Category Archives: Human Genetics

SOUTH SAN FRANCISCO, Calif., Oct. 05, 2022 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (23andMe), a leading human genetics and biopharmaceutical company with a mission to help people access, understand, and benefit from the human genome, today announced that it will present a trials-in-progress poster presentation on 23ME-00610, an investigational antibody targeting CD200R1, at the Society for Immunotherapy of Cancers (SITC) 37th Annual Meeting to be held in Boston, MA from November 812, 2022.

The trials-in-progress poster presentation will summarize the study design for the ongoing first-in-human Phase 1 study assessing the safety, tolerability and preliminary anticancer activity of 23ME-00610,the Company's wholly-owned investigational therapy targeting CD200R1, in patients with advanced solid malignancies. Included in the presentation will be details on the expansion phase of the study (part B) in patients with specific types of advanced solid tumors.

Title: A Phase 1 Dose Escalation and Expansion Study of the anti-CD200R1 Antibody 23ME-00610 in Patients with Advanced Solid Malignancies.Session: Annual Meeting Regular Poster Abstract PresenterAbstract/Poster Number: 758Location: Hall C (The poster will also be available to view under the investors section of the Companys website at investors.23andme.com).Date and Time: Friday, November 11, 2022 - 9:00 a.m. 8:30 p.m. ET

About 23andMe23andMe is a genetics-led consumer healthcare and therapeutics company empowering a healthier future. For more information, please visit http://www.23andMe.com. 23andMe is the only company with multiple FDA authorizations for over-the-counter genetic health risk reports, and in particular the only company FDA authorized to provide, without physician involvement, genetic cancer risk reports and medication insights on how individuals may process certain commonly prescribed medications based on their genetics. The Company has also created the worlds largest crowdsourced platform for genetic research, which it is using to pursue drug discovery programs rooted in human genetics across a spectrum of disease areas.

About 23ME-0061023ME-00610 is a high-affinity humanized monoclonal antibody that is designed to bind to the CD200R1 receptor and prevent the interaction of CD200 and CD200R1. The CD200CD200R1 axis is an immunological checkpoint that plays a pivotal role in maintenance of immune tolerance. CD200R1 is an inhibitory receptor expressed on T cells and myeloid cells while CD200, the ligand for CD200R1, is highly expressed on certain tumors. Binding of tumor associated CD200 to CD200R1 leads to immune suppression and decreased immune cell killing of cancer cells. Preclinical data indicate that this mechanism has the potential to restore the ability for both T-cells and myeloid cells to kill cancer cells.

The Phase 1 study is an open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of 23ME-00610 in patients with advanced solid malignancies who have progressed on all available standard therapies. Clinical trials registry (clinicaltrials.gov): NCT05199272.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including, without limitation, statements regarding the future performance of 23andMes businesses in consumer genetics and therapeutics and the growth and potential of its proprietary research platform. All statements, other than statements of historical fact, included or incorporated in this press release, including statements regarding 23andMes strategy, financial position, funding for continued operations, cash reserves, projected costs, plans, and objectives of management, are forward-looking statements. The words "believes," "anticipates," "estimates," "plans," "expects," "intends," "may," "could," "should," "potential," "likely," "projects," predicts, "continue," "will," schedule, and "would" or, in each case, their negative or other variations or comparable terminology, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on 23andMes current expectations and projections about future events and various assumptions. 23andMe cannot guarantee that it will actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements and you should not place undue reliance on 23andMes forward-looking statements. These forward-looking statements involve a number of risks, uncertainties (many of which are beyond the control of 23andMe), or other assumptions that may cause actual results or performance to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Companys filings with the Securities and Exchange Commission, including under Item 1A, Risk Factors in the Companys most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. The statements made herein are made as of the date of this press release and, except as may be required by law, 23andMe undertakes no obligation to update them, whether as a result of new information, developments, or otherwise.

Contacts: Investor Relations Contact: investors@23andMe.comMedia Contact: press@23andMe.com

See the article here:
23andMe Announces Trials-in-Progress Poster Presentation on 23ME-00610, An Investigational Antibody Targeting CD200R1, at The Society for...

Since the dawn of civilization, people have searched for the secret to long life. Famously, Gianni Pes, Michel Poulain and Dan Buettner proposed that diet drives a persons longevity. Other researchers have favored a genetics based explanation for longevity. Recently, a study published in Science found that a mouses genes determine its lifespan, and that there are human orthologs, or analogous genes. The study also found that female and male mice have different genes controlling their lifespans, which is interesting considering that female mice have longer lifespans. The study firmly lands on the side of those who have argued that genes directly determine lifespan. This means that reducing the risk of disease alone is not enough to increase longevity.

While the idea of aging is universal, in scientific terms, it does not have a precise measure. Much as Socrates asked us to investigate the real meaning of widely discussed concepts, scientists have had to work out ways to measure aging, and, this implies, asking what aging really is. Broadly, as the authors of the study note, it is a progressive decline in physical, mental and reproductive capacities, in which a person accumulates morbidities and the risk of dying increases. However, it is not known what the exact interplay is between genes, sex and environment, in determing lifespan.

Researchers have measured aging through a number of traits, such as lifespan, and age-related disease onset. Researchers believe that if they can figure out what the genetic and nongenetic drivers of longevity are, they can develop treatments to improve not just quality of life, but longevity.

A team of scientists led by Robert Williams, looked at the determinants of longevity in 3276 UM-HET3 mice, a type of, or genetically diverse mice that the National Institute on Agings (NIA) Interventions Testing Program (ITP) had been studying. The NIAs TIP had collected this data in 2003, when they were trying to see if dietary interventions would affect the longevity of mice. The mice were raised in closely controlled, homogeneous conditions, and the program collected tissue from them, so they could isolate the impact of genes on the lifespan of mice. The diversity of mice was a result of the need to mirror the diversity in the human genepool. Typically, mice do tend to inbreed, and this warps studies on longevity.

The NIAs TIP did not study the genetic drivers of longevity, and that is the point at which Robert WIlliams and his team began their study. The team were charged with figuring out whether the genetic drivers of longevity are related to sex and age, and whether the nongenetic drivers, such as litter size, or having a good diet from early in life, was important to longevity. In studying these drivers, they were able to classify the changes in liver gene expression of mice in the same genetic cross, according to whether they were driven by age or genotype. The last step in the study was to bring those results together with the orthogonal or itnesecting datasets, to undertake quantitative trait locus mapping, associating phenotypes with genotypes. This would allow the team to figure out which genes are associated with increased longevity.

The team was able to determine genetic loci important for longevity. Sevel of these loci were found in female mice, but, at first, no genetic loci linked specifically to longevity in male mice, were found. When the scientists removed the data for male mice who died at the beginning of the study, they then found genetic loci associated specifically with longevity in male mice. They also found that the factors such as body weight and litter size also impact longevity. For instance, mice with larger body weights and who grew up in smaller litters, died earlier. Consequently, genes linked to body weight and litter size could arguably be linked to longevity. Longevity could be indirectly impacted by the effect of these genes on those factors. However, it is important to note that not all longevity genes are correlated with those factors, opening up the door to the possibility that there are other genes influencing longevity.

The goal of this study was to say something meaningful about longevity in humans, so the study then went to human genome biobanks, and the researchers found sequences that mirrored those in mice. In addition, there was a similar relationship between early development and longevity. They then looked at genes in worms, to see if a similar relationship existed, and if broader conclusions could be drawn about the association of these genes and longevity. Ultimately, they concluded that genes are the primary determinants of longevity.

Link:
The Genetic Drivers Of Longevity In Mice, Humans And Worms - Science 2.0

Ethics approval and informed consent

All participants provided informed consent, and studies were approved by the individual IRBs at the respective institutions. UK Biobank has approval from the North West Multi-center Research Ethics Committee (MREC), which covers the UK. It also sought the approval in England and Wales from the Patient Information Advisory Group (PIAG) for gaining access to information that would allow it to invite people to participate. The DiscovEHR study was approved by the Institutional Review Board (IRB) at Geisinger. The BioMe Biobank is an ongoing research biorepository approved by the Icahn School of Medicine at Mount Sinais IRB. The Ethical Committee at Lund University approved the Malmo Diet and Cancer Study (LU 5190) and all the participants provided a written informed consent. The CGPS study (H-KF-01-144/01) was approved by the Ethics Committee of the Capital Region and from the Danish Data Protection Agency. Research at Estonian Biobank is regulated by Human Gene Research Act and all participants have signed a broad informed consent. IRB approval for current study was granted by Research Ethics Committee of University of Tartu, approval nr 236/T-23. For the POAAGG study, approval to enroll and to recontact subjects was obtained from the University of Pennsylvania IRB. The Finngen Biobank was evaluated and approved by the Coordinating Ethics Committee of the Helsinki and Uusimaa Hospital District.

