological phenomena... but it does not follow that racially distinct populations must be given racial (or subspecific) labels."[90] In short, Livingstone and Dobzhansky agree that there are genetic differences among human beings; they also agree that the use of the race concept to classify people, and how the race concept is used, is a matter of social convention. They differ on whether the race concept remains a meaningful and useful social convention.

Skin color (above) and blood type B (below) are nonconcordant traits since their geographical distribution is not similar.

In 1964, the biologists Paul Ehrlich and Holm pointed out cases where two or more clines are distributed discordantly for example, melanin is distributed in a decreasing pattern from the equator north and south; frequencies for the haplotype for beta-S hemoglobin, on the other hand, radiate out of specific geographical points in Africa.[91] As the anthropologists Leonard Lieberman and Fatimah Linda Jackson observed, "Discordant patterns of heterogeneity falsify any description of a population as if it were genotypically or even phenotypically homogeneous".[85]

Patterns such as those seen in human physical and genetic variation as described above, have led to the consequence that the number and geographic location of any described races is highly dependent on the importance attributed to, and quantity of, the traits considered. Scientists discovered a skin-lighting mutation that partially accounts for the appearance of Light skin in humans (people who migrated out of Africa northward into what is now Europe) which they estimate occurred 20,000 to 50,000 years ago. The East Asians owe their relatively light skin to different mutations.[92] On the other hand, the greater the number of traits (or alleles) considered, the more subdivisions of humanity are detected, since traits and gene frequencies do not always correspond to the same geographical location. Or as Ossorio & Duster (2005) put it:

Anthropologists long ago discovered that humans' physical traits vary gradually, with groups that are close geographic neighbors being more similar than groups that are geographically separated. This pattern of variation, known as clinal variation, is also observed for many alleles that vary from one human group to another. Another observation is that traits or alleles that vary from one group to another do not vary at the same rate. This pattern is referred to as nonconcordant variation. Because the variation of physical traits is clinal and nonconcordant, anthropologists of the late 19th and early 20th centuries discovered that the more traits and the more human groups they measured, the fewer discrete differences they observed among races and the more categories they had to create to classify human beings. The number of races observed expanded to the 1930s and 1950s, and eventually anthropologists concluded that there were no discrete races.[93] Twentieth and 21st century biomedical researchers have discovered this same feature when evaluating human variation at the level of alleles and allele frequencies. Nature has not created four or five distinct, nonoverlapping genetic groups of people.

Another way to look at differences between populations is to measure genetic differences rather than physical differences between groups. The mid-20th-century anthropologist William C. Boyd defined race as: "A population which differs significantly from other populations in regard to the frequency of one or more of the genes it possesses. It is an arbitrary matter which, and how many, gene loci we choose to consider as a significant 'constellation'".[94] Leonard Lieberman and Rodney Kirk have pointed out that "the paramount weakness of this statement is that if one gene can distinguish races then the number of races is as numerous as the number of human couples reproducing."[95] Moreover, the anthropologist Stephen Molnar has suggested that the discordance of clines inevitably results in a multiplication of races that renders the concept itself useless.[96] The Human Genome Project states "People who have lived in the same geographic region for many generations may have some alleles in common, but no allele will be found in all members of one population and in no members of any other."[97] Massimo Pigliucci and Jonathan Kaplan argue that human races do exist, and that they correspond to the genetic classification of ecotypes, but that real human races do not correspond very much, if at all, to folk racial categories.[98] In contrast, Walsh & Yun reviewed the literature in 2011 and reported that "Genetic studies using very few chromosomal loci find that genetic polymorphisms divide human populations into clusters with almost 100 percent accuracy and that they correspond to the traditional anthropological categories."[99]

Some biologists argue that racial categories correlate with biological traits (e.g. phenotype), and that certain genetic markers have varying frequencies among human populations, some of which correspond more or less to traditional racial groupings.

The distribution of genetic variants within and among human populations are impossible to describe succinctly because of the difficulty of defining a population, the clinal nature of variation, and heterogeneity across the genome (Long and Kittles 2003). In general, however, an average of 85% of statistical genetic variation exists within local populations, ~7% is between local populations within the same continent, and ~8% of variation occurs between large groups living on different continents.[102] The recent African origin theory for humans would predict that in Africa there exists a great deal more diversity than elsewhere and that diversity should decrease the further from Africa a population is sampled. Hence, the 85% average figure is misleading: Long and Kittles find that rather than 85% of human genetic diversity existing in all human populations, about 100% of human diversity exists in a single African population, whereas only about 60% of human genetic diversity exists in the least diverse population they analyzed (the Surui, a population derived from New Guinea).[103] Statistical analysis that takes this difference into account confirms previous findings that, "Western-based racial classifications have no taxonomic significance."[86]

A 2002 study of random biallelic genetic loci found little to no evidence that humans were divided into distinct biological groups.[104]

