Category Archives: Human Genetics

Are women born with a maternal instinct, or is it developed? Are motherhood practices passed down genetically, or are they learned? What really makes a mom?

Abigail Tuckers latest book, Mom Genes, takes a scientific approach to these questions, but leans into her own voice. While occasionally adopting the chirpiness of a mommy blog, as one Wall Street Journal reviewer noted, Tuckers extensive research and swift storytelling provide insights into what being a mom really means.

Tuckers professional credentials as a New York Times bestselling author and a celebrated science writer help her comb through mountains of data, experiments and medical lingo to describe the how of the maternal instinct. Her book tiptoes between readable science and memoir, as her experience raising four children (alongside her husband, New York Times columnist Ross Douthat) guide her ultimate conclusion that the arrival of a newborn is rebirth for the mother, too.

In some ways, that is quite literal. Tucker explains that fetal cells remain in the mother long after childbirth, even until her death a mothers heart or brain may contain these cells from her child. But the rewiring of a mothers brain has more recognizable effects. Becoming a mother, Tucker shows, changes a woman forever.

As the world continues to shift, supporting mothers is more essential than ever. Today is a vulnerable, volatile period of maternal metamorphosis, Tucker writes, replete with inequalities in health care, education and the workforce. And COVID-19 has only piled onto it 70% of moms work (and most full time), and they bore the brunt of pandemic job losses. Which makes Tuckers writing all the more timely. Now is the time to create more adaptable support systems, but, as Tucker contends, it begins with understanding mothers and how mom genes shape their world.

This interview has been edited for length and clarity.

Deseret News: Much of your book can be summed up by one line: What feels like a mothers change of heart is actually a change of brain. How did you discover that? And what does that really mean for mothers?

Abigail Tucker: Mothers often are distracted by the physical weirdness of pregnancy and all these bizarre changes that happen to our bodies. But the most profound changes are internal. I wasnt aware that there were labs that were trying to study exactly what happens inside of a person. Once I learned that, I had to go to the labs and even volunteer for a couple of experiments to learn a little bit more about what might be happening inside of us.

The conclusion that I came to is that scientists increasingly view motherhood as a stage of human development, like a period of neuroplasticity, where your brain is primed by the chemicals of gestation and childbirth and lactation to have this set of experiences. And youre going through a period of growth and change thats unseen in human experience, outside of childhood.

Mothers are literally being reborn, and they are growing and changing. Its not like you just discard your old self you can continue on your old path, but youre not the same.

DN: You frequently discuss the maternal instinct. But its much more than just an instinct, isnt it?

AT: When we say instinct, it sometimes implies that moms know what theyre doing, or that theres some set of automatic behaviors that we upload when we become mothers. And sadly, as a mother of four, I know thats not true. Mothers often dont know what to do at all.

Because humans are distributed around the world, theres this huge diversity of behaviors. But what unites us, and what I call the maternal instinct, is this common drive a sort of core pro-baby motive a sensitization to infant cues and a willingness to respond to them, and also this feeling of reward that you get from infants.

We all have this sort of common spark inside of us, and that is the maternal instinct. And its not really something that youre necessarily born with. Its something that develops through exposures.

DN: You studied many different animals mammals, insects, aves and found different parenting patterns among all. What findings were most interesting to you?

AT: I was stunned by the power of maternal behavior even in the simplest mammals, like rodents. Lab rats and lab mice are one of the primary vehicles scientists use to study the maternal brain and the idea that its conserved across species. So by learning about rats, were not just interested in rats. Were actually learning about ourselves.

For example, if you give a rat whos not a mother a choice between food and babies, shes always going to choose the food. But if you gave the mother the same choice, her reward system has changed, and she chooses babies. So I was struck by the kinship that we have with these super simple mammal mothers.

DN: I was fascinated by what you call social support you even call it love at one point. Tell me more about why thats so important for mothers.

AT: One of the dangers about talking about maternal instinct, and one of the things Im hoping to warn against, is this idea that when mothers become mothers, they feel this attraction to and love for their babies, and that theyre somehow on autopilot.

One of the interesting things about the study of how mothers are influenced by their social world is that moms continue to be very receptive to signals that they receive from their surroundings. Those could be environmental signals. It could be stress. Even exposure to plastics and other environmental toxins can change maternal behavior. But the signals that you get from the people in your community are also really important.

The good thing about maternal behavior is that we can, as humans, control our environment. We can take steps on a national level to safeguard maternal psychology, but then also on a personal level, just like reaching out to the moms in your world. If somebody has a new baby, and you drop off dinner for her, it shows that you actually care about her and that she matters that she has a place in the social world. So, I say, bring her five dinners.

DN: You bust one motherhood myth the idea that there are certain types of mothers and every mother is just one type. In fact, you write that youve been many mothers yourself. What does that mean?

AT: There are not that many strategic advantages to having four kids. But one of the interesting things is that Ive been able to compare and contrast over the course of these four children my own parenting.

The difference between having a boy and a girl is more than just buying blue stuff or pink stuff. Theres all kinds of physiological and mental fallout from that, like how moms who have sons are subject to a little more physical stress in pregnancy, and they may be slightly more prone to postpartum depression.

The variables at play things like maternal age, if you had a C-section or really painful delivery all of these different factors are part of the stew that is you. Youre not just one person whos just going to be carrying the mom flag. You are plastic and changing and if you are one mom for your first pregnancy, four pregnancies later you may be different, in a lot of ways.

DN: You dedicate your final chapter to a path forward for mothers including legislative solutions like paid maternal leave and child tax credit reform. With nearly two dozen congresswomen in Washington with young children at home, is there momentum for this?

AT: Mothers are very good at pushing, as we all know. I do think that having more women who are mothers in elected office is one of the best things we could possibly have for maternal reform.

And thats something I want to be clear about: When I say that mothers brains change and you transform, I dont mean that you have to throw away your ambition and not run for Congress or anything like that. I do think that when you make that sacrifice, and do these important jobs, I think you are changed in some way.

The perspective that motherhood brings, and especially enriched by the science of understanding why you work like you do, is one of the best tools that we could possibly have.