Association with IOP was tested on a total of 101,678 individuals and 27,529 individuals of European ancestry from the United Kingdom Biobank (UKB) and the MyCode Community Health Initiative cohort from Geisinger Health System (GHS), respectively. The UKB is a population-based cohort study of people aged between 40 and 69 years recruited through 22 testing centers in the UK between 2006 and 201040. The GHS MyCode study is a health system-based cohort of patients from Central and Eastern Pennsylvania (USA) recruited in 2007201941. For IOP association tests in African ancestry individuals, we included 4114 individuals from UKB and 3167 individuals from the Primary Open Angle African-American Glaucoma Genetics (POAAGG) study conducted at the University of Pennsylvania Perelman School of Medicine42. We excluded all participants with a glaucoma diagnosis code (ICD-10 H40) or self-reported glaucoma (UKB field IDs: 6148 and 20002) from IOP analyses.

Association of ANGPTL7 variants with glaucoma was tested in 8 studies: UKB, GHS, Mt. Sinai BioMe cohort (SINAI), the Malm Diet and Cancer study (MALMO)43, the Estonia Biobank (EstBB)44, The Trndelag Heath Study (HUNT)45, FinnGen, a study from Finland, and the Copenhagen General Population Study and the Copenhagen City Heart Study (CGPS-CCHS)46. We had, in total, up to 40,042 cases (UKB: 12,377, GHS: 8032, SINAI: 409, MALMO: 2395, EstBB: 7629, HUNT: 3874; CPGS-CCHS: 1863; FinnGen: 3463) and 947,782 controls of European ancestry, and 5153 cases (UKB: 448, POAAGG: 3444, SINAI: 1261) and 21,650 controls of African ancestry in glaucoma analyses.

IOP in UKB was measured in each eye using the Ocular Response Analyzer (Reichert Corp., Buffalo, New York). Participants were excluded from this test if they reported having eye surgery in the preceding 4 weeks or having an eye infection. The Ocular Response Analyzer calculates two forms of IOP, a Goldmann-correlated IOP (IOPg) and a corneal-compensated IOP (IOPcc). IOPg most closely approximates the IOP measured by the Goldmann Applanation Tonometer(GAT), which has been the gold standard for measuring IOP, while IOPcc provides a measure of IOP that is adjusted to remove the influence of corneal biomechanics47. For this study, we focused on IOPg as this measurement is the most comparable to IOP measurements in other cohorts, and herein IOPg will be referred to as IOP. IOP in POAAGG was measured using a GAT. In GHS, IOP measurements were obtained from several instruments including GAT, Tono-pen and I-Care, which are correlated with IOPg readings from the Ocular Response Analyzer48. For GHS individuals who were not prescribed any IOP medications, we used the median of all IOP measurements available. For individuals who had an IOP medication prescribed, we used the median of IOP measurements available preceding the start date for IOP medications (if available). Individuals for whom we did not have non-medicated IOP values were excluded from the IOP genetic analyses. For association analyses of IOP, we excluded individuals with: (1) a glaucoma diagnosis; (2) IOP measures that were more than 5 standard deviations away from the mean; (3) more than a 10-mmHg difference between both eyes. We derived a mean IOP measure between both eyes for each individual. IOP of only one eye was used in instances where IOP measures for both eyes were not available.

Details on glaucoma definition in each cohort are given in the Supplementary Methods. In brief, glaucoma cases in GHS, SINAI, MALMO, HUNT, EstBB, FinnGen (v.R3) and CGPS-CCHS were defined by the presence of an ICD-10 H40 diagnosis code in either outpatient or inpatient electronic health records. In UKB, glaucoma cases were defined as individuals with either an ICD-10 H40 diagnosis or self-reported glaucoma (UKB field ID: 6148 or 20002). In the POAAGG cohort, glaucoma cases and controls were classified based on an ophthalmic examination by glaucoma specialists, and glaucoma suspects were also included in the cases42.

High coverage whole exome sequencing and genotyping was performed at the Regeneron Genetics Center49,50 as described in Supplementary Methods. We estimated the association with IOP and glaucoma of genetic variants or their gene burden using REGENIE v1.0.4351 (UKB, GHS, MALMO, SINAI), SAIGE52 (HUNT, EstBB, FinnGen) or logistic regression (CGPS-CCHS). Analyses were adjusted for age, age2, sex, an age-by-sex interaction term, experimental batch-related covariates, and genetic principal components, where appropriate. Cohort-specific statistical analysis details are provided in Supplementary Methods. Results across cohorts were pooled using inverse-variance weighted meta-analysis. Details on the PheWAS analysis conducted in UKB and GHS are provided in Supplementary Methods. Western blotting and ELISA analyses were repeated on three independent biological replicates and data are presented as meanSEM. Technical replicates (n=3) were run for the ELISA analysis. P values were calculated by one-way ANOVA with Tukeys multiple comparison test for multiple groups analysis (Supplementary Data1). A total of 12 eyes were used to test the effect of increasing mAngptl7 levels in mouse eyes and Students t test was used to calculate the significance of the resulting change in IOP. The IOP was measured on 33 WT, 41 Angptl7 KO and 15 Angptl7 Het mice and conventional outflow facility was measured on 4 WT and 7 Angptl7 KO mice. Unpaired Students t-test was used to calculate the statistical significance of the results between the different genotypes. For in vivo siRNA knockdown of mAngptl7, we used 8, 6, 6 and 5 mouse eyes for siRNA#3, siRNA#5, PBS-treated and Nave controls, respectively. Statistical significance was calculated using one-way ANOVA with Dunnetts post hoc analysis (Supplementary Data1).

HEK293 cells, derived within Regeneron, were cultured in DMEM media 4.5g/L D-Glucose, (+) L-Glutamine, () Sodium Phosphate, () Sodium Pyruvate supplemented with 10% FBS and 1% Penicillin-Streptomycin-Glutamine (Invitrogen), at 37C in a humidified atmosphere under 5% CO2. The day before transfection, HEK293 cells were seeded in OptiMEM supplemented with 10% FBS. After 24h, the cells were transfected with FuGENE 6, and 10g of pcDNA 3.1(+) encoding the following proteins: ANGPTL7 WT, Gln175His, Arg177* and Trp188*. After 24h, the media was changed with 2% FBS OptiMEM. The following day, the cells were collected in RIPA buffer, supplemented with protease and phosphatase inhibitors (BRAND) or TRIzol reagent (Invitrogen) for protein and RNA analysis, respectively. The supernatants were transferred to an Eppendorf tube and immediately flash frozen for downstream protein analysis. Western blot analysis was performed using a rabbit polyclonal antibody against ANGPTL7 at 1:1000 dilution (10396-1-AP ProteinTech), using standard procedures. ANGPTL7 was quantified by ELISA according to manufacturers instructions (LS-F50425 Life Sciences). The cell lysates were diluted 1:1000. The supernatants were diluted 1:10,000. The ELISA plate was read at 450nm via SpectraMax M4 plate reader (Molecular Devices).

Total RNA was extracted using TRIzol reagent (Invitrogen) and RNeasy kit (Qiagen) according to manufacturers instructions and treated with RNase-free DNase I (Promega). cDNA was synthesized using Superscript VILO cDNA synthesis kit (Invitrogen). Taqman analysis was performed using TaqMan Fast Advanced Master Mix (Applied Biosystems) in a QuantStudio 6 Flex (Applied Biosystems) and commercially available primers and probes for ANGPTL7 (Hs00221727Applied Biosystems) and GAPDH (Hs02786624_g1Applied Biosystems).

All animal protocols were approved by the Institutional Animal Care and Use Committee in accordance with the Regenerons Institutional Animal Care and Use Committee (IACUC) and the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research. Angptl7/ mice, on 63% C57BL/6NTac and 37% 129SvEvTac background, were generated by Regeneron Pharmaceuticals using the VelociMouse technology53. Heterozygous mice (Angptl7+/) were bred to generate age-matched wild-type, het and KO littermates that were used for experimentation at 3-4 months of age (mixed gender). Ocular anatomy in these mice was characterized using optical coherence tomography. Detailed methods on generation and characterization of KO mice are provided in Supplementary Methods. For in vivo siRNA experiments, we used C57BL/6J male mice, 3-4 months old, from Jackson Labs.

Mice were anesthetized and IOP was measured in both eyes using a TonoLab rebound tonometer (Colonial Medical Supply, Franconia, NH) before the start of Angptl7 injection and every day afterwards for six days54,55,56. When testing Angptl7 siRNAs, IOPs were measured in each eye before then start of experiment and then every week until end of study. IOP measurements for both eyes were completed within 35min. Six correct single measurements were done on each eye to generate one IOP reading. We took five IOP readings for each eye and used the average of those readings at each time-point.