In his 2003 paper, "Human Genetic Diversity: Lewontin's Fallacy", A. W. F. Edwards argued that rather than using a locus-by-locus analysis of variation to derive taxonomy, it is possible to construct a human classification system based on characteristic genetic patterns, or clusters inferred from multilocus genetic data.[105][106] Geographically based human studies since have shown that such genetic clusters can be derived from analyzing of a large number of loci which can assort individuals sampled into groups analogous to traditional continental racial groups.[107] Joanna Mountain and Neil Risch cautioned that while genetic clusters may one day be shown to correspond to phenotypic variations between groups, such assumptions were premature as the relationship between genes and complex traits remains poorly understood.[109] However, Risch denied such limitations render the analysis useless: "Perhaps just using someone's actual birth year is not a very good way of measuring age. Does that mean we should throw it out? ... Any category you come up with is going to be imperfect, but that doesn't preclude you from using it or the fact that it has utility."[110]

Early human genetic cluster analysis studies were conducted with samples taken from ancestral population groups living at extreme geographic distances from each other. It was thought that such large geographic distances would maximize the genetic variation between the groups sampled in the analysis, and thus maximize the probability of finding cluster patterns unique to each group. In light of the historically recent acceleration of human migration (and correspondingly, human gene flow) on a global scale, further studies were conducted to judge the degree to which genetic cluster analysis can pattern ancestrally identified groups as well as geographically separated groups. One such study looked at a large multiethnic population in the United States, and "detected only modest genetic differentiation between different current geographic locales within each race/ethnicity group. Thus, ancient geographic ancestry, which is highly correlated with self-identified race/ethnicity as opposed to current residence is the major determinant of genetic structure in the U.S. population."

Witherspoon et al. (2007) have argued that even when individuals can be reliably assigned to specific population groups, it may still be possible for two randomly chosen individuals from different populations/clusters to be more similar to each other than to a randomly chosen member of their own cluster. They found that many thousands of genetic markers had to be used in order for the answer to the question "How often is a pair of individuals from one population genetically more dissimilar than two individuals chosen from two different populations?" to be "never". This assumed three population groups separated by large geographic ranges (European, African and East Asian). The entire world population is much more complex and studying an increasing number of groups would require an increasing number of markers for the same answer. The authors conclude that "caution should be used when using geographic or genetic ancestry to make inferences about individual phenotypes."[111] Witherspoon, et al. concluded that, "The fact that, given enough genetic data, individuals can be correctly assigned to their populations of origin is compatible with the observation that most human genetic variation is found within populations, not between them. It is also compatible with our nding that, even when the most distinct populations are considered and hundreds of loci are used, individuals are frequently more similar to members of other populations than to members of their own population."[111]

Anthropologists such as C. Loring Brace,[112] the philosophers Jonathan Kaplan and Rasmus Winther,[113][114][115] and the geneticist Joseph Graves,[19] have argued that while there it is certainly possible to find biological and genetic variation that corresponds roughly to the groupings normally defined as "continental races", this is true for almost all geographically distinct populations. The cluster structure of the genetic data is therefore dependent on the initial hypotheses of the researcher and the populations sampled. When one samples continental groups, the clusters become continental; if one had chosen other sampling patterns, the clustering would be different. Weiss and Fullerton have noted that if one sampled only Icelanders, Mayans and Maoris, three distinct clusters would form and all other populations could be described as being clinally composed of admixtures of Maori, Icelandic and Mayan genetic materials.[117] Kaplan and Winther therefore argue that, seen in this way, both Lewontin and Edwards are right in their arguments. They conclude that while racial groups are characterized by different allele frequencies, this does not mean that racial classification is a natural taxonomy of the human species, because multiple other genetic patterns can be found in human populations that crosscut racial distinctions. Moreover, the genomic data underdetermines whether one wishes to see subdivisions (i.e., splitters) or a continuum (i.e., lumpers). Under Kaplan and Winther's view, racial groupings are objective social constructions (see Mills 1998[118]) that have conventional biological reality only insofar as the categories are chosen and constructed for pragmatic scientific reasons. In earlier work, Winther had identified "diversity partitioning" and "clustering analysis" as two separate methodologies, with distinct questions, assumptions, and protocols. Each is also associated with opposing ontological| consequences vis-a-vis the metaphysics of race.[119] Philosopher Lisa Gannett has argued that biogeographical ancestry, a concept devised by Mark Shriver and Tony Frudakis, is not an objective measure of the biological aspects of race as Shriver and Frudakis claim it is. She argues that it is actually just a "local category shaped by the U.S. context of its production, especially the forensic aim of being able to predict the race or ethnicity of an unknown suspect based on DNA found at the crime scene."[120]

Recent studies of human genetic clustering have included a debate over how genetic variation is organized, with clusters and clines as the main possible orderings. Serre & Pbo (2004) argued for smooth, clinal genetic variation in ancestral populations even in regions previously considered racially homogeneous, with the apparent gaps turning out to be artifacts of sampling techniques. Rosenberg et al. (2005) disputed this and offered an analysis of the Human Genetic Diversity Panel showing that there were small discontinuities in the smooth genetic variation for ancestral populations at the location of geographic barriers such as the Sahara, the Oceans, and the Himalayas. Nonetheless, Rosenberg et al. (2005) stated that their findings "should not be taken as evidence of our support of any particular concept of biological race... Genetic differences among human populations derive mainly from gradations in allele frequencies rather than from distinctive 'diagnostic' genotypes." Using a sample of 40 populations distributed roughly evenly across the Earth's land surface, Xing & et. al. (2010, p.208) found that "genetic diversity is distributed in a more clinal pattern when more geographically intermediate populations are sampled."