While there are women in Congress, other types of moms might need space and might need to make the choice to stay at home if they want. Theres no one way and no sole path and no right answer. This is not just some check it off the bucket list thing, this motherhood stuff. Im hoping that mom lawmakers will reflect on that.

DN: Your book came out at the perfect time, with Mothers Day this weekend. What Mothers Day message do you hope moms will glean from your writing?

AT: My message is that instinct is well and good. And these impulses that we have to care for our children are incredibly powerful and conserved across mammals. But humans are lucky in that we can use knowledge, research and self-knowledge to make sense of the straits that we find ourselves in, and to kind of be not just the best moms that we can be, but the best human beings that we can be.

Moms are always pitted against each other the stay-at-homes versus the work-out-of-homes versus the work-in-homes. And, you know, all these different philosophies, the cry-it-out people and the attachment parenting people, and the homeschoolers, and the boarding schoolers. People are at each others throats a lot. And Im just really hoping that the book will help show people that we all have potential to become a lot of different selves, and that should lead to a newfound empathy for each other. We should be looking for ways to help each other, rather than to nitpick and criticize and judge.

Read more here:
Q&A: What the Mom Genes author wants you to know this Mothers Day - Deseret News

News Release

Wednesday, May 5, 2021

On World Asthma Day, the National Institutes of Health reaffirms its commitment to research to improve the lives of people with asthma. More than 25 million people in the United States have asthma, including 5.1 million children, according to the Centers for Disease Control and Prevention. This chronic lung disease can reduce quality of life, contributes to considerable emotional and financial stress, and is a major contributing factor to missed time from school and work. Severe asthma attacks can be life-threatening and may require emergency room visits and hospitalizations. Although asthma can affect anyone, some groups bear a disproportionate burden. For example, Black and Puerto Rican people are at higher risk of asthma than people of other races or ethnicities.

The National Institute of Allergy and Infectious Diseases (NIAID); the National Heart, Lung, and Blood Institute (NHLBI); and the National Institute of Environmental Health Sciences (NIEHS) are the lead NIH institutes that support and conduct asthma research. Among many other advances, these institutes recently released updated evidence-based guidelines for the diagnosis, management and treatment of asthma; helped better define the relationship between asthma and COVID-19; and improved understanding of the numerous factors that can influence asthma severity.

In December 2020, the NHLBI, with input from the National Asthma Education Prevention Program Coordinating Committee, announced the publication of updates to asthma management and treatment guidelines. The recommendations detailed in the 2020 Focused Updates to the Asthma Management Guidelines are designed to improve patient care and to support informed decision-making about clinical asthma management in six priority areas. These areas include use of inhaled corticosteroids, long-acting muscarinic antagonists, methods to reduce exposure to indoor allergen triggers, immunotherapy, fractional exhaled nitric oxide testing and bronchial thermoplasty.

As a respiratory disease, COVID-19 has created particular concern and uncertainty for people with asthma. While some evidence suggests that moderate-to-severe asthma might increase risk for severe illness from COVID-19, two independent, NIAID-supported studies suggest that people with allergic asthma are not at higher risk and identify a potential mechanism. These studies found that people with asthma and allergic diseases have reduced expression of the human gene encoding the receptor on airway cells that SARS-CoV-2, the virus that causes COVID-19, uses to enter and infect cells. Results anticipated from the NIAID-led Human Epidemiology and Response to SARS-CoV-2 (HEROS) study will clarify whether rates of SARS-CoV-2 infection differ between children who have asthma or other allergic conditions and children who do not.

In addition to respiratory infections, numerous environmental factors can influence asthma symptoms and severity. A NIEHS-funded study published last year was the first to link reduced emissions from coal-powered plants with asthma-related health benefits, including dramatic drops in asthma symptoms and hospitalizations. Another NIEHS-supported study found that children, especially boys, with elevated urine levels of bisphenol A (BPA)a chemical used in food packaging and other consumer goodshad more asthma symptoms. Additional research suggests that exposure to bisphenol F and bisphenol S, two chemicals increasingly used as BPA substitutes, is associated with asthma and hay fever.

The interplay between genetics and the environment also affects asthma susceptibility and severity. Two NIEHS studies helped clarify how an immune system protein called TLR5 may be involved in worsening asthma in response to environmental exposures. One study found that the lungs of people with a defective TLR5 generated much less inflammation after exposure to ozone than the lungs of healthy people. A companion study of people with asthma determined that participants who lacked a working TLR5 had fewer asthma symptoms upon exposure to house dust. NIAID-funded research provided additional insights into why some people develop asthma symptoms when exposed to household dust mites while others do not. In this study, scientists used cutting-edge genomics techniques to identify molecular features of T-cell subsets in people with asthma and allergy to dust mites.

The complexity of asthma and the broad range of factors that influence an individuals experience of the disease can pose challenges for managing the condition, suggesting the need for more personalized treatments. The NHLBI continues to support the Severe Asthma Research Program (SARP), a comprehensive study of adults and children with severe asthma, a debilitating form of the disease that often does not respond well to currently available medications. Findings from SARP informed the development of the NHLBIs Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network Study. PrecISE will evaluate several novel and approved treatments for asthma by targeting them to defined groups of adults and teenagers with severe, poorly controlled asthma who share similar characteristics, such as genetic factors or biomarkers. A recent NIAID-funded study identified immune system characteristics that distinguish subgroups of patients with severe asthma resistant to standard treatment, further helping to pave the way for individually tailored treatments.

NIH also remains dedicated to reducing the disproportionate burden of asthma among children living in low-income urban communities and certain minority populations. To extend the research performed previously by the NIAID-funded Inner City Asthma Consortium over several decades, NIAID recently funded a new clinical network initiative called Childhood Asthma in Urban Settings, or CAUSE. This program will investigate disease mechanisms and novel prevention and treatment strategies to mitigate the impact of asthma in disadvantaged child and adolescent populations. A recent NIH-funded study found new genetic variants linked to asthma severity in Puerto Rican children, who have high rates of asthma, that could lead to more targeted treatments in this group. The study includes genetic data from the NHLBIs TOPMed Program, which seeks to understand the genetic underpinnings of disease, including asthma.