Aqueous humor outflow facility (C) was measured by using our constant flow infusion technique in live mice55,56,57,58. Mice were anesthetized by using a 100/10mg/kg ketamine/xylazine cocktail. A quarter to half of this dose was administered for maintenance of anesthesia as necessary. One to two drops of proparacaine HCl (0.5%) (Bausch+Lomb) were applied topically to both eyes for corneal anesthesia. The anterior chambers of both eyes were cannulated by using a 30-gauge needle inserted through the cornea 12mm anteriorly to the limbus and pushed across the anterior chamber to a point in the chamber angle opposite to the point of cannulation, taking care not to touch the iris, anterior lens capsule epithelium, or corneal endothelium. Each cannulating needle was connected to a previously calibrated (sphygmomanometer, Diagnostix 700; American Diagnostic Corporation, Hauppauge, NY, USA) flow-through BLPR-2 pressure transducer (World Precision Instruments [WPI], Sarasota, FL, USA) for continuous determination of pressure within the perfusion system. A drop of genteal (Alcon) was also administered to each eye to prevent corneal drying. The opposing ends of the pressure transducer were connected via further tubing to a 1ml syringe loaded into a microdialysis infusion pump (SP200I Syringe Pump; WPI). The tubing, transducer, and syringe were all filled with sterile DPBS (Gibco). Signals from each pressure transducer were passed via a TBM4M Bridge Amplifier (WPI) and a Lab-Trax Analog-to-Digital Converter (WPI) to a computer for display on a virtual chart recorder (LabScribe2 software; WPI). Eyes were initially infused at a flow rate of 0.1 l/min. When pressures stabilized within 1030min, pressure measurements were recorded over a 5-min period, and then flow rates were increased sequentially to 0.2, 0.3, 0.4, and 0.5l/min. Three stabilized pressures at 3-minute intervals at each flow rate were recorded. C in each eye of each animal was calculated as the reciprocal of the slope of a plot of mean stabilized pressure as ordinate against flow rate as abscissa.

A 33-gauge needle with a glass microsyringe (5-uL volume; Hamilton Company) was used for injections of Angptl7 protein/siRNA into mice eyes. For intravitreal injections, the eye was proptosed, and the needle was inserted through the equatorial sclera and into the vitreous chamber at an angle of approximately 45 degrees, taking care to avoid touching the posterior part of the lens or the retina. Angptl7 protein (catalog# 4960-AN-025; R&D Systems, Minneapolis, MN) or siRNA (from Alnylam Pharmaceuticals, Supplementary Methods) or PBS (1uL) was injected into the vitreous over the course of 1minute. The needle was then left in place for a further 45s (to facilitate mixing), before being rapidly withdrawn. siRNA sequences for all six probes tested are provided in Table2. Before and during intracameral injections of Angptl7 protein, mice were anesthetized with isoflurane (2.5%) containing oxygen (0.8L/min). For topical anesthesia, both eyes received one to two drops of 0.5% proparacaine HCl (Akorn Inc.). Each eye was proptosed and the needle was inserted through the cornea just above the limbal region and into the anterior chamber at an angle parallel to the cornea, taking care to avoid touching the iris, anterior lens capsule epithelium, or corneal endothelium. Up to 1L of Angptl7 protein or PBS was injected into each eye over a 30-s period before the needle was withdrawn. Only one injection was administered at day 0.

Further information on research design is available in theNature Research Reporting Summary linked to this article.

View original post here:
ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma | Communications Biology - Nature.com

Svante Pbos memoir of how he came to lead a project to sequence the Neanderthal genome Neanderthal Man: In Search of Lost Genomes is at heart about sex. Sex in the sense of sexual behavior, not biological sex.

Sex in the sense of the drawn-out process of discovering whether we, the anatomically modern humans who are the sole survivors of the genus Homo, ever mated and produced children with our extinct nearest relative.

Andlets deal with this first and get it out of the waysex in the sense of Pbos own sex life. His candor about his bisexuality and his lengthy affair with a (female) scientist who also happened to be the wife of a colleague/collaborator who was nearly as well known in evolutionary genetics as Pbo himself. An affair that resulted in a son and marriage on a remote beach in Hawaii. Told with a strong implication that it wasnt that big a deal. That they all lived happily ever after.

A novelty in scientific autobiography, to be sure, and bound to raise more than a few eyebrows. But the candor reveals no drama and recounts no prurient details. Not about his gay life and not about the events leading to that private romantic marriage. Instead, they are matter-of-fact disclosures. Very nearly ho-hum.

This struck me as being fully in line with the trend in public attitudes toward sexual preferences, in the West at least. Which is a shrug and whatever. A revolution, really, but radical chiefly in that it has happened so fast. Fast, but not so fast that it has spilled over into places like Russia and Uganda.

Of course. You dont need to look at genomes to figure that out. [W]hat human groups dont? Pbo asks, rhetorically. So, yes, we had sex with them.

But did we have children with them? Thats the really interesting question. If Neanderthal DNA lives on in us, then it can be said that Neanderthals are not really extinct after all. It could mean we got some useful stuff from them; it would be good to know what it was. And scientists could begin to figure out which genes we possess that they didnt, how and why those genes contributed to the fact that were here, several billion of us, and they are long gone.

There was scientific resistance to this idea of intromission, the decorous term scientists use. Pbo himself doubted it. Thats partly because the first stab at Neanderthal DNA some years ago was to sequence the mitochondrial genome, not the DNA in the cell nucleus. (Nuclear DNA is what we usually mean when we say the genome.) Neanderthal mtDNA turned out to be unlike any human mtDNA around today. Which suggested that Neanderthals had contributed nothing to us.

Mitochondria, generally called the energy powerhouses of a cell, are remnants of bacteria that invaded multicellular organisms billions of years ago and stuck around. (For more on mtDNA, see my GLP article on three-parent babies.) If mtDNA is not the genome, why bother with it? Because, although it contains only 37 genes, there are hundreds and sometimes thousands of copies of it in every cell. Theres only one copy of the genome, the DNA in the cell nucleus. Its much, much easier to recover mtDNA, especially if youre trying to pry fragile DNA from bone thats been lying around in a cave for 40,000 years or more.

Even though Neanderthal mtDNA isnt like ours, the only way to really settle the question of its genetic contribution to us is to look at DNA in the Neanderthal cell nucleus and see if any of it matches our DNA. That horrendous task is mostly what Neanderthal Man is about.

The result: People of European or Asian ancestry have inherited between 1 and 4 percent of their nuclear DNA from Neanderthals, probably from matings that took place in the Middle Eastin present-day Israel, in factbefore the forebears of Europeans and Asians dispersed to the West and East. For technical theoretical reasons, it seems likely that most of these matings involved Neanderthal men with women from what Pbo calls the Replacement Crowd. (Thats us.)

Ive written a number of pieces on ancient DNA, and Ive always known it was tough to find and to analyze. But from Neanderthal Man I learned that I had no idea. DNA can be destroyed easily; ancient bone sources are pretty useless unless theyve been very dry for their thousands of years of storage. It also helps if they are very cold, which is why bones from extinct mammoths have yielded DNA relatively easily. There are no Neanderthals buried in permafrost.

And then theres the contamination problem. Microbes, mostly bacteria, burrow into buried bone and leave their DNA behind. So do the workers who dig up the bones and the museum curators who handle them (and sometimes lick them, a practice that, when he witnessed it himself, nearly caused Pbo to faint dead away.) Recent human DNA contamination is particularly awful because its so similar to Neanderthal DNA; its terribly hard to tell them apart.

And when the scientists finally got probable Neanderthal DNAin their best bone, amounting to only 3 percent of the totalthe tiny fragments had to be run through sequencers hundreds (or thousands) of times to ensure accuracy. The resulting sequences then had to be mapped against contemporary human DNA and ape DNA to figure out where they differ. This, Pbo says, is much like doing a giant jigsaw puzzle with many missing pieces, many damaged pieces, and lots and lots of extra pieces that would fit nowhere in the puzzle.

Im not even going to get in to the computations and programming skills involved in every step, although Pbo explains them quite well even for the mathematically uninclined.

In fact, the explanations of technical matters throughout the book are on the whole admirable. A few scientists write really well, but most dont, and English is not Pbos first language. You wouldnt know it. Some passages made me wonder if a science writer had helped out. Four editors are credited in the brief Preface, but no science writers. Pbo is free with praise and thanks for his many scientific collaborators, so Im inclined to think he would do the same for significant writing help if he had gotten it. I guess thats a compliment, but maybe Im just envious.

Pbo emphasizes how important his lab teams cohesion was to him. He is quite snarky about the two 800-pound gorilla journals, Science and Nature, which have been so eager to be known for hot papers that they have published some dubious ancient DNA studies. (One example is a most unlikely claim to have sequenced dinosaur DNA.) Yet a number of important papers from his lab have appeared there, in part because those venues do the careers of his junior colleagues the most good.

Another example: He and some of his colleagues wanted to patent the Neanderthal genome and license its use elsewhere, especially for use by companies providing DNA sequencing as a consumer product. This money would help fund the labs work. But some in his research group were adamantly opposed, insisting the data should be available freely to all. Pbo bowed to their urgency and gave up the patenting idea.

Cooperation was a hallmark among the many far-flung collaborators too. In the time leading up to publication of the complete Neanderthal genome paper, Pbo feared that the startling news about Neanderthal DNA being found in most of todays humans would leak to reporters. But it never did. Quite remarkable, considering that at least 50 people knew this fascinating fact. That paper, by the way, was nearly book-size. The supplementary material ran to 19 chapters and 174 pages.

Its an interesting question how much the research in Pbos lab (at the Max Planck Institute for Evolutionary Anthropology in Leipzig) was eased along by something most of todays scientists are not vouchsafed: stable support. It came from Germanys Max Planck Society. This is funding that doesnt require the anxiety and hassle of annual grant proposals.