Guido Barbujani has written that human genetic variation is generally distributed continuously in gradients across much of Earth, and that there is no evidence that genetic boundaries between human populations exist as would be necessary for human races to exist.[121]

Over time, human genetic variation has formed a nested structure that is inconsistent with the concept of races that have evolved independently of one another.[122]

As anthropologists and other evolutionary scientists have shifted away from the language of race to the term population to talk about genetic differences, historians, cultural anthropologists and other social scientists re-conceptualized the term "race" as a cultural category or social construct, i.e., a way among many possible ways in which a society chooses to divide its members into categories.

Many social scientists have replaced the word race with the word "ethnicity" to refer to self-identifying groups based on beliefs concerning shared culture, ancestry and history. Alongside empirical and conceptual problems with "race", following the Second World War, evolutionary and social scientists were acutely aware of how beliefs about race had been used to justify discrimination, apartheid, slavery, and genocide. This questioning gained momentum in the 1960s during the civil rights movement in the United States and the emergence of numerous anti-colonial movements worldwide. They thus came to believe that race itself is a social construct, a concept that was believed to correspond to an objective reality but which was believed in because of its social functions.[123]

Craig Venter and Francis Collins of the National Institute of Health jointly made the announcement of the mapping of the human genome in 2000. Upon examining the data from the genome mapping, Venter realized that although the genetic variation within the human species is on the order of 13% (instead of the previously assumed 1%), the types of variations do not support notion of genetically defined races. Venter said, "Race is a social concept. It's not a scientific one. There are no bright lines (that would stand out), if we could compare all the sequenced genomes of everyone on the planet." "When we try to apply science to try to sort out these social differences, it all falls apart."[124]

Anthropologist Stephan Palmi has argued that race "is not a thing but a social relation"; or, in the words of Katya Gibel Mevorach, "a metonym", "a human invention whose criteria for differentiation are neither universal nor fixed but have always been used to manage difference." As such, the use of the term "race" itself must be analyzed. Moreover, they argue that biology will not explain why or how people use the idea of race; only history and social relationships will.

Imani Perry has argued that race "is produced by social arrangements and political decision making",[127] and that "race is something that happens, rather than something that is. It is dynamic, but it holds no objective truth."[128] Similarly, Racial Culture: A Critique (2005), Richard T. Ford argued that while "there is no necessary correspondence between the ascribed identity of race and one's culture or personal sense of self" and "group difference is not intrinsic to members of social groups but rather contingent o[n] the social practices of group identification", the social practices of identity politics may coerce individuals into the "compulsory" enactment of "prewritten racial scripts".[129]

Compared to 19th-century United States, 20th-century Brazil was characterized by a perceived relative absence of sharply defined racial groups. According to anthropologist Marvin Harris, this pattern reflects a different history and different social relations.

Race in Brazil was "biologized", but in a way that recognized the difference between ancestry (which determines genotype) and phenotypic differences. There, racial identity was not governed by rigid descent rule, such as the one-drop rule, as it was in the United States. A Brazilian child was never automatically identified with the racial type of one or both parents, nor were there only a very limited number of categories to choose from,[130] to the extent that full siblings can pertain to different racial groups.[131]

Over a dozen racial categories would be recognized in conformity with all the possible combinations of hair color, hair texture, eye color, and skin color. These types grade into each other like the colors of the spectrum, and not one category stands significantly isolated from the rest. That is, race referred preferentially to appearance, not heredity, and appearance is a poor indication of ancestry, because only a few genes are responsible for someone's skin color and traits: a person who is considered white may have more African ancestry than a person who is considered black, and the reverse can be also true about European ancestry.[133] The complexity of racial classifications in Brazil reflects the extent of genetic mixing in Brazilian society, a society that remains highly, but not strictly, stratified along color lines. These socioeconomic factors are also significant to the limits of racial lines, because a minority of pardos, or brown people, are likely to start declaring themselves white or black if socially upward,[134] and being seen as relatively "whiter" as their perceived social status increases (much as in other regions of Latin America).[135]

Fluidity of racial categories aside, the "biologification" of race in Brazil referred above would match contemporary concepts of race in the United States quite closely, though, if Brazilians are supposed to choose their race as one among, Asian and Indigenous apart, three IBGE's census categories. While assimilated Amerindians and people with very high quantities of Amerindian ancestry are usually grouped as caboclos, a subgroup of pardos which roughly translates as both mestizo and hillbilly, for those of lower quantity of Amerindian descent a higher European genetic contribution is expected to be grouped as a pardo. In several genetic tests, people with less than 60-65% of European descent and 510% of Amerindian descent usually cluster with Afro-Brazilians (as reported by the individuals), or 6.9% of the population, and those with about 45% or more of Subsaharan contribution most times do so (in average, Afro-Brazilian DNA was reported to be about 50% Subsaharan African, 37% European and 13% Amerindian).[136][137][138][139]