As we reflect on the progress that has been made against asthma and the challenges that remain, NIH extends its gratitude to all who help make advances in care possiblefrom scientists and health care professionals to clinical research volunteers, advocates and educators. Together, we continue to advance our shared mission to develop and implement effective strategies for the management, treatment and prevention of this chronic lung disease.

About the National Institute of Allergy and Infectious Diseases (NIAID): NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit https://www.nhlbi.nih.gov.

About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit https://www.niehs.nih.gov/ or subscribe to a news list.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Original post:
NIH Statement on World Asthma Day 2021 | National Institutes of Health - National Institutes of Health

The Lyon laboratory focuses on the discovery of new and/or underexplored rare human diseases, such as Ogden, NAA15, TAF1 and KBG syndromes. The laboratory discovered and characterized the first genetic disease involving amino-terminal acetylation of proteins, with a missense mutation in the X-linked gene NAA10. We named this rare disease Ogden syndrome (OS) in honor of the hometown (Ogden, Utah), where the first family we identified with OS lived. The affected boys have a distinct combination of craniofacial anomalies, hypotonia, global developmental delays, cryptorchidism, cardiac anomalies, and cardiomegaly. We and others then found more than 50 families with overlapping phenotypes with additional mutations in NAA10 in this pathway; we also reported that de novo truncating or missense mutations in NAA15, encoding a binding partner for NAA10, are involved in congenital heart defects and/or neurodevelopment. Over the past few years, we have established various mouse models for OS, along with the characterization of cardiomyocytes derived from human induced pluripotent stem cell (iPSCs), as part of our long-term goal to understand the mechanistic basis of OS.

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Genetics Department Seminar Series: "Rare Human Diseases: Ogden syndrome and the amino-terminal acetylation of proteins" - Yale School of...

The new Education and Research Building, a nine-story biomedical research building at the University of Massachusetts Medical School, will support the development of therapeutics for some of the worlds most challenging diseases in a high-performance, sustainable environment.

The 350,000-sf facility will include space for 77 principal investigators and house the Medical Schools Horae Gene Therapy Center, the Departments of Neurology and Neurobiology, the Program in Molecular Medicine, a new Program in Human Genetics & Evolutionary Biology, and an FDA-compliant manufacturing facility for clinical trial therapeutics.

The project is being designed to meet ambitious sustainability goals, including achieving Net Zero Energy and LEED Gold certification and the integration of a high-performance double-skin facade and geothermal heat pumps. The interior features natural daylighting and transparency, active circulation, and large social and interaction spaces.

The project is slated to open in the fall of 2023. Shawmut Design Construction will be the projects construction manager.

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UMass Medical School's new Education and Research Building - Building Design + Construction

The National Academy of Sciences and American Academy of Arts andSciences announced their newly elected members this week, expanding their ranks by 11 and 25UC faculty, respectively.

Membership in these prestigious organizations puts one in distinguished company.

The National Academy of Sciences was established in 1863 under President Abraham Lincoln to recognize achievement in science. Along with the National Academy of Engineering and the National Academy of Medicine, members provide advice to the federal government on matters related to science, engineering and health. Its 2021 class includes 11 faculty from across five UC campuses who join an elite group of 2,461 active members (511 additional members are internationally-affiliated). This year, NAS elected 59 women among its 120 new members, representing a new record and near parity for its class.

The American Academy of Arts andSciences is an honorary society and independent research center that convenes leaders from across disciplines and professions to address significant challenges. More than 13,500 members have been elected since 1780, when it was founded by John Adams, John Hancock and others. 252 new members join the organization as part of its 2021 class, including 25UC faculty from eight campuses.

Congratulations to all of UCs newly elected members in both academies. They are:

Arturo Alvarez-Buylla, Heather and Melanie Muss Chair, department of neurological surgery, University of California, San Francisco

David Card, Class of 1950 Professor of Economics, department of economics, University of California, Berkeley

Glenn H. Fredrickson, Mitsubishi Chemical Chair in Functional Materials, department of chemical engineering, University of California, Santa Barbara

N. Louise Glass, professor and chair, department of plant and microbial biology, University of California, Berkeley

Holly A. Ingraham, Hertzstein Distinguished Investigator, professor, and associate vice chairman, department of cellular and molecular pharmacology, University of California, San Francisco

Kenneth Lange, Rosenfeld Professor of Computational Genetics, department of computational medicine and departments of human genetics and statistics, University of California, Los Angeles

Isabel P. Montaez, distinguished professor and chancellor's leadership professor, department of earth and planetary sciences, University of California, Davis

Denise J. Montell, Duggan Professor, department of molecular, cellular, and developmental biology, University of California, Santa Barbara

Geeta J. Narlikar, professor, department of biochemistry and biophysics, University of California, San Francisco

Linda Petzold, distinguished professor, department of computer science, University of California, Santa Barbara

Michael Turelli, distinguished professor and Joel Keizer Endowed Chair in Theoretical and Computational Biology, department of evolution and ecology, University of California, Davis

Thelists below present the American Academy of Arts and Sciences newest members grouped in thethirty sections,organized within five classes, in which they were elected. The academy has elected members by class and section since 1815.