I dont know if this is the real Svante Pbo: driven, obsessive, a team-building natural, honest about his errors and his anxieties and his (very occasional) fits of temper. Often modest. The very model of a modern major scientist, and a very nice guy.

I hope so and have no reason to think otherwise. Personal anecdote: Several years ago an editor introduced a fairly serious error into a piece I had interviewed him for. She then posted the final version before I had a chance to look at it. When I did, I was of course horror-struck. I demanded (and got) an immediate fix, and then, visions of my science journalism career in ruins, wrote Pbo a groveling apology. He replied by return email, amused at my panic, telling me not to worry. Whew!

So, yes, to this n of 1, a very nice guy.

Pbos tale describes a process approaching the Platonic Idea of contemporary science: a lot of very smart people collaboratively working their butts off, persisting through mistakes and failures and numbingly repetitive but essential tasks and political machinations and technological inadequacies because they believe the Truth is Out There. And finally finding it.

Others have not yet weighed in, and this being top-level and therefore monumentally competitive science, contrarians may well emerge. But if the Neanderthal genome project was anything like what Pbo describes, we are damn lucky.

Tabitha M. Powledge is a long-time science journalist and a contributing columnist for the Genetic Literacy Project. She writes On Science Blogs for the PLOS Blogs Network.

This article previously appeared on the GLP March 6, 2014.

Read the original post:
'Neanderthal Man' Nobel Prize winner Svante Pbo revolutionized anthropology. Here is a look back at his groundbreaking 2014 memoir - Genetic Literacy...

Genetics is the scientific study of inherited variation. Human genetics, then, is the scientific study of inherited human variation.

Why study human genetics? One reason is simply an interest in better understanding ourselves. As a branch of genetics, human genetics concerns itself with what most of us consider to be the most interesting species on earth: Homo sapiens. But our interest in human genetics does not stop at the boundaries of the species, for what we learn about human genetic variation and its sources and transmission inevitably contributes to our understanding of genetics in general, just as the study of variation in other species informs our understanding of our own.

A second reason for studying human genetics is its practical value for human welfare. In this sense, human genetics is more an applied science than a fundamental science. One benefit of studying human genetic variation is the discovery and description of the genetic contribution to many human diseases. This is an increasingly powerful motivation in light of our growing understanding of the contribution that genes make to the development of diseases such as cancer, heart disease, and diabetes. In fact, society has been willing in the past and continues to be willing to pay significant amounts of money for research in this area, primarily because of its perception that such study has enormous potential to improve human health. This perception, and its realization in the discoveries of the past 20 years, have led to a marked increase in the number of people and organizations involved in human genetics.

This second reason for studying human genetics is related to the first. The desire to develop medical practices that can alleviate the suffering associated with human disease has provided strong support to basic research. Many basic biological phenomena have been discovered and described during the course of investigations into particular disease conditions. A classic example is the knowledge about human sex chromosomes that was gained through the study of patients with sex chromosome abnormalities. A more current example is our rapidly increasing understanding of the mechanisms that regulate cell growth and reproduction, understanding that we have gained primarily through a study of genes that, when mutated, increase the risk of cancer.

Likewise, the results of basic research inform and stimulate research into human disease. For example, the development of recombinant DNA techniques () rapidly transformed the study of human genetics, ultimately allowing scientists to study the detailed structure and functions of individual human genes, as well as to manipulate these genes in a variety of previously unimaginable ways.

Recombinant techniques have transformed the study of human genetics.

A third reason for studying human genetics is that it gives us a powerful tool for understanding and describing human evolution. At one time, data from physical anthropology (including information about skin color, body build, and facial traits) were the only source of information available to scholars interested in tracing human evolutionary history. Today, however, researchers have a wealth of genetic data, including molecular data, to call upon in their work.

Two research approaches were historically important in helping investigators understand the biological basis of heredity. The first of these approaches, transmission genetics, involved crossing organisms and studying the offsprings' traits to develop hypotheses about the mechanisms of inheritance. This work demonstrated that in some organisms at least, heredity seems to follow a few definite and rather simple rules.

The second approach involved using cytologic techniques to study the machinery and processes of cellular reproduction. This approach laid a solid foundation for the more conceptual understanding of inheritance that developed as a result of transmission genetics. By the early 1900s, cytologists had demonstrated that heredity is the consequence of the genetic continuity of cells by cell division, had identified the gametes as the vehicles that transmit genetic information from one generation to another, and had collected strong evidence for the central role of the nucleus and the chromosomes in heredity.

As important as they were, the techniques of transmission genetics and cytology were not enough to help scientists understand human genetic variation at the level of detail that is now possible. The central advantage that today's molecular techniques offer is that they allow researchers to study DNA directly. Before the development of these techniques, scientists studying human genetic variation were forced to make inferences about molecular differences from the phenotypes produced by mutant genes. Furthermore, because the genes associated with most single-gene disorders are relatively rare, they could be studied in only a small number of families. Many of the traits associated with these genes also are recessive and so could not be detected in people with heterozygous genotypes. Unlike researchers working with other species, human geneticists are restricted by ethical considerations from performing experimental, "at-will" crosses on human subjects. In addition, human generations are on the order of 20 to 40 years, much too slow to be useful in classic breeding experiments. All of these limitations made identifying and studying genes in humans both tedious and slow.

In the last 50 years, however, beginning with the discovery of the structure of DNA and accelerating significantly with the development of recombinant DNA techniques in the mid-1970s, a growing battery of molecular techniques has made direct study of human DNA a reality. Key among these techniques are restriction analysis and molecular recombination, which allow researchers to cut and rejoin DNA molecules in highly specific and predictable ways; amplification techniques, such as the polymerase chain reaction (PCR), which make it possible to make unlimited copies of any fragment of DNA; hybridization techniques, such as fluorescence in situ hybridization, which allow scientists to compare DNA samples from different sources and to locate specific base sequences within samples; and the automated sequencing techniques that today are allowing workers to sequence the human genome at an unprecedented rate.

On the immediate horizon are even more powerful techniques, techniques that scientists expect will have a formidable impact on the future of both research and clinical genetics. One such technique, DNA chip technology (also called DNA microarray technology), is a revolutionary new tool designed to identify mutations in genes or survey expression of tens of thousands of genes in one experiment.

In one application of this technology, the chip is designed to detect mutations in a particular gene. The DNA microchip consists of a small glass plate encased in plastic. It is manufactured using a process similar to the process used to make computer microchips. On its surface, it contains synthetic single-stranded DNA sequences identical to that of the normal gene and all possible mutations of that gene. To determine whether an individual possesses a mutation in the gene, a scientist first obtains a sample of DNA from the person's blood, as well as a sample of DNA that does not contain a mutation in that gene. After denaturing, or separating, the DNA samples into single strands and cutting them into smaller, more manageable fragments, the scientist labels the fragments with fluorescent dyes: the person's DNA with red dye and the normal DNA with green dye. Both sets of labeled DNA are allowed to hybridize, or bind, to the synthetic DNA on the chip. If the person does not have a mutation in the gene, both DNA samples will hybridize equivalently to the chip and the chip will appear uniformly yellow. However, if the person does possess a mutation, the mutant sequence on the chip will hybridize to the patient's sample, but not to the normal DNA, causing it (the chip) to appear red in that area. The scientist can then examine this area more closely to confirm that a mutation is present.

DNA microarray technology is also allowing scientists to investigate the activity in different cell types of thousands of genes at the same time, an advance that will help researchers determine the complex functional relationships that exist between individual genes. This type of analysis involves placing small snippets of DNA from hundreds or thousands of genes on a single microscope slide, then allowing fluorescently labeled mRNA molecules from a particular cell type to hybridize to them. By measuring the fluorescence of each spot on the slide, scientists can determine how active various genes are in that cell type. Strong fluorescence indicates that many mRNA molecules hybridized to the gene and, therefore, that the gene is very active in that cell type. Conversely, no fluorescence indicates that none of the cell's mRNA molecules hybridized to the gene and that the gene is inactive in that cell type.

Although these technologies are still relatively new and are being used primarily for research, scientists expect that one day they will have significant clinical applications. For example, DNA chip technology has the potential to significantly reduce the time and expense involved in genetic testing. This technology or others like it may one day help make it possible to define an individual's risk of developing many types of hereditary cancer as well as other common disorders, such as heart disease and diabetes. Likewise, scientists may one day be able to classify human cancers based on the patterns of gene activity in the tumor cells and then be able to design treatment strategies that are targeted directly to each specific type of cancer.

Homo sapiens is a relatively young species and has not had as much time to accumulate genetic variation as have the vast majority of species on earth, most of which predate humans by enormous expanses of time. Nonetheless, there is considerable genetic variation in our species. The human genome comprises about 3 109 base pairs of DNA, and the extent of human genetic variation is such that no two humans, save identical twins, ever have been or will be genetically identical. Between any two humans, the amount of genetic variationbiochemical individualityis about .1 percent. This means that about one base pair out of every 1,000 will be different between any two individuals. Any two (diploid) people have about 6 106 base pairs that are different, an important reason for the development of automated procedures to analyze genetic variation.