If a more consistent report with the genetic groups in the gradation of genetic mixing is to be considered (e.g. that would not cluster people with a balanced degree of African and non-African ancestry in the black group instead of the multiracial one, unlike elsewhere in Latin America where people of high quantity of African descent tend to classify themselves as mixed), more people would report themselves as white and pardo in Brazil (47.7% and 42.4% of the population as of 2010, respectively), because by research its population is believed to have between 65 and 80% of autosomal European ancestry, in average (also >35% of European mt-DNA and >95% of European Y-DNA).[136][142][143][144]

From the last decades of the Empire until the 1950s, the proportion of the white population increased significantly while Brazil welcomed 5.5 million immigrants between 1821 and 1932, not much behind its neighbor Argentina with 6.4 million,[145] and it received more European immigrants in its colonial history than the United States. Between 1500 and 1760, 700.000 Europeans settled in Brazil, while 530.000 Europeans settled in the United States for the same given time.[146] Thus, the historical construction of race in Brazilian society dealt primarily with gradations between persons of majority European ancestry and little minority groups with otherwise lower quantity therefrom in recent times.

According to the Council of the European Union:

The European Union rejects theories which attempt to determine the existence of separate human races.

The European Union uses the terms racial origin and ethnic origin synonymously in its documents and according to it "the use of the term 'racial origin' in this directive does not imply an acceptance of such [racial] theories".[147][148][full citation needed] Haney Lpez[who?] warns that using "race" as a category within the law tends to legitimize its existence in the popular imagination. In the diverse geographic context of Europe, ethnicity and ethnic origin are arguably more resonant and are less encumbered by the ideological baggage associated with "race". In European context, historical resonance of "race" underscores its problematic nature. In some states, it is strongly associated with laws promulgated by the Nazi and Fascist governments in Europe during the 1930s and 1940s. Indeed, in 1996, the European Parliament adopted a resolution stating that "the term should therefore be avoided in all official texts".[149]

The concept of racial origin relies on the notion that human beings can be separated into biologically distinct "races", an idea generally rejected by the scientific community. Since all human beings belong to the same species, the ECRI (European Commission against Racism and Intolerance) rejects theories based on the existence of different "races". However, in its Recommendation ECRI uses this term in order to ensure that those persons who are generally and erroneously perceived as belonging to "another race" are not excluded from the protection provided for by the legislation. The law claims to reject the existence of "race", yet penalize situations where someone is treated less favourably on this ground.[149]

The immigrants to the United States came from every region of Europe, Africa, and Asia. They mixed among themselves and with the indigenous inhabitants of the continent. In the United States most people who self-identify as African American have some European ancestors, while many people who identify as European American have some African or Amerindian ancestors.

Since the early history of the United States, Amerindians, African Americans, and European Americans have been classified as belonging to different races. Efforts to track mixing between groups led to a proliferation of categories, such as mulatto and octoroon. The criteria for membership in these races diverged in the late 19th century. During Reconstruction, increasing numbers of Americans began to consider anyone with "one drop" of known "Black blood" to be Black, regardless of appearance. By the early 20th century, this notion was made statutory in many states. Amerindians continue to be defined by a certain percentage of "Indian blood" (called blood quantum). To be White one had to have perceived "pure" White ancestry. The one-drop rule or hypodescent rule refers to the convention of defining a person as racially black if he or she has any known African ancestry. This rule meant that those that were mixed race but with some discernible African ancestry were defined as black. The one-drop rule is specific to not only those with African ancestry but to the United States, making it a particularly African-American experience.[150]

The decennial censuses conducted since 1790 in the United States created an incentive to establish racial categories and fit people into these categories.[151]

The term "Hispanic" as an ethnonym emerged in the 20th century with the rise of migration of laborers from the Spanish-speaking countries of Latin America to the United States. Today, the word "Latino" is often used as a synonym for "Hispanic". The definitions of both terms are non-race specific, and include people who consider themselves to be of distinct races (Black, White, Amerindian, Asian, and mixed groups).[152] However, there is a common misconception in the US that Hispanic/Latino is a race[153] or sometimes even that national origins such as Mexican, Cuban, Colombian, Salvadoran, etc. are races. In contrast to "Latino" or "Hispanic", "Anglo" refers to non-Hispanic White Americans or non-Hispanic European Americans, most of whom speak the English language but are not necessarily of English descent.

The concept of race classification in physical anthropology lost credibility around the 1960s and is now considered untenable.[154] A 2019 statement by the American Association of Physical Anthropologists declares:

Race does not provide an accurate representation of human biological variation. It was never accurate in the past, and it remains inaccurate when referencing contemporary human populations. Humans are not divided biologically into distinct continental types or racial genetic clusters. Instead, the Western concept of race must be understood as a classification system that emerged from, and in support of, European colonialism, oppression, and discrimination.[81]

Wagner et al. (2017) surveyed 3,286 American anthropologists' views on race and genetics, including both cultural and biological anthropologists. They found a consensus among them that biological races do not exist in humans, but that race does exist insofar as the social experiences of members of different races can have significant effects on health.[155]