Joseph Incandela, Joe and Pat Yzurdiaga Chair in Experimental Science, professor of physics, University of California, Santa Barbara

Marilyn N. Raphael, interim director of the Institute of the Environment and Sustainability and professor of geography, University of California, Los Angeles

Stefan Savage, professor of computer science and engineering, University of California, San Diego

Jodi M. Nunnari, distinguished professor and chair of the Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis

James A. Estes, professor of ecology & evolutionary biology, University of California, Santa Cruz

Tyrone B. Hayes, professor of integrative biology, University of California, Berkeley

Victoria L. Sork, director of the UCLA Mildred E. Mathias Botanical Garden and distinguished professor of ecology and evolutionary biology, University of California, Los Angeles

Geerat J. Vermeij, distinguished professor of marine ecology and paleoecology, University of California, Davis

Ananda Goldrath, professor of molecular biology, University of California, San Diego

Stephen P. Hinshaw, professor of psychology, University of California, Berkeley, and professor of psychiatry and behavioral sciences, and vice-chair for child and adolescent psychology, University of California, San Francisco

Judith Kroll, distinguished professor of language science, University of California, Irvine

Stefano DellaVigna, co-director of the Berkeley Initiative for Behavioral Economics and Finance, Daniel Koshland, Sr., distinguished professor of economics and professor of business administration, University of California, Berkeley

Robert Christopher Feenstra, director of the Center for International Data, C. Bryan Cameron Distinguished Chair in International Economics, University of California, Davis

Annette Vissing-Jrgensen, Arno A. Rayner Chair in Finance and Management and chair of the Finance Group at Berkeley Haas School of Business, University of California, Berkeley

Barbara Geddes, professor emeritus of political science, University of California, Los Angeles

Daniel N. Posner, James S. Coleman Professor of International Development in the Department of Political Science, University of California, Los Angeles

Kimberl W. Crenshaw, distinguished professor of law, Promise Institute Chair in Human Rights, UCLA School of Law

Barbara Rogoff, distinguished professor of psychology, University of California, Santa Cruz

Angela Y. Davis, distinguished professor emeritus, University of California, Santa Cruz

R. Jay Wallace, Judy Chandler Webb Distinguished Chair for Innovative Teaching and Research and professor of philosophy, University of California, Berkeley

Kelly Lytle Hernndez, director of the Ralph J. Bunche Center for African American Studies, Thomas E. Lifka Endowed Chair in History and professor of history, African American studies, and urban planning, University of California, Los Angeles

Andrs Resndez, professor of history, University of California, Davis

Terence O. Blanchard, Kenny Burrell Chair in Jazz Studies, University of California, Los Angeles

Elisabeth Le Guin, professor of musicology, University of California, Los Angeles

Rucker C. Johnson, Chancellors Professor of Public Policy in the Goldman School of Public Policy, University of California, Berkeley

Continued here:
National Academy of Sciences, American Academy of Arts and Sciences elect 36 new UC members - University of California

Introduction

DNA mutations are a major contributor to the development of diseases. Research into targeted therapies, as part of precision or personalized medicine, continues to expand and to include more mutations causing diseases.1 Two strategies for targeted therapy involving genetic mutation are gene therapy and genome editing, which have been applied to several diseases. In principle, gene therapy works by introducing DNA/RNA into the cells, removing or changing defective genes to drive the correct protein production. Genome editing in particular, which is one of the gene therapy techniques, is to remove, to disrupt or to correct faulty elements of DNA within the gene and leads to change sequence of the gene.2 Up to now, the approved gene therapies do not alter the genomic sequences, for instance Zynteglo for -thalassemia,3 Luxturna for Leber congenital amaurosis or retinitis pigmentosa4 and Zolgensma for spinal muscular atrophy,5 whilst the genome editing approach is still under clinical trials such as for lung cancer6 and blood disorder.7

Genome editing has become a rising star since the investigation of CRISPR/Cas9 found a defensive system from phage in bacteria.8,9 Currently, editing diseases caused by mutations and introducing the correct donor template have become much simpler and more affordable. Several components are required for CRISPR/Cas9 gene editing, including a gRNA designed to target a particular PAM sequence, the Cas9 enzyme to cut DNA and potentially a donor template.10 CRISPR/Cas9 recognizes a specific sequence, creates a double-strand break on the DNA and the cell automatically performs DNA repair, constituting an effective tool for genome editing.

CRISPR/Cas9 has been widely used for its simplicity and affordability.11 In fact, in 2020, CRISPR/Cas9 technology was awarded the Nobel Prize for its broad possible applications, simple handling and affordable price. However, low efficiency and off-targeting remain a concern in its application.10,12,13 Since the discovery of CRISPR/Cas9, many studies have been performed in vitro in human cells and in vivo in a range of animal models to correct disease-caused mutations and to create mutations for gene inactivation.13,14 Mostly, this powerful method has been applied to somatic cells, but concerns have been expressed by scientists regarding its application to germline cells that allows inheritance of the edited gene.15 Unfortunately, a red alert was raised in 2018 when one group of Chinese scientists announced the birth of twin babies for whom the CCR5 gene had been edited. Inactivation of this gene made the babies resistant to HIV invasion.16,17 Moreover, ethical concerns has been raised on the application of this technology to enhance human ability such as memory or intelligence.18

Despite the controversies, medical doctors and students need to understand the latest technology, which could potentially affect their future practice since this technology rapidly develops toward its clinical application.19 Acceptance and attitude of general public, medical doctors and students on gene therapy and genome editing have been extensively investigated and reviewed, with acceptance of this technology being affected by the education, religion, gender, age, economic status and trust to the scientist and government.20 Respondents with medical background are more likely to accept genome editing than are the general public.21 Moreover, due to the CCR5 babies scandal, public awareness of genome editing technology application, risk, safety and ethical problems increased, while the acceptance of this technology reduced.22 In Indonesia, genome editing is not part of a focus in Indonesian medical education,23 and as it is a country with a big religious population, the controversy regarding the ethics of some health approaches is unavoidable.24 Therefore, we conducted this study to explore the attitudes of Indonesian medical doctors and students toward human genome editing and the sociodemographic factors that might affect their attitude.

This cross-sectional study was part of a gene therapy and genome editing study in Indonesia which was conducted from May to December 2020, and ethics approval was obtained from the Faculty of Medicine, Universitas Airlangga No. 156/EC/KEPK/FKUA/2020. Before the start of the questionnaire, a page explaining the aim and content of the survey was provided, and informed consent, including for publication of anonymized responses, was obtained if the respondent clicked the BEGIN button to start the survey.