The most common polymorphisms (or genetic differences) in the human genome are single base-pair differences. Scientists call these differences SNPs, for single-nucleotide polymorphisms. When two different haploid genomes are compared, SNPs occur, on average, about every 1,000 bases. Other types of polymorphismsfor example, differences in copy number, insertions, deletions, duplications, and rearrangementsalso occur, but much less frequently.

Notwithstanding the genetic differences between individuals, all humans have a great deal of their genetic information in common. These similarities help define us as a species. Furthermore, genetic variation around the world is distributed in a rather continuous manner; there are no sharp, discontinuous boundaries between human population groups. In fact, research results consistently demonstrate that about 85 percent of all human genetic variation exists within human populations, whereas about only 15 percent of variation exists between populations (). That is, research reveals that Homo sapiens is one continuously variable, interbreeding species. Ongoing investigation of human genetic variation has even led biologists and physical anthropologists to rethink traditional notions of human racial groups. The amount of genetic variation between these traditional classifications actually falls below the level that taxonomists use to designate subspecies, the taxonomic category for other species that corresponds to the designation of race in Homo sapiens. This finding has caused some biologists to call the validity of race as a biological construct into serious question.

Most variation occurs within populations.

Analysis of human genetic variation also confirms that humans share much of their genetic information with the rest of the natural worldan indication of the relatedness of all life by descent with modification from common ancestors. The highly conserved nature of many genetic regions across considerable evolutionary distance is especially obvious in genes related to development. For example, mutations in the patched gene produce developmental abnormalities in Drosophila, and mutations in the patched homolog in humans produce analogous structural deformities in the developing human embryo.

Geneticists have used the reality of evolutionary conservation to detect genetic variations associated with some cancers. For example, mutations in the genes responsible for repair of DNA mismatches that arise during DNA replication are associated with one form of colon cancer. These mismatched repair genes are conserved in evolutionary history all the way back to the bacterium Escherichia coli, where the genes are designated Mutl and Muts. Geneticists suspected that this form of colon cancer was associated with a failure of mismatch repair, and they used the known sequences from the E. coli genes to probe the human genome for homologous sequences. This work led ultimately to the identification of a gene that is associated with increased risk for colon cancer.

Almost all human genetic variation is relatively insignificant biologically; that is, it has no adaptive significance. Some variation (for example, a neutral mutation) alters the amino acid sequence of the resulting protein but produces no detectable change in its function. Other variation (for example, a silent mutation) does not even change the amino acid sequence. Furthermore, only a small percentage of the DNA sequences in the human genome are coding sequences (sequences that are ultimately translated into protein) or regulatory sequences (sequences that can influence the level, timing, and tissue specificity of gene expression). Differences that occur elsewhere in the DNAin the vast majority of the DNA that has no known functionhave no impact.

Some genetic variation, however, can be positive, providing an advantage in changing environments. The classic example from the high school biology curriculum is the mutation for sickle hemoglobin, which in the heterozygous state provides a selective advantage in areas where malaria is endemic.

More recent examples include mutations in the CCR5 gene that appear to provide protection against AIDS. The CCR5 gene encodes a protein on the surface of human immune cells. HIV, the virus that causes AIDS, infects immune cells by binding to this protein and another protein on the surface of those cells. Mutations in the CCR5 gene that alter its level of expression or the structure of the resulting protein can decrease HIV infection. Early research on one genetic variant indicates that it may have risen to high frequency in Northern Europe about 700 years ago, at about the time of the European epidemic of bubonic plague. This finding has led some scientists to hypothesize that the CCR5 mutation may have provided protection against infection by Yersinia pestis, the bacterium that causes plague. The fact that HIV and Y. pestis both infect macrophages supports the argument for selective advantage of this genetic variant.

The sickle cell and AIDS/plague stories remind us that the biological significance of genetic variation depends on the environment in which genes are expressed. It also reminds us that differential selection and evolution would not proceed in the absence of genetic variation within a species.

Some genetic variation, of course, is associated with disease, as classic single-gene disorders such as sickle cell disease, cystic fibrosis, and Duchenne muscular dystrophy remind us. Increasingly, research also is uncovering genetic variations associated with the more common diseases that are among the major causes of sickness and death in developed countriesdiseases such as heart disease, cancer, diabetes, and psychiatric disorders such as schizophrenia and bipolar disease (manic-depression). Whereas disorders such as cystic fibrosis or Huntington disease result from the effects of mutation in a single gene and are evident in virtually all environments, the more common diseases result from the interaction of multiple genes and environmental variables. Such diseases therefore are termed polygenic and multifactorial. In fact, the vast majority of human traits, diseases or otherwise, are multifactorial.

The genetic distinctions between relatively rare single-gene disorders and the more common multifactorial diseases are significant. Genetic variations that underlie single-gene disorders generally are relatively recent, and they often have a major, detrimental impact, disrupting homeostasis in significant ways. Such disorders also generally exact their toll early in life, often before the end of childhood. In contrast, the genetic variations that underlie common, multifactorial diseases generally are of older origin and have a smaller, more gradual effect on homeostasis. They also generally have their onset in adulthood. The last two characteristics make the ability to detect genetic variations that predispose/increase risk of common diseases especially valuable because people have time to modify their behavior in ways that can reduce the likelihood that the disease will develop, even against a background of genetic predisposition.

As noted earlier, one of the benefits of understanding human genetic variation is its practical value for understanding and promoting health and for understanding and combating disease. We probably cannot overestimate the importance of this benefit. First, as shows, virtually every human disease has a genetic component. In some diseases, such as Huntington disease, Tay-Sachs disease, and cystic fibrosis, this component is very large. In other diseases, such as cancer, diabetes, and heart disease, the genetic component is more modest. In fact, we do not typically think of these diseases as "genetic diseases," because we inherit not the certainty of developing a disease, but only a predisposition to developing it.

Virtually all human diseases, except perhaps trauma, have a genetic component.

In still other diseases, the genetic component is very small. The crucial point, however, is that it is there. Even infectious diseases, diseases that we have traditionally placed in a completely different category than genetic disorders, have a real, albeit small, genetic component. For example, as the CCR5 example described earlier illustrates, even AIDS is influenced by a person's genotype. In fact, some people appear to have genetic resistance to HIV infection as a result of carrying a variant of the CCR5 gene.

Second, each of us is at some genetic risk, and therefore can benefit, at least theoretically, from the progress scientists are making in understanding and learning how to respond to these risks. Scientists estimate that each of us carries between 5 and 50 mutations that carry some risk for disease or disability. Some of us may not experience negative consequences from the mutations we carry, either because we do not live long enough for it to happen or because we may not be exposed to the relevant environmental triggers. The reality, however, is that the potential for negative consequences from our genes exists for each of us.

How is modern genetics helping us address the challenge of human disease? As shows, modern genetic analysis of a human disease begins with mapping and cloning the associated gene or genes. Some of the earliest disease genes to be mapped and cloned were the genes associated with Duchenne muscular dystrophy, retinoblastoma, and cystic fibrosis. More recently, scientists have announced the cloning of genes for breast cancer, diabetes, and Parkinson disease.

Mapping and cloning a gene can lead to strategies that reduce the risk of disease (preventive medicine); guidelines for prescribing drugs based on a person's genotype (pharmacogenomics); procedures that alter the affected gene (gene therapy); or drugs (more...)

As also shows, mapping and cloning a disease-related gene opens the way for the development of a variety of new health care strategies. At one end of the spectrum are genetic tests intended to identify people at increased risk for the disease and recognize genotypic differences that have implications for effective treatment. At the other end are new drug and gene therapies that specifically target the biochemical mechanisms that underlie the disease symptoms or even replace, manipulate, or supplement nonfunctional genes with functional ones. Indeed, as suggests, we are entering the era of molecular medicine.

Genetic testing is not a new health care strategy. Newborn screening for diseases like PKU has been going on for 30 years in many states. Nevertheless, the remarkable progress scientists are making in mapping and cloning human disease genes brings with it the prospect for the development of more genetic tests in the future. The availability of such tests can have a significant impact on the way the public perceives a particular disease and can also change the pattern of care that people in affected families might seek and receive. For example, the identification of the BRCA1 and BRCA2 genes and the demonstration that particular variants of these genes are associated with an increased risk of breast and ovarian cancer have paved the way for the development of guidelines and protocols for testing individuals with a family history of these diseases. BRCA1, located on the long arm of chromosome 17, was the first to be isolated, and variants of this gene account for about 50 percent of all inherited breast cancer, or about 5 percent of all breast cancer. Variants of BRCA2, located on the long arm of chromosome 13, appear to account for about 30 to 40 percent of all inherited breast cancer. Variants of these genes also increase slightly the risk for men of developing breast, prostate, or possibly other cancers.

Scientists estimate that hundreds of thousands of women in the United States have 1 of hundreds of significant mutations already detected in the BRCA1 gene. For a woman with a family history of breast cancer, the knowledge that she carries one of the variants of BRCA1 or BRCA2 associated with increased risk can be important information. If she does carry one of these variants, she and her physician can consider several changes in her health care, such as increasing the frequency of physical examinations; introducing mammography at an earlier age; and even having prophylactic mastectomy. In the future, drugs may also be available that decrease the risk of developing breast cancer.