Wang, trkalj et al. (2003) examined the use of race as a biological concept in research papers published in China's only biological anthropology journal, Acta Anthropologica Sinica. The study showed that the race concept was widely used among Chinese anthropologists.[156][157] In a 2007 review paper, trkalj suggested that the stark contrast of the racial approach between the United States and China was due to the fact that race is a factor for social cohesion among the ethnically diverse people of China, whereas "race" is a very sensitive issue in America and the racial approach is considered to undermine social cohesion with the result that in the socio-political context of US academics scientists are encouraged not to use racial categories, whereas in China they are encouraged to use them.[158]

Lieberman et al. in a 2004 study researched the acceptance of race as a concept among anthropologists in the United States, Canada, the Spanish speaking areas, Europe, Russia and China. Rejection of race ranged from high to low, with the highest rejection rate in the United States and Canada, a moderate rejection rate in Europe, and the lowest rejection rate in Russia and China. Methods used in the studies reported included questionnaires and content analysis.[18]

Kaszycka et al. (2009) in 20022003 surveyed European anthropologists' opinions toward the biological race concept. Three factors, country of academic education, discipline, and age, were found to be significant in differentiating the replies. Those educated in Western Europe, physical anthropologists, and middle-aged persons rejected race more frequently than those educated in Eastern Europe, people in other branches of science, and those from both younger and older generations." The survey shows that the views on race are sociopolitically (ideologically) influenced and highly dependent on education."[159]

Since the second half of the 20th century, physical anthropology in the United States has moved away from a typological understanding of human biological diversity towards a genomic and population-based perspective. Anthropologists have tended to understand race as a social classification of humans based on phenotype and ancestry as well as cultural factors, as the concept is understood in the social sciences. Since 1932, an increasing number of college textbooks introducing physical anthropology have rejected race as a valid concept: from 1932 to 1976, only seven out of thirty-two rejected race; from 1975 to 1984, thirteen out of thirty-three rejected race; from 1985 to 1993, thirteen out of nineteen rejected race. According to one academic journal entry, where 78 percent of the articles in the 1931 Journal of Physical Anthropology employed these or nearly synonymous terms reflecting a bio-race paradigm, only 36 percent did so in 1965, and just 28 percent did in 1996.[161]

A 1998 "Statement on 'Race'" composed by a select committee of anthropologists and issued by the executive board of the American Anthropological Association, which they argue "represents generally the contemporary thinking and scholarly positions of a majority of anthropologists", declares:[162]

In the United States both scholars and the general public have been conditioned to viewing human races as natural and separate divisions within the human species based on visible physical differences. With the vast expansion of scientific knowledge in this century, however, it has become clear that human populations are not unambiguous, clearly demarcated, biologically distinct groups. Evidence from the analysis of genetics (e.g., DNA) indicates that most physical variation, about 94%, lies within so-called racial groups. Conventional geographic "racial" groupings differ from one another only in about 6% of their genes. This means that there is greater variation within "racial" groups than between them. In neighboring populations there is much overlapping of genes and their phenotypic (physical) expressions. Throughout history whenever different groups have come into contact, they have interbred. The continued sharing of genetic materials has maintained all of humankind as a single species. [...]With the vast expansion of scientific knowledge in this century, ... it has become clear that human populations are not unambiguous, clearly demarcated, biologically distinct groups. [...] Given what we know about the capacity of normal humans to achieve and function within any culture, we conclude that present-day inequalities between so-called "racial" groups are not consequences of their biological inheritance but products of historical and contemporary social, economic, educational, and political circumstances.

An earlier survey, conducted in 1985 (Lieberman et al. 1992), asked 1,200 American scientists how many disagree with the following proposition: "There are biological races in the species Homo sapiens." Among anthropologists, the responses were:

Lieberman's study also showed that more women reject the concept of race than men.[164]

The same survey, conducted again in 1999,[165] showed that the number of anthropologists disagreeing with the idea of biological race had risen substantially. The results were as follows:

A line of research conducted by Cartmill (1998), however, seemed to limit the scope of Lieberman's finding that there was "a significant degree of change in the status of the race concept". Goran trkalj has argued that this may be because Lieberman and collaborators had looked at all the members of the American Anthropological Association irrespective of their field of research interest, while Cartmill had looked specifically at biological anthropologists interested in human variation.[166]

In 2007, Ann Morning interviewed over 40 American biologists and anthropologists and found significant disagreements over the nature of race, with no one viewpoint holding a majority among either group. Morning also argues that a third position, "antiessentialism", which holds that race is not a useful concept for biologists, should be introduced into this debate in addition to "constructionism" and "essentialism".[167]

According to the 2000 University of Wyoming edition of a popular physical anthropology textbook, forensic anthropologists are overwhelmingly in support of the idea of the basic biological reality of human races. Forensic physical anthropologist and professor George W. Gill has said that the idea that race is only skin deep "is simply not true, as any experienced forensic anthropologist will affirm" and "Many morphological features tend to follow geographic boundaries coinciding often with climatic zones. This is not surprising since the selective forces of climate are probably the primary forces of nature that have shaped human races with regard not only to skin color and hair form but also the underlying bony structures of the nose, cheekbones, etc. (For example, more prominent noses humidify air better.)" While he can see good arguments for both sides, the complete denial of the opposing evidence "seems to stem largely from socio-political motivation and not science at all". He also states that many biological anthropologists see races as real yet "not one introductory textbook of physical anthropology even presents that perspective as a possibility. In a case as flagrant as this, we are not dealing with science but rather with blatant, politically motivated censorship".