Primary data were collected from online questionnaires distributed through the researchers network, email and social media of medical doctors and students. Research staff shared and guided the respondents to access the online questionnaire, and the respondents completed and submitted the questionnaires independently. Respondents of this study comprised only Indonesian medical doctors and medical students, over 18 years of age, that were Indonesian citizens and who had studied in a medical program or graduated from an Indonesian Medical Faculty. Fifteen respondents were then contacted based on their answers to the online questionnaire; among these, only 10 respondents replied, and an in-depth email interview was performed by SNI, DS and AdA.25

The attitudes of respondents to genome editing were measured using a set of questionnaires. The questionnaire consisted of two sections, which comprised basic information of respondents and questions regarding their attitudes on genome editing. The questionnaire was adapted and translated by two native Indonesians from A Global Social Media Survey of Attitudes to Human Genome Editing.26 The translated questionnaire was further piloted among 20 Indonesian medical doctors to ensure the understanding of the respondents. The survey was divided into seven sections: (1) respondents characteristics (gender, age, place of residence, marital status, childbearing, education, work experience, religion and experience abroad); (2) general attitudes toward genome editing; (3) attitudes toward genome editing in somatic cells for fatal and debilitating diseases; (4) attitudes toward genome editing in embryos for fatal and debilitating diseases; (5) attitudes toward genome editing in the embryo to change individual characteristics, such as physical, intelligence quotient (IQ) and strength; (6) factors affecting the attitudes toward genome editing; and (7) their agreement in genome editing implementation in Indonesia. Finally, respondents were asked to answer an open-ended question regarding their concerns toward genome editing. The in-depth interview questions were developed based on each respondents answer, focusing on their concerns on genome editing.

Respondents were divided into two groups: doctors and students. The religion, place of residence and economic status were simplified into two categories each, ie, majority and minority; inside or outside the main islands; and lower and higher economic status, respectively. The attitudes toward genome editing in somatic cells and in embryos as well as its application in Indonesia were measured using a 5-point Likert scale, rated from strongly disagree to strongly agree, which was aggregated to disagree, neutral and agree, while attitudes toward genome editing in embryos to change individual characteristics were measured using yes/no answers. Additionally, participants chose from a list the factors that affected their attitudes toward genome editing, and the number of respondents per factor was calculated and divided by the total respondents; respondents could also write in their concerns regarding genome editing technology.

Data were processed using Microsoft Excel and analyzed using SPSS 25.0 (IBM, Chicago, IL, USA), and graphs were visualized using GraphPad Prism version 5.00 (La Jolla, California, USA). Descriptive statistical analyses were performed, and response rates were calculated as percentages on every item related to categorical variables. Differences between groups were measured using the t-test or MannWhitney U and KruskalWallis H-test to determine the sociodemographic factors influencing the respondents attitudes toward genome editing; significance was defined as a p-value < 0.05. The effect size further performed to measure the strength of the differences between two groups, with the interpretations for effect size g being: g=0.20 as small, g=0.5 as medium and g=0.8 as large, following the criteria proposed by Hedges (1985).27,28

Of the 1076 responses received, 1055 questionnaires were valid and used in the final analysis, corresponding to an effective rate of 98.05%. Four returned responses were excluded because they were incomplete, and 17 responses were excluded due to unmet the eligibility criteria. The ratio between doctors and students was almost 1:1, with females as the majority. A discrepancy of age was observed between the two groups: all the respondents in the student group were between 18 and 30 years old, while young doctors (18 to 40 years old) were the majority in the medical doctor group. As expected, the majority of respondents were located in Java and Bali, which are the most developed provinces in Indonesia and have more doctors and medical schools compared with other provinces. Moreover, as Indonesia is a Muslim majority country, two-thirds of the respondents in each group were Muslim. Based on their self-proclaimed economic status, the majority of respondents in the two groups had lower economic status. As expected, the education between the two groups differed; only 35.8% of the medical doctors pursued specialization/post-graduate studies. However, no significant difference was found between doctor and student respondents participating in mobility programs in other countries (20% vs 15.9%, respectively). The difference between the two groups also could be observed concerning their work experience. The majority of doctors had more than 5 years of working in their field, while the majority of students still studied in their fifth year. Nearly all respondents in the student group were unmarried and without children, while two-thirds of respondents in the doctor group were married and with children. Characteristics of the respondents are summarized in Table 1.

Table 1 Characteristics of Respondents

Fifteen questions assessed attitudes toward genome editing applications in humans (Table S1). The results showed very low familiarity with genome editing in the doctor and student groups (12.2% and 13.1%, respectively) even though more of the respondents had heard of this technology (21.3% and 28%, respectively, Figure 1A). The respondents were more familiar with genetically modified food (27.1% and 20.4%, respectively) or at least had heard of this issue (38.8% and 28.2%, respectively, Figure 1B). Despite genome editing technology being in the spotlight in these past 3 years with the CCR5 edited babies scandal and Nobel Prize winners, the respondents' knowledge was significantly lower compared with GMO and the more common issues in gene technology which have attracted more media coverage (p < 0.01). This was an unexpected finding, because medical doctors' and students' knowledge on this technology was lower than the US publics knowledge (31%).29

Figure 1 Knowledges and attitudes of Indonesian medical doctorsand medical studentstoward genome editing. (A) Knowledge on genome editing . (B) Knowledge on genetically modified food. The knowledge was divided into never heard, ever heard but not familiar and know which meansthe respondents were familiar with the technology including superficial knowledge to deep knowledge. (C) Attitudes of all respondents on GM food and genome editing application in health and non-health-relatedmatter, including application in Indonesia.

Although respondents had little knowledge of this field, no specialty terms were used in the questionnaire, allowing them to complete the survey. The majority of respondents (60.76%) supported the application of genome editing as therapy for fatal diseases in somatic cells, which prohibits inheritance in the next generation. Regarding its application in alleviating the burden of debilitating diseases in somatic cells, an almost similar number was obtained: 61.33% supported this aim. The respondents in the doctor group were more likely to support the applications in somatic cells for fatal and debilitating diseases compared to the student group (p = 0.000 and p = 0.000, respectively). Meanwhile, the support for the application of this technology in the embryo stage was not significantly different between the two groups (Table 2). However, the values of effect size g were 0.22 for both questions or had small effect, although the results were statistically significant.