The ability to test for the presence in individuals of particular gene variants is also changing the way drugs are prescribed and developed. A rapidly growing field known as pharmacogenomics focuses on crucial genetic differences that cause drugs to work well in some people and less well, or with dangerous adverse reactions, in others. For example, researchers investigating Alzheimer disease have found that the way patients respond to drug treatment can depend on which of three genetic variants of the ApoE (Apolipoprotein E) gene a person carries. Likewise, some of the variability in children's responses to therapeutic doses of albuterol, a drug used to treat asthma, was recently linked to genotypic differences in the beta-2-adrenergic receptor. Because beta-2-adrenergic receptor agonists (of which albuterol is one) are the most widely used agents in the treatment of asthma, these results may have profound implications for understanding the genetic factors that determine an individual's response to asthma therapy.

Experts predict that increasingly in the future, physicians will use genetic tests to match drugs to an individual patient's body chemistry, so that the safest and most effective drugs and dosages can be prescribed. After identifying the genotypes that determine individual responses to particular drugs, pharmaceutical companies also likely will set out to develop new, highly specific drugs and revive older ones whose effects seemed in the past too unpredictable to be of clinical value.

Knowledge of the molecular structure of disease-related genes also is changing the way researchers approach developing new drugs. A striking example followed the discovery in 1989 of the gene associated with cystic fibrosis (CF). Researchers began to study the function of the normal and defective proteins involved in order to understand the biochemical consequences of the gene's variant forms and to develop new treatment strategies based on that knowledge. The normal protein, called CFTR for cystic fibrosis transmembrane conductance regulator, is embedded in the membranes of several cell types in the body, where it serves as a channel, transporting chloride ions out of the cells. In CF patients, depending on the particular mutation the individual carries, the CFTR protein may be reduced or missing from the cell membrane, or may be present but not function properly. In some mutations, synthesis of CFTR protein is interrupted, and the cells produce no CFTR molecules at all.

Although all of the mutations associated with CF impair chloride transport, the consequences for patients with different mutations vary. For example, patients with mutations causing absent or markedly reduced CFTR protein may have more severe disease than patients with mutations in which CFTR is present but has altered function. The different mutations also suggest different treatment strategies. For example, the most common CF-related mutation (called delta F508) leads to the production of protein molecules (called delta F508 CFTR) that are misprocessed and are degraded prematurely before they reach the cell membrane. This finding suggests that drug treatments that would enhance transport of the defective delta F508 protein to the cell membrane or prevent its degradation could yield important benefits for patients with delta F508 CFTR.

Finally, the identification, cloning, and sequencing of a disease-related gene can open the door to the development of strategies for treating the disease using the instructions encoded in the gene itself. Collectively referred to as gene therapy, these strategies typically involve adding a copy of the normal variant of a disease-related gene to a patient's cells. The most familiar examples of this type of gene therapy are cases in which researchers use a vector to introduce the normal variant of a disease-related gene into a patient's cells and then return those cells to the patient's body to provide the function that was missing. This strategy was first used in the early 1990s to introduce the normal allele of the adenosine deaminase (ADA) gene into the body of a little girl who had been born with ADA deficiency. In this disease, an abnormal variant of the ADA gene fails to make adenosine deaminase, a protein that is required for the correct functioning of T-lymphocytes.

Although researchers are continuing to refine this general approach to gene therapy, they also are developing new approaches. For example, scientists hope that one very new strategy, called chimeraplasty, may one day be used to actually correct genetic defects that involve only a single base change. Chimeraplasty uses specially synthesized molecules that base pair with a patient's DNA and stimulate the cell's normal DNA repair mechanisms to remove the incorrect base and substitute the correct one. At this point, chimeraplasty is still in early development and the first clinical trials are about to get underway.

Yet another approach to gene therapy involves providing new or altered functions to a cell through the introduction of new genetic information. For example, recent experiments have demonstrated that it is possible, under carefully controlled experimental conditions, to introduce genetic information into cancer cells that will alter their metabolism so that they commit suicide when exposed to a normally innocuous environmental trigger. Researchers are also using similar experiments to investigate the feasibility of introducing genetic changes into cells that will make them immune to infection by HIV. Although this research is currently being done only in nonhuman primates, it may eventually benefit patients infected with HIV.

As indicates, the Human Genome Project (HGP) has significantly accelerated the pace of both the discovery of human genes and the development of new health care strategies based on a knowledge of a gene's structure and function. The new knowledge and technologies emerging from HGP-related research also are reducing the cost of finding human genes. For example, the search for the gene associated with cystic fibrosis, which ended in 1989, before the inception of the HGP, required more than eight years and $50 million. In contrast, finding a gene associated with a Mendelian disorder now can be accomplished in less than a year at a cost of approximately $100,000.

The last few years of research into human genetic variation also have seen a gradual transition from a primary focus on genes associated with single-gene disorders, which are relatively rare in the human population, to an increasing focus on genes associated with multifactorial diseases. Because these diseases are not rare, we can expect that this work will affect many more people. Understanding the genetic and environmental bases for these multifactorial diseases also will lead to increased testing and the development of new interventions that likely will have an enormous effect on the practice of medicine in the next century.

What are the implications of using our growing knowledge of human genetic variation to improve personal and public health? As noted earlier, the rapid pace of the discovery of genetic factors in disease has improved our ability to predict the risk of disease in asymptomatic individuals. We have learned how to prevent the manifestations of some of these diseases, and we are developing the capacity to treat others.

Yet, much remains unknown about the benefits and risks of building an understanding of human genetic variation at the molecular level. While this information would have the potential to dramatically improve human health, the architects of the HGP realized that it also would raise a number of complex ethical, legal, and social issues. Thus, in 1990 they established the Ethical, Legal, and Social Implications (ELSI) program to anticipate and address the ethical, legal, and social issues that arise from human genetic research. This program, perhaps more than any other, has focused public attention, as well as the attention of educators, on the increasing importance of preparing citizens to understand and contribute to the ongoing public dialogue related to advances in genetics.

Ethics is the study of right and wrong, good and bad. It has to do with the actions and character of individuals, families, communities, institutions, and societies. During the last two and one-half millennia, Western philosophy has developed a variety of powerful methods and a reliable set of concepts and technical terms for studying and talking about the ethical life. Generally speaking, we apply the terms "right" and "good" to those actions and qualities that foster the interests of individuals, families, communities, institutions, and society. Here, an "interest" refers to a participant's share or participation in a situation. The terms "wrong" or "bad" apply to those actions and qualities that impair interests.

Ethical considerations are complex, multifaceted, and raise many questions. Often, there are competing, well-reasoned answers to questions about what is right and wrong, and good and bad, about an individual's or group's conduct or actions. Typically, these answers all involve appeals to values. A value is something that has significance or worth in a given situation. One of the exciting events to witness in any discussion in ethics is the varying ways in which the individuals involved assign values to things, persons, and states of affairs. Examples of values that students may appeal to in a discussion about ethics include autonomy, freedom, privacy, sanctity of life, religion, protecting another from harm, promoting another's good, justice, fairness, relationships, scientific knowledge, and technological progress.

Acknowledging the complex, multifaceted nature of ethical discussions is not to suggest that "anything goes." Experts generally agree on the following features of ethics. First, ethics is a process of rational inquiry. It involves posing clearly formulated questions and seeking well-reasoned answers to those questions. For example, we can ask questions about an individual's right to privacy regarding personal genetic information; we also can ask questions about the appropriateness of particular uses of gene therapy. Well-reasoned answers to such questions constitute arguments. Ethical analysis and argument, then, result from successful ethical inquiry.

Second, ethics requires a solid foundation of information and rigorous interpretation of that information. For example, one must have a solid understanding of biology to evaluate the recent decision by the Icelandic government to create a database that will contain extensive genetic and medical information about the country's citizens. A knowledge of science also is needed to discuss the ethics of genetic screening or of germ-line gene therapy. Ethics is not strictly a theoretical discipline but is concerned in vital ways with practical matters.

Third, discussions of ethical issues often lead to the identification of very different answers to questions about what is right and wrong and good and bad. This is especially true in a society such as our own, which is characterized by a diversity of perspectives and values. Consider, for example, the question of whether adolescents should be tested for late-onset genetic conditions. Genetic testing centers routinely withhold genetic tests for Huntington disease (HD) from asymptomatic patients under the age of 18. The rationale is that the condition expresses itself later in life and, at present, treatment is unavailable. Therefore, there is no immediate, physical health benefit for a minor from a specific diagnosis based on genetic testing. In addition, there is concern about the psychological effects of knowing that later in life one will get a debilitating, life-threatening condition. Teenagers can wait until they are adults to decide what and when they would like to know. In response, some argue that many adolescents and young children do have sufficient autonomy in consent and decision making and may wish to know their future. Others argue that parents should have the right to have their children tested, because parents make many other medical decisions on behalf of their children. This example illustrates how the tools of ethics can bring clarity and rigor to discussions involving values.