In partial response to Gill's statement, Professor of Biological Anthropology C. Loring Brace argues that the reason laymen and biological anthropologists can determine the geographic ancestry of an individual can be explained by the fact that biological characteristics are clinally distributed across the planet, and that does not translate into the concept of race. He states:

Well, you may ask, why can't we call those regional patterns "races"? In fact, we can and do, but it does not make them coherent biological entities. "Races" defined in such a way are products of our perceptions. ... We realize that in the extremes of our transit Moscow to Nairobi, perhaps there is a major but gradual change in skin color from what we euphemistically call white to black, and that this is related to the latitudinal difference in the intensity of the ultraviolet component of sunlight. What we do not see, however, is the myriad other traits that are distributed in a fashion quite unrelated to the intensity of ultraviolet radiation. Where skin color is concerned, all the northern populations of the Old World are lighter than the long-term inhabitants near the equator. Although Europeans and Chinese are obviously different, in skin color they are closer to each other than either is to equatorial Africans. But if we test the distribution of the widely known ABO blood-group system, then Europeans and Africans are closer to each other than either is to Chinese.

The concept of "race" is still sometimes used within forensic anthropology (when analyzing skeletal remains), biomedical research, and race-based medicine.[170][171] Brace has criticized forensic anthropologists for this, arguing that they in fact should be talking about regional ancestry. He argues that while forensic anthropologists can determine that a skeletal remain comes from a person with ancestors in a specific region of Africa, categorizing that skeletal as being "black" is a socially constructed category that is only meaningful in the particular social context of the United States, and which is not itself scientifically valid.[172]

In the same 1985 survey (Lieberman et al. 1992), 16% of the surveyed biologists and 36% of the surveyed developmental psychologists disagreed with the proposition: "There are biological races in the species Homo sapiens."

The authors of the study also examined 77 college textbooks in biology and 69 in physical anthropology published between 1932 and 1989. Physical anthropology texts argued that biological races exist until the 1970s, when they began to argue that races do not exist. In contrast, biology textbooks did not undergo such a reversal but many instead dropped their discussion of race altogether. The authors attributed this to biologists trying to avoid discussing the political implications of racial classifications, and to the ongoing discussions in biology about the validity of the idea of "subspecies". The authors concluded, "The concept of race, masking the overwhelming genetic similarity of all peoples and the mosaic patterns of variation that do not correspond to racial divisions, is not only socially dysfunctional but is biologically indefensible as well (pp. 5 185 19)."(Lieberman et al. 1992, pp.31617)

A 1994 examination of 32 English sport/exercise science textbooks found that 7 (21.9%) claimed that there are biophysical differences due to race that might explain differences in sports performance, 24 (75%) did not mention nor refute the concept, and 1 (3.1%) expressed caution with the idea.[173]

In February 2001, the editors of Archives of Pediatrics and Adolescent Medicine asked "authors to not use race and ethnicity when there is no biological, scientific, or sociological reason for doing so."[174] The editors also stated that "analysis by race and ethnicity has become an analytical knee-jerk reflex."[175] Nature Genetics now ask authors to "explain why they make use of particular ethnic groups or populations, and how classification was achieved."[176]

Morning (2008) looked at high school biology textbooks during the 19522002 period and initially found a similar pattern with only 35% directly discussing race in the 198392 period from initially 92% doing so. However, this has increased somewhat after this to 43%. More indirect and brief discussions of race in the context of medical disorders have increased from none to 93% of textbooks. In general, the material on race has moved from surface traits to genetics and evolutionary history. The study argues that the textbooks' fundamental message about the existence of races has changed little.[177]

Surveying views on race in the scientific community in 2008, Morning concluded that biologists had failed to come to a clear consensus, and they often split along cultural and demographic lines. She notes, "At best, one can conclude that biologists and anthropologists now appear equally divided in their beliefs about the nature of race."[167]

Gissis (2008) examined several important American and British journals in genetics, epidemiology and medicine for their content during the 19462003 period. He wrote that "Based upon my findings I argue that the category of race only seemingly disappeared from scientific discourse after World War II and has had a fluctuating yet continuous use during the time span from 1946 to 2003, and has even become more pronounced from the early 1970s on".[178]

33 health services researchers from differing geographic regions were interviewed in a 2008 study. The researchers recognized the problems with racial and ethnic variables but the majority still believed these variables were necessary and useful.[179]

A 2010 examination of 18 widely used English anatomy textbooks found that they all represented human biological variation in superficial and outdated ways, many of them making use of the race concept in ways that were current in 1950s anthropology. The authors recommended that anatomical education should describe human anatomical variation in more detail and rely on newer research that demonstrates the inadequacies of simple racial typologies.[180]