Table 2 Knowledge and Attitude Toward Genome Editing Application

Overall, the number of respondents who agreed was slightly reduced when the application was to embryos, meaning the edited gene could be inherited by the next generation, both for fatal and debilitating diseases. Interestingly, their support of genome editing application concerning the embryo was higher compared with the application for genetically modified food (28.25%, Figure 1C). This might be caused by a lower acceptance of genetically modified food in this study compared with other studies (3057%).30,31 Nevertheless, similar to other countries, the support for human enhancement at the embryo stage was lower than that for treatment of health-related matters, with only 26.07% respondents. Moreover, the majority of respondents did not have any view or were neutral regarding the use of genome editing in Indonesia (Figure 1C).

We further explored the respondents' preference regarding enhancing individual characteristics at the embryonic stage. If the technology was safe, the respondents prefer to enhance the intelligence (40.53%) compared to sport ability/strength (28.69%) and physical appearance (17.52%). Factors of concern regarding genome editing included the possibility of inheritance (14.19%), expense (21.93%), side effects (22.24%), violation of privacy (9.5%), violation of fate (15.37%), violation of religious values (15.71%) and others such as misconduct, lack of evidence and less expertise (1.07%) (Table S2 C1-C5).

To determine the sociodemographic factors affecting the respondents' attitudes on genome editing, MannWhitney U and KruskalWallis H-test were performed. Our study supported that males were more likely to support genome editing application at somatic cells (p = 0.000) and embryo stages, both for health (p = 0.004) and non-health (p = 0.001) related matter, including its application in Indonesia (p = 0.000), similar with other studies (Table 3). This trend might be caused by males tending to follow the logic, while females tend to accept and find a supporting reason (Table S2, C6 and C7).

Table 3 Influence of Sociodemographic Factors on Respondents Attitudes

Age was also a contributing factor affecting Indonesian medical doctors attitude toward genome editing technology. The older respondents were more likely to support genome editing at somatic cells for treating fatal diseases (p = 0.049), and respondents aged 1830 years and >50 years were more likely to support the human enhancement ability (p = 0.003). Moreover, respondents residing outside of the main islands were more likely to support the latter application (p = 0.028); however, respondents from the main islands were more likely to support the application of this technology in Indonesia (p = 0.014) (Table 3). In the main island, the developments, the facilities and the transfer of knowledge can be performed more easily than in the outer parts of Indonesia.

Religion greatly influenced respondents' attitudes because the respondents with the majority religious affiliation in Indonesia were less permissive concerning applying genome editing application to treat fatal diseases (p = 0.016), debilitating diseases (p = 0.000) and human enhancement (p = 0.012), whether it could or could not be inherited to the next generation (Table 3, S2 C8 and C9). Moreover, they also were more likely to oppose its application in Indonesia (p = 0.001) when compared with other religions.

Respondents with higher education levels were more likely to support the application at somatic cells for fatal (p = 0.000) and debilitating diseases (p = 0.001) but tended to oppose this technology application when used to enhance human ability or performance (p = 0.001). This might relate to the ease of access to new information, such as journals, seminars and exchange/internship to developed countries (Table S2 C5 and C6). The exposure to broader society was also associated with respondents being more permissive on implementation in Indonesia (p = 0.014); however, this exposure did not significantly influence their view on genome editing technology in health and non-health-related matter.

Moreover, in line with other studies, respondents with higher self-proclaimed economic status were more likely to support the use of this technology on somatic cells for fatal and debilitating diseases (p = 0.005 and p = 0.003), implying that the changes were unable to be inherited in the next generation (Table S2).

To our knowledge, this constitutes the first study to measure Indonesian medical doctors' and students' attitudes toward genome editing. Our study found that the knowledge of Indonesian medical doctors and medical students on genome editing was lower compared to similar studies in various countries.22,26 Moreover, 60.76% of respondents agreed with the application of genome editing in somatic cells and embryos to improve health conditions. This acceptance reduced to only a quarter when applied to non-health-related aspects. This finding is similar to the public acceptance rate in the United States, where approximately 64% of the respondents accepted genome editing to cure diseases, while only 33% respondents accepted its application in enhancing human ability.32 Moreover, a study of 1004 Australians demonstrated a similar conclusion.33 This finding slightly differs with a study of geneticists in US, in which the majority support the use of genome editing on somatic cells and for research purposes, but not in embryos/germline cells.34

As reviewed by Delhove et al, sociodemographic factors influenced the acceptance by the general public toward gene therapy and genome editing.20 Our study found that gender, age, economic status, religion, education and place of residence influenced the attitude of the respondents on genome editing technology. Similar to the findings of a study conducted in the US on 1600 adult citizens,32 a study on 12,000 persons of the general public (mainly the US, UK and China),26 a study on 1004 Australians33 and 12,716 persons of the general public of 10 European countries and US citizens, our study found that males were more likely to approve genome editing application, both for disease treatment and human enhancement ability, and its application in Indonesia. This finding differs from that of a study in 13,201 Chinese persons of the general public, with 2165 clinicians, that concluded that females were more likely to accept the application of gene therapy for genetic disease treatments, including genome alterations approach.21

A relationship between age and the attitude on genome editing has been shown in many studies. Some studies reported that older respondents were less permissive regarding the usage of genome editing,22,33,35 especially on non-health-related matters.26 However, a study on 10 European countries and US citizens found no significant contribution of age on the application at the somatic cells or the embryos.36 In contrast with other studies, here we demonstrated that older respondents were more supportive of genome editing applications to treat fatal diseases at the somatic cells. Additionally, respondents less than 30 years old and more than 50 years old were more likely to permit the usage on non-health-related matters.