One of the goals of this module is to help students see how understanding science can help individuals and society make reasoned decisions about issues related to genetics and health. Activity 5, Making Decisions in the Face of Uncertainty, presents students with a case of a woman who is concerned that she may carry an altered gene that predisposes her to breast and ovarian cancer. The woman is faced with numerous decisions, which students also consider. Thus, the focus of Activity 5 is prudential decision making, which involves the ability to avoid unnecessary risk when it is uncertain whether an event actually will occur. By completing the activity, students understand that uncertainty is often a feature of questions related to genetics and health, because our knowledge of genetics is incomplete and constantly changing. In addition, students see that making decisions about an uncertain future is complex. In simple terms, students have to ask themselves, "How bad is the outcome and how likely is it to occur?" When the issues are weighed, different outcomes are possible, depending on one's estimate of the incidence of the occurrence and how much burden one attaches to the risk.

Clearly, science as well as ethics play important roles in helping individuals make choices about individual and public health. Science provides evidence that can help us understand and treat human disease, illness, deformity, and dysfunction. And ethics provides a framework for identifying and clarifying values and the choices that flow from these values. But the relationships between scientific information and human choices, and between choices and behaviors, are not straightforward. In other words, human choice allows individuals to choose against sound knowledge, and choice does not require action.

Nevertheless, it is increasingly difficult to deny the claims of science. We are continually presented with great amounts of relevant scientific and medical knowledge that is publicly accessible. As a consequence, we can think about the relationships between knowledge, choice, behavior, and human welfare in the following ways:

One of the goals of this module is to encourage students to think in terms of these relationships, now and as they grow older.

Biological Sciences Curriculum Study. Teaching tools. Dubuque, IA: Kendall/Hunt Publishing Company; 1999.

Bonwell CC, Eison JA. Washington, DC: The George Washington University: School of Education and Human Development; Active learning: Creating excitement in the classroom. 1991 (ASHE-ERIC Higher Education Report No. 1)

Brody CM. Collaborative or cooperative learning? Complementary practices for instructional reform. The Journal of Staff, Program, & Organizational Development. 1995;12(3):134143.

Harrison GA, Tanner JM, Pilbeam DR, Baker PT. Human biology: An introduction to human evolution, variation, growth, and adaptability. New York: Oxford University Press; 1988.

Knapp MS, Shields PM, Turnbull BJ. Academic challenge in high-poverty classrooms. Phi Delta Kappan. 1995;76(10):770776.

Lander ES. Array of hope. Supplement to nature genetics. 1999 January;21

Moore JA. Science as a way of knowing: The foundations of modern biology. Cambridge, MA: Harvard University Press; 1993.

National Institutes of Health. Congressional justification. Bethesda, MD: Author; 1996.

National Research Council. National science education standards. Washington, DC: National Academy Press; 1996.

Perkins D. Smart schools: Better thinking and learning for every child. New York: The Free Press; 1992.

Project Kaleidoscope. What works: Building natural science communities. Vol. 1. Washington, DC: Stamats Communications, Inc; 1991.

Roblyer MD, Edwards J, Havriluk MA. Integrating educational technology into teaching. Upper Saddle River, NJ: Prentice-Hall, Inc; 1997.

Saltus R. Tailor-made drugs. The Boston Globe. 1998 April 20;

Saunders WL. The constructivist perspective: Implications and teaching strategies for science. School Science and Mathematics. 1992;92(3):136141.

Sizer TR. Horace's school: Redesigning the American high school. New York: Houghton Mifflin Co; 1992.

Vogel F, Motulsky AG. Human genetics: Problems and approaches. 3rd ed. New York: Springer; 1997.

The following glossary was modified from the glossary on the National Human Genome Research Institute's Web site, available at http://www.nhgri.nih.gov.

One of the variant forms of a gene at a particular locus, or location, on a chromosome. Different alleles produce variation in inherited characteristics such as hair color or blood type. In an individual, one form of the allele (the dominant one) may be expressed more than another form (the recessive one).

One of 20 different kinds of small molecules that link together in long chains to form proteins. Amino acids are referred to as the "building blocks" of proteins.

Gene on one of the autosomes that, if present, will almost always produce a specific trait or disease. The chance of passing the gene (and therefore the disease) to children is 50-50 in each pregnancy.

Chromosome other than a sex chromosome. Humans have 22 pairs of autosomes.

Two bases that form a "rung of the DNA ladder." The bases are the "letters" that spell out the genetic code. In DNA, the code letters are A, T, G, and C, which stand for the chemicals adenine, thymine, guanine, and cytosine, respectively. In base pairing, adenine always pairs with thymine, and guanine always pairs with cytosine.

Defect present at birth, whether caused by mutant genes or by prenatal events that are not genetic.

First breast cancer genes to be identified. Mutated forms of these genes are believed to be responsible for about one-half the cases of inherited breast cancer, especially those that occur in younger women, and also to increase a woman's risk for ovarian cancer. Both are tumor suppressor genes.

Diseases in which abnormal cells divide and grow unchecked. Cancer can spread from its original site to other parts of the body and can be fatal if not treated adequately.

Gene, located in a chromosome region suspected of being involved in a disease, whose protein product suggests that it could be the disease gene in question.

Mutation that confers immunity to infection by HIV. The mutation alters the structure of a receptor on the surface of macrophages such that HIV cannot enter the cell.

Collection of DNA sequences generated from mRNA sequences. This type of library contains only protein-coding DNA (genes) and does not include any noncoding DNA.

Basic unit of any living organism. It is a small, watery, compartment filled with chemicals and a complete copy of the organism's genome.

One of the thread like "packages" of genes and other DNA in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes, 46 in all: 44 autosomes and two sex chromosomes. Each parent contributes one chromosome to each pair, so children get one-half of their chromosomes from their mothers and one-half from their fathers.

Process of making copies of a specific piece of DNA, usually a gene. When geneticists speak of cloning, they do not mean the process of making genetically identical copies of an entire organism.

Three bases in a DNA or RNA sequence that specify a single amino acid.

Hereditary disease whose symptoms usually appear shortly after birth. They include faulty digestion, breathing difficulties and respiratory infections due to mucus accumulation, and excessive loss of salt in sweat. In the past, cystic fibrosis was almost always fatal in childhood, but treatment is now so improved that patients commonly live to their 20s and beyond.

Visual appearance of a chromo some when stained and examined under a microscope. Particularly important are visually distinct regions, called light and dark bands, that give each of the chromosomes a unique appearance. This feature allows a person's chromosomes to be studied in a clinical test known as a karyotype, which allows scientists to look for chromosomal alterations.

Particular kind of mutation: loss of a piece of DNA from a chromosome. Deletion of a gene or part of a gene can lead to a disease or abnormality.

Chemical inside the nucleus of a cell that carries the genetic instructions for making living organisms.

Number of chromosomes in most cells except the gametes. In humans, the diploid number is 46.

Technology that identifies mutations in genes. It uses small glass plates that contain synthetic single-stranded DNA sequences identical to those of a normal gene.

Process by which the DNA double helix unwinds and makes an exact copy of itself.

Determining the exact order of the base pairs in a segment of DNA.

Gene that almost always results in a specific physical characteristic (for example, a disease) even though the patient's genome possesses only one copy. With a dominant gene, the chance of passing on the gene (and therefore the disease) to children is 50-50 in each pregnancy.

Structural arrangement of DNA, which looks something like an immensely long ladder twisted into a helix, or coil. The sides of the "ladder" are formed by a backbone of sugar and phosphate molecules, and the "rungs" consist of nucleotide bases joined weakly in the middle by hydrogen bonds.

Particular kind of mutation: production of one or more copies of any piece of DNA, including a gene or even an entire chromosome.

Process in which molecules (such as proteins, DNA, or RNA fragments) can be separated according to size and electrical charge by applying an electric current to them. The current forces the molecules through pores in a thin layer of gel, a firm, jellylike substance. The gel can be made so that its pores are just the right dimensions for separating molecules within a specific range of sizes and shapes. Smaller fragments usually travel further than large ones. The process is sometimes called gel electrophoresis.

See the rest here:
Understanding Human Genetic Variation - NCBI Bookshelf

Why do scientists study the genes of other organisms?

All living things evolved from a common ancestor. Therefore, humans, animals, and other organisms share many of the same genes, and the molecules made from them function in similar ways.

Scientists have found many genes that have been preserved through millions of years of evolution and are present in a range of organisms living today. They can study these preserved genes and compare the genomes of different species to uncover similarities and differences that improve their understanding of how human genes function and are controlled. This knowledge helps researchers develop new strategies to treat and prevent human disease. Scientists also study the genes of bacteria, viruses, and fungi for solutions to prevent or treat infection. Increasingly, these studies are offering insight into how microbes on and in the body affect our health, sometimes in beneficial ways.

Increasingly sophisticated tools and techniques are allowing NIGMS-funded scientists to ask more precise questions about the genetic basis of biology. For example, theyre studying the factors that control when genes are active, the mechanisms DNA uses to repair broken or damaged segments, and the complex ways traits are passed to future generations. Another focus of exploration involves tracing genetic variation over time to detail human evolutionary history and to pinpoint the emergence of disease-related attributes. These areas of basic research will continue to build a strong foundation for more disease-targeted studies.