Lester Frank Ward (1841-1913), considered to be one of the founders of American sociology, rejected notions that there were fundamental differences that distinguished one race from another, although he acknowledged that social conditions differed dramatically by race.[181] At the turn of the 20th century, sociologists viewed the concept of race in ways that were shaped by the scientific racism of the 19th and early 20th centuries.[182] Many sociologists focused on African Americans, called Negroes at that time, and claimed that they were inferior to whites. White sociologist Charlotte Perkins Gilman (18601935), for example, used biological arguments to claim the inferiority of African Americans.[182] American sociologist Charles H. Cooley (18641929) theorized that differences among races were "natural," and that biological differences result in differences in intellectual abilities[183][181] Edward Alsworth Ross (1866-1951), also an important figure in the founding of American sociology, and an eugenicist, believed that whites were the superior race, and that there were essential differences in "temperament" among races.[181] In 1910, the Journal published an article by Ulysses G. Weatherly (1865-1940) that called for white supremacy and segregation of the races to protect racial purity.[181]

W. E. B. Du Bois (18681963), one of the first African-American sociologists, was the first sociologist to use sociological concepts and empirical research methods to analyze race as a social construct instead of a biological reality.[182] Beginning in 1899 with his book The Philadelphia Negro, Du Bois studied and wrote about race and racism throughout his career. In his work, he contended that social class, colonialism, and capitalism shaped ideas about race and racial categories. Social scientists largely abandoned scientific racism and biological reasons for racial categorization schemes by the 1930s.[184] Other early sociologists, especially those associated with the Chicago School, joined Du Bois in theorizing race as a socially constructed fact.[184] By 1978, William Julius Wilson argued that race and racial classification systems were declining in significance, and that instead, social class more accurately described what sociologists had earlier understood as race.[185] By 1986, sociologists Michael Omi and Howard Winant successfully introduced the concept of racial formation to describe the process by which racial categories are created.[186] Omi and Winant assert that "there is no biological basis for distinguishing among human groups along the lines of race."[186]

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Race (human categorization) - Wikipedia

The goal of the Graduate Program of the Department of Human Genetics at UCLA is to train the next generation of leaders in human genetics and genomics. This rapidly evolving field of research incorporates multiple areas of modern experimental biology (including but not limited to molecular and behavioral genetics, epigenetics, biochemisty, cell and developmental biology, imaging, and large-scale omics approaches such as genomics, transcriptomics and functional genomics) and of computational biology (including bioinformatics and biostatistics). In their research, students tackle Mendelian diseases and genetically complex traits of key relevance to human health.

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Since its creation in 1998, more than 80 students have graduated from our program. As of September 2020, the average time to degree (defined as the time since admission to graduate school at UCLA, including years spent in other graduate programs) of our Ph.D. Program is 5.31 years. Many of our alumni have published parts of their dissertation work in top scientifc journals and become successful scientists in academy or industry.

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The investigators at the Genetics and Genomics Home Area at UCLA are developing networks, systems, and other multilayer approaches combining large data sets and high-throughput information at genomic, transcriptomics, methylomics, proteomics, metabolomics, and phenome level to address the complex architecture and multiple properties leading to human disease. The overall research emphasis of the Genetics and Genomics Home Area at UCLA is on identification and characterization of genes, pathways, and molecular mechanisms converting human health to a disease, utilizing new and state-of-the-art computational, bioinformatics, and molecular genetic and genomics approaches in an integrative way. Investigation across species, in model organisms, and at the cellular level is also utilized to elucidate fundamental biological principles and disease-causing mechanisms. The broad expertise among the researchers in our Home Area extends from plant, animal, and human molecular genetics and genomics to computational biology and systems genomics.

In our research efforts, we highly value interdisciplinary knowledge and institutional, national, and international collaboration as the core of our success. Translation to novel medical preventative tools and targeted treatments is the key research goal of the studies in the Genetics and Genomics Home Area. We anticipate that these translational and multilayer genomics approaches will soon lay a foundation for personalized medicine that allows interpretation of biological high-throughput data at multiple levels through-out an individuals life in order to tailor preventative measurements and treatments based on his/her genetic, behavioral, and environmental makeup.

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The human Y chromosome harbors genes that are responsible for testis development and also for initiation and maintenance of spermatogenesis in adulthood. The long arm of the Y chromosome (Yq) contains many ampliconic and palindromic sequences making it predisposed to self-recombination during spermatogenesis and hence susceptible to intra-chromosomal deletions. Such deletions lead to copy number variation in genes of the Y chromosome resulting in male infertility. Three common Yq deletions that recur in infertile males are termed as AZF (Azoospermia Factor) microdeletions viz. AZFa, AZFb and AZFc. As estimated from data of nearly 40,000 Y chromosomes, the global prevalence of Yq microdeletions is 7.5% in infertile males; however the European infertile men are less susceptible to Yq microdeletions, the highest prevalence is in Americans and East Asian infertile men. In addition, partial deletions of the AZFc locus have been associated with infertility but the effect seems to be ethnicity dependent. Analysis of > 17,000 Y chromosomes from fertile and infertile men has revealed an association of gr/gr deletion with male infertility in Caucasians and Mongolian men, while the b2/b3 deletion is associated with male infertility in African and Dravidian men. Clinically, the screening for Yq microdeletions would aid the clinician in determining the cause of male infertility and decide a rational management strategy for the patient. As these deletions are transmitted to 100% of male offspring born through assisted reproduction, testing of Yq deletions will allow the couples to make an informed choice regarding the perpetuation of male infertility in future generations. With the emerging data on association of Yq deletions with testicular cancers and neuropsychiatric conditions long term follow-up data is urgently needed for infertile men harboring Yq deletions. If found so, the information will change the current the perspective of androgenetics from infertility and might have broad implication in men health.