Moreover, economic status also might contribute to respondents acceptance of this technology, especially on its application to the somatic cells. This result was similar to a study from Australia that found the respondents from a country with high economic levels/GDP more likely to accept the implementation of genome editing26 and a study from US that showed respondents with higher family income more likely to support the human genome editing technology.32 This also might be related with the place of residence, as our study found that respondents who resided at more developed islands were more likely to support the application of genome editing technology in Indonesia, while respondents who resided at less developed islands were more likely to support this technology for enhancing human ability which might bring more benefit. A study in Europe suggested that less support from the lower-income respondents and less developed countries might relate to the lower benefit that they will get from this technology and to trust issues with the regulation and the government.37

Another factor that might influence the attitude toward genome editing is religion. As a country with a Muslim majority population, religious value is embedded in many aspects, including the medical field. Our study found that the minority were more likely to agree to its use in health and non-health-related matters, including its application in Indonesia. It was in line with studies in religious individuals who consistently rejected changes to the genome because they conflicted with religious teachings.26,37 It might also be related with less trust of the scientific community to guide this technology in a responsible way.32 However, a study in the general public, university students and high school teachers from various countries in Asia, Australia, New Zealand, Russia and China found no significant effect of religion on the application of gene therapy that included gene correction.38,39

Education was one of the influencing factors on the attitudes of the respondents to this rising technology. Our study found that respondents with higher education had more favorable attitude toward genome editing as treatment for fatal and debilitating diseases on somatic cells, but they were more likely to oppose its application for increasing human ability. Moreover, education did not affect the respondents attitude toward genome editing application on the embryo, both for fatal and debilitating diseases. A study by McCaughey showed that respondents with tertiary education were more likely to support this technology application as treatment for a fatal or life-threatening condition, either on somatic cells or embryo stage; in addition, they were also more likely to support their usage to prevents debilitating diseases at the embryonic stage, indicating that the edited gene was inheritable to the next generation.26 Similar with our results, studies in Australian, European and US citizens found no significant association between education and prenatal application of this technology.33,36 Nevertheless, even though those with experience abroad had increased knowledge regarding genome editing and the CCR5 edited infants, their views of its application did not differ from the respondents who did not have any experience in other countries. Respondents with experience abroad were also more likely to support the implementation of this technology in Indonesia.

Furthermore, even though the cost of CRISPR/Cas is lower than other genome editing technology, Indonesian medical doctors and students still emphasized the high costs that might become a burden on the application, and same reason applies to the reluctance to do genetic testing.40 Major side effects or safety of this technology were also a concern, as this technology is still in the development stage, with lack of supportive evidence, and less expertise in the Indonesian medical field. Increasing attention is also given by the Japanese general public, especially after the announcement of twins born with the edited CCR5 gene, mostly regarding the safety and ethical issues.22

Unfortunately, even though this technology raised controversial issues in 2018 and received the Nobel Prize in 2020, the majority of Indonesian medical doctors were still unaware of this issue. This implied that more effort was needed to broaden the knowledge of Indonesian medical doctors regarding this new technology approach, so that they will be more aware of and prepared for the upcoming treatment technologies. Consultation to the public before its application is necessary before implementation in Indonesia to avoid public negative sentiment and rejection.

We recognized the limitation of our study was the utilization of an online questionnaire; thus, there is a possibility for bias since respondents unfamiliar with the internet or residing in remote areas were unable to access the questionnaire. However, the sociodemographic distribution of our respondents was in line with that of Indonesian citizens. Moreover, without face-to-face interaction, lower engagement with the question might affect the results obtained in this study.

This study revealed that even though the majority of Indonesian medical doctors and students were unfamiliar with genome editing, they agreed with the use of genome editing to treat fatal and debilitating diseases, but fewer agreed with applying the method to improve non-health-related aspects. However, some concerns remain regarding the safety, misuse, ethics, religious values and cost of this treatment in Indonesia. Expanding the horizons and increasing the awareness of Indonesian medical doctors and students regarding new technologies that might affect the future of the medical field and humankind are important.

We would like to thank Dr. Zakiyatul Faizah, MD for valuable comments and suggestions.

This study was funded by RKAT Faculty of Medicine Universitas Airlangga as Rector's Decree No. 346/UN3/2020.

The authors report no conflicts of interest in this work.

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Genome editing attitudes of medical students and doctors | JMDH - Dove Medical Press

Six Faculty: Election to American Academy of Arts & Sciences

Six members of the University of Pennsylvania faculty have been elected to the American Academy of Arts & Sciences. They join more than 250 new members honored in 2021, recognized for their work to help solve the worlds most urgent challenges, create meaning through art, and contribute to the common good.

Cristina Bicchieri is the S. J. Patterson Harvie Professor of Social Thought and Comparative Ethics in the School of Arts & Sciences. She is also a professor of legal studies at the Wharton School. She is the director of the Center for Social Norms & Behavioral Dynamics and founding director of the Master of Behavioral and Decision Sciences program. Her research sits at the intersection of philosophy, game theory, and psychology, with a primary research focus on judgment and decision-making, as well as on how expectations affect behavior. Dr. Bicchieris work also examines the nature and evolution of social norms, how to measure them, and what strategies are necessary to foster social change.

Michael Hanchard is the Gustav C. Kuemmerle Professor of Africana Studies and professor of political science in the School of Arts & Sciences. He also serves as director of the Marginalized Populations Project, a collaborative research initiative designed to explore political dynamics between populations with unequal, minimal, or non-existent state protections and national governments. His research and teaching interests combine a specialization in comparative politics with an interest in contemporary political theory, encompassing themes of nationalism, racism, xenophobia, and citizenship.

Vijay Kumar is the Nemirovsky Family Dean of Penn Engineering with appointments in the departments of mechanical engineering & applied mechanics, computer & information science, and electrical & systems engineering. He is an internationally recognized robotics expert who specializes in multi-agent systems, teams of robots that can cooperate to complete a task. Dr. Kumars research on new ways for these teams to sense their environments and communicate will help them collaborate on tasks that no single robot could do on its own, whether splitting up to count oranges in an orchard or coming together to lift a heavy payload.

Stanley Plotkin is an emeritus professor of pediatrics and microbiology at the Perelman School of Medicine, an emeritus professor of virology at the Wistar Institute, and former director of infectious diseases at the Childrens Hospital of Philadelphia (CHOP). Dr. Plotkin has spent his career focused on developing vaccines for diseases like rubella, polio, rabies, varicella, and cytomegalovirus. He is also a founding member of the Pediatric Infectious Diseases Society.