Here is the original post:
Genetics - National Institute of General Medical Sciences (NIGMS)

People who have been diagnosed with myalgic encephalomyelitis (ME) are being invited to take part in the worlds largest genetic study of the disease.

The study, named DecodeME and led by researchers at Edinburgh Universitys MRC Human Genetics Unit, aims to reveal the tiny differences in a persons DNA that can increase their risk of developing ME, also known as chronic fatigue syndrome (CFS).

It is estimated that more than 250,000 people in the UK are affected by the condition, with symptoms including pain, brain fog and extreme exhaustion that cannot be improved with rest.

The causes of the disease are still unknown, and there is no diagnostic test or effective treatments thus far.

Testing DNA in the saliva of 20,000 donated samples will allow for analysis on whether the disease is partly genetic, and if so, research into its cause and effective treatments.

The study has also been expanded to include analysis on the DNA of a further 5,000 people who have been diagnosed with ME or CFS after having Covid-19.

We believe the results should help identify genes, biological molecules and types of cells that may play a part in causing ME/CFS

Professor Chris Ponting

Along with the DNA research, an anonymous survey will provide an insight into the experience of those with the condition.

The research team is being led by Professor Chris Ponting.

He said: This is the first sizable DNA study of ME/CFS, and any differences we find compared to control samples will serve as important biological clues.

Specifically, we believe the results should help identify genes, biological molecules and types of cells that may play a part in causing ME/CFS.

The university is working alongside charity Action for ME, the Forward ME alliance of UK charities, and people with lived experience of the condition.

Chief executive of Action for ME Sonya Chowdhury said: People with lived experience of ME/CFS are at the very heart of the DecodeME project and our Patient and Participant Involvement group has worked closely with researchers on all aspects of the study.

Their profound involvement has been so transformational that we firmly believe it sets a new standard for health research in this country.

Individuals with ME or CFS who are aged 16 and over and based in the UK are invited to take part from home by signing up on the DecodeME website from 12pm on Monday.

See more here:
People with ME invited to take part in major genetic study - The Independent

Ketamine may be an effective treatment for children with activity-dependent neuroprotective protein (ADNP) syndrome, a rare genetic condition associated with intellectual disability and autism spectrum disorder.

Also known as HelsmoortelVan Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.

Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai in New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.

Using parent-report instruments to assess treatment effects, ketamine was associated with "nominally significant" improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.

Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global ImpressionsImprovement scale.

The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.

The study was published online August 27 in Human Genetics and Genomic (HGG) Advances.

Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).

Treatment emergent AEs were all mild to moderate and no child required any interventions.

The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.

Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).

The researchers caution that the findings are intended to be "hypothesis generating."

"We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome," Kolevzon said in a news release from Mount Sinai.

Ketamine might help ease symptoms of ADNP syndrome "by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways," Kolevzon told Medscape Medical News.

The next step, he said, is to get "a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application."

Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.

HGG Advances. Published online August 27, 2022. Full text

For more Medscape Psychiatry news, join us on Twitter and Facebook

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

See the rest here:
Ketamine Promising for Rare Condition Linked to Autism - Medscape

Jesse Weber collects stickleback with a minnow trap in the Kenai Peninsula of Alaska. Photo by Matt Chotlos

At first blush, sticklebacks might seem a bit pedestrian. The finger-length, unassuming fish with a few small dorsal spines are a ubiquitous presence in oceans and coastal watersheds around the northern hemisphere. But these small creatures are also an excellent subject for investigating the complex dance of evolutionary adaptations.

A new study published Sept. 8 in Science sheds light on the genetic basis by which stickleback populations inhabiting ecosystems near each other developed a strong immune response to tapeworm infections, and how some populations later came to tolerate the parasites.

Evolutionary biologist Jesse Weber, a professor of integrative biology at the University of WisconsinMadison, is one of the studys lead authors. Sticklebacks have long been a source of fascination not only for Weber, but for biologists all over the world so much so that the fish are among the most closely studied species.

An aerial view of an experiment in the Kenai Peninsula of Alaska studying changes in stickleback traits in response to a new environment. Photo by Andrew Hendry

We arguably know more about stickleback ecology and evolution than any other vertebrate, says Weber.

This is in part because of sticklebacks rich abundance in places like Western Europe, where the fish have long been involved in biological study, Weber says. But the reasons for the species star status go well beyond happenstance.

Sticklebacks are also just super charismatic, Weber adds, noting the species complex courtship and territorial behaviors, as well as their diverse colors, shapes and sizes, all of which vary depending on the specific ecosystem they inhabit.

While sticklebacks diversity provides a foothold for understanding why animals evolve different traits, their value for scientists like Weber is boosted by their genetics. The fish have approximately as many genes as humans, but their genetic material is packed much more tightly sticklebacks genome is about one-sixth the size of the human genome.

Their genome is amazingly useful, Weber says. As far as we can tell, its just packed more densely. This means we can efficiently investigate their genetic diversity, allowing us to ask not only, Why do new traits evolve? but also, How are adaptations programmed into the genome?'

On top of all that, sticklebacks take well to captive breeding. A single female can produce hundreds of offspring multiple times over the course of just a few months.

All these traits make stickleback an almost uniquely valuable species for studying the genetic basis for many types of biological adaptations. So, when Weber arrived at UWMadison in the fall of 2020 from the University of Alaska Anchorage, he came with an entire fish colony in tow. Living in tanks, the colony contains fish from genetically distinct populations originating from different lakes and estuaries dotting northwestern North America.

A three spine stickleback with tapeworms recently dissected from the body of the same animal. Photo by Natalie Steinel

In their quest to understand why and how the fish sometimes evolve to look and behave very differently even in relatively nearby lake systems, Weber and his colleagues can crossbreed these populations in various ways and map changes to their genomes across multiple generations relatively quickly.

Much of Webers scientific career to this point has focused on developing tools to make this type of work more efficient. More recently, Weber has turned to using these tools to investigate coevolution the process by which two species adapt to the presence of one another within a shared habitat.

Specifically, Weber and his colleagues have sought to understand why sticklebacks in some lakes are much more likely to be infected with tapeworms than their counterparts in nearby lakes where the tapeworms are also present.

These investigations are beginning to bear fruit. Weber, along with colleagues at the University of Connecticut and University of Massachusetts Lowell, recently identified key genetic differences between the populations.

These differences indicate that all fish populations developed a robust immune response to the tapeworms when they first moved from the sea to new freshwater habitats near the end of the last ice age. But the immune response is costly in terms of both energy and reproduction. It also leads to a large amount of inflammation and internal scarring.

Webers work and that of his colleagues suggest that numerous populations eventually evolved to avoid these costs by ignoring, or in the lingo of immunologists tolerating, the parasite infestation. But the tolerant population still carries the genes that produce the immune response to the tapeworms.

While they havent yet tested it, Weber says it appears that these sticklebacks may have mutations to these fibrosis-associated genes that render them non-functional.

While the results are exciting for Weber, hes already looking toward future research that he hopes will further tell the genetic story of sticklebacks abundant adaptations, and by extension reveal biological processes with implications across the wide diversity of life on Earth.

Read more about the study and its findings from the University of Connecticut.

This study was supported by the Howard Hughes Medical Institute Early Career Scientist fellowship, as well as grants from the National Institutes of Health (1R01AI123659-01A1, 1R01AI146168 and 1R35GM142891).

See the article here:
How a small, unassuming fish helps reveal gene adaptations - University of Wisconsin-Madison

Anything that changes the way individuals and medical professionals view nutrition is undoubtedly going to be reflected in other areas. And an obvious one, no doubt, is the food industry. Whatever the real difference gene variations make in terms of health, the reality is this: The more that's discovered, the more reactions are going to be experienced in different ways, and on different levels.

It's already the case that foods are sold that are enriched in some way, or it's highlighted how they're rich in certain nutrients. At the same time, foods for specific diets, such as keto, to treat certain ailments are also available. As nutrigenomics advances, nutrition plans can be created for certain genetic groups (viaIndian Journal of Horticulture).

There have long been diets and food products targeted at specific health conditions keto is aimed at lowering blood sugar levels and tackling type 2 diabetes, for example (perHealthline). This is whereby a variant of one gene has led to a disorder of some kind and there's a direct connection. However, nutrigenomics is more expansive, and more complex perhaps, as it may be that a number of genetic variations impact a number of different responses to nutrition. It's when these multiple changes are combined that they create an outcome.

The result is food that's created to deal with these differences. A University of Auckland study, highlighted in aHealthy Food Guidearticle, focuses on a gene-diet factor in why Crohn's disease is higher in New Zealand, and one area in particular. The guide explains, "The research team is studying the link between foods eaten by people with Crohn's disease and different variations of the disease-related genes. Information about lifestyle and symptoms are also collected to learn more about the disease and potentially to allow tailoring of foods to genetic type."

Read the original here:
How Nutrigenomics Explores Links Between Nutrition And Genes - Health Digest