Keywords: AZF; AZFc; Infertility; Microdeletions; Prevalence; Spermatogenesis; Y chromosome; gr/gr deletions.

DM is scientist E and Head of Molecular Biology, Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai, India. SC is a post-doctoral fellow, Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai, India.

Not applicable as it is a review article.

Not applicable.

The authors declare that they have no competing interests.

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Fig. 1

Structure of the human Y

Fig. 1

Structure of the human Y chromosome. The Pseudo Autosomal Regions [PAR1 and PAR2]

Structure of the human Y chromosome. The Pseudo Autosomal Regions [PAR1 and PAR2] are located at the terminal ends of the Y chromosome. The green boxes show the genes encoded in these regions. Yp is the short arm of the Y chromosome and the genes within it are show in the peach box. The long arm, Yq, is composed of both euchromatin and the genetically inactive heterochromatin regions. This region contains the Azoospermia factors AZFa, AZFb and AZFc. The pink box shows the genes in the AZFa region. The heterochromatin is not known to harbor any known genes. The region beyond the PAR is termed as Male Specific Region on Y (MSY)

Fig. 2

Schematic organization of the AZFb

Fig. 2

Schematic organization of the AZFb and c loci depicting how the various microdeletions

Schematic organization of the AZFb and c loci depicting how the various microdeletions arise. The AZFb and c regions are located in the euchromatic region on the Yq. Both regions share a number of genes [pink box], the genes present in the AZFb region are shown in the green box while the genes present in the AZFc region are present in the blue box. The grey arrows depict the orientation of the genes and the grey bars depict the organisation of the amplicons into palindromes [P1 to P5]. The AZFb and AZFc loci are composed of numerous stretches of ampliconic sequences [block arrows] which are annotated as six colour-coded sequence families (yellow, blue, turquoise, green, red and grey) called amplicons. The size and orientation of the coloured arrows represents the length and orientation of the arrows. AZFb is defined by the P5/proximal P1 deletion (yel3/yel1) which removes 6.23Mb of DNA and AZFc by the b2/b4 deletion which removes 3.5Mb of DNA. The partial AZFc deletions b1/b3, b2/b3 and the three variations of the gr/gr deletions [g1/g2], [r1/r3] and [r2/r4] [in dotted box] remove almost half of the AZFc gene content. The shaded block depicts the exact location of the deletion. The information of the map is adapted from published data ([6, 27], and [62])

Fig. 3

Expression of RBMY during human

Fig. 3

Expression of RBMY during human spermatogenesis. Human testicular cells were separated by mild

Expression of RBMY during human spermatogenesis. Human testicular cells were separated by mild collagenase digestion, smeared on slides and fixed in acetone. The cells were probed using an antibody against human RBMY (Santacruz Biotechnology Inc., sc 14,572, USA) and detected using a FITC labeled secondary antibody. The cells were imaged under a fluorescent microscope and different stages were identified based on the cell and nuclear size. Green staining represents RBMY, red is nuclei. Bar represents 20m. For details of the methods see Abid et al. [115]

Fig. 4

World map depicting the prevalence

Fig. 4

World map depicting the prevalence of Yq microdeletions in infertile males in different

World map depicting the prevalence of Yq microdeletions in infertile males in different countries. The prevalence of Yq microdeletions in different countries of the world was estimated from published data of 40,127 Y chromosomes from infertile men. (oligozoospermic or azoospermic men). Only those articles published in English were considered and total number of infertile men studied and those having deletions were recorded along with the country. For each country data from different studies were pooled and the average estimated

Fig. 5

Prevalence of Yq microdeletions in

Fig. 5

Prevalence of Yq microdeletions in infertile men. The average prevalence of the Yq

Prevalence of Yq microdeletions in infertile men. The average prevalence of the Yq microdeletions in different continents of the world was estimated from published data of 40,127 Y chromosomes from infertile men. Infertile men could be oligozoospermic or azoospermic men. Pie chart gives distribution of Yq microdeletions in the Asian region. The numbers were estimated from the data of Asian men based on geographical. In both the cases, only those articles published in English were considered and total number of infertile men studied and those having deletions were recorded along with the country. Data from different studies from same continent were pooled and the average estimated (for details see Additional file 1: Table S1)

Fig. 6

Association of gr/gr and b2/b3

Fig. 6

Association of gr/gr and b2/b3 deletions with male infertility. Data was obtained from

Association of gr/gr and b2/b3 deletions with male infertility. Data was obtained from previous studies [105, 126, 167, 188]. Data for gr/gr is derived out of 10,978 and 6704 Y chromosomes from infertile and fertile men respectively. For b2/b3 the data is derived out of 9981 and 5990 Y chromosomes from fertile and infertile men respectively. Infertile men could be oligozoospermic or azoospermic men. Fertile men would be normozoospermic/proven fertile men with unknown sperm counts. Data was divided based on continents or by race. * indicates value significantly different form fertile counterpart

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