Sarah Tishkoff is the David and Lyn Silfen University Professor in Genetics and Biology, holding appointments in the Perelman School of Medicine and School of Arts & Sciences. She is also director of the Penn Center for Global Genomics and Health Equity. Dr. Tishkoff studies human genetic diversity, specifically that of African populations, blending field, lab, and computational approaches. Her work has not only elucidated African population history but also how genetic variation affects traits such as disease susceptibility or ability to metabolize drugs.

Kenneth Zaret is the Joseph Leidy Professor in the department of cell and developmental biology at the Perelman School of Medicine. He is also the director of Penns Institute for Regenerative Medicine (IRM). Dr. Zaret joined Penn in 2009 as associate director of IRM and co-director of the epigenetics program, where he served until 2014. He is also a member of the Cell and Molecular Biology Graduate Group. The Zaret Lab focuses on understanding how genes are regulated to allow one type of cell to change into another type, cell type control that occurs in embryonic development and tissue regeneration.

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Six Faculty: Election to American Academy of Arts & Sciences - UPENN Almanac

New DNA sequencing technologies and assembly methods let researchers read the entire genomes of 25 species: pale spear-nosed bat, greater horseshoe bat, Egyptian fruit bat, greater mouse-eared bat, Kuhls pipistrelle bat, velvety free-tailed bat, Canada lynx, marmoset, vaquita, platypus, echidna, zebra finch, kkp, Annas hummingbird, domestic duck, emu, Goodes thornscrub tortoise, two-lined caecilian, zig-zag eel, climbing perch, flier cichlid, eastern happy cichlid, channel bull blenny, blunt-snouted clingfish, and thorny skate. The animals span all major classes of vertebrates. Credit: Irving Geis/HHMI

A bold project to read the complete genetic sequences of every known vertebrate species reaches its first milestone by publishing new methods and the first 25 high-quality genomes.

Its one of the most audacious projects in biology today reading the entire genome of every bird, mammal, lizard, fish, and all other creatures with backbones.

And now comes the first major payoff from the Vertebrate Genomes Project (VGP): near complete, high-quality genomes of 25 species, Howard Hughes Medical Institute (HHMI) Investigator Erich Jarvis with scores of coauthors report April 28, 2021, in the journal Nature. These species include the greater horseshoe bat, the Canada lynx, the platypus, and the kkp parrot one of the first high-quality genomes of an endangered vertebrate species.

The paper also lays out the technical advances that let scientists achieve a new level of accuracy and completeness and paves the way for decoding the genomes of the roughly 70,000 vertebrate species living today, says HHMI Investigator and study coauthor David Haussler, a computational geneticist at the University of California, Santa Cruz (UCSC). We will get a spectacular picture of how nature actually filled out all the ecosystems with this unbelievably diverse array of animals.

Together with a slew of accompanying papers, the work is beginning to deliver on that promise. The project team has discovered previously unknown chromosomes in the zebra finch genome, for example, and a surprise finding about genetic differences between marmoset and human brains. The new research also offers hope for saving the kkp and the endangered vaquita dolphin from extinction.

These 25 genomes represent a key milestone, explains Jarvis, VGP chair and a neurogeneticist at The Rockefeller University. We are learning a lot more than we expected, he says. The work is a proof of principle for whats to come.

The marmoset genome reveals that several brain genes have pathogenic differences to those in humans. The finding highlights why its important for scientists to consider genomic context when developing animal models.

The VGP milestone has been years in the making. The projects origins date back to the late-2000s, when Haussler, geneticist Stephen OBrien, and Oliver Ryder, director of conservation genetics at the San Diego Zoo, figured it was time to think big.

Instead of sequencing just a few species, such as humans and model organisms like fruit flies, why not read the complete genomes of ten thousand animals in a bold Genome 10K effort? At the time, though, the price tag was hundreds of millions of dollars, and the plan never really got off the ground. Everyone knew it was a great idea, but nobody wanted to pay for it, recalls HHMI Investigator and HHMI Professor Beth Shapiro, an evolutionary biologist at UCSC and a coauthor of the Nature paper.

Plus, scientists early efforts at spelling out, or sequencing, all the DNA letters in an animals genome were riddled with errors. In the original approach used to complete the first rough human genome in 2003, scientists chopped up DNA into short pieces a few hundred letters long and read those letters. Then came the fiendishly difficult job of assembling the fragments in the right order. The methods werent up to task, resulting in misassemblies, major gaps, and other mistakes. Often it wasnt even possible to map genes to individual chromosomes.

Canada Lynx (lynx canadensis) in Winter.

The introduction of new sequencing technologies with shorter reads helped make the idea of reading thousands of genomes possible.These rapidly developing technologies slashed costs but also reduced quality in genome assembly structure. Then in 2015, Haussler and colleagues brought in Jarvis, a pioneer in deciphering the intricate neural circuits that let birds trill new tunes after listening to others songs. Jarvis had already shown a knack for managing big, complex efforts. In 2014, he and more than a hundred colleagues sequenced the genomes of 48 bird species, which turned up new genes involved in vocal learning. David and others asked me to take on leadership of the Genome 10K project, Jarvis recalls. They felt I had the personality for it. Or, as Shapiro puts it: Erich is a very pushy leader, in a nice way. What he wants to happen, he will make happen.

Jarvis expanded and rebranded the Genome 10K idea to include all vertebrate genomes. He also helped launch a new sequencing center at Rockefeller that, together with one at the Max Planck Institute in Germany led by former HHMI Janelia Research Campus Group Leader Gene Myers, and another at the Sanger Institute in the UK led by Richard Durbin and Mark Blaxter, is currently producing most of the VGP genome data. He asked Adam Phillippy, a leading genome expert at the National Human Genome Research Institute (NHGRI), to chair the VGP assembly team. Then, he found about 60 top scientists willing to use their own grant money to pay for the sequencing costs at the centers to tackle the genomes they were most interested in. The team also negotiated with the Mori in New Zealand and officials in Mexico to get kkp and vaquita samples in a beautiful example of international collaboration, says Sadye Paez, program director of the VGP at Rockefeller.

The massive team of researchers pulled off a series of technological advances. The new sequencing machines let them read DNA chunks 10,000 or more letters long, instead of just a few hundred. The researchers also devised clever methods for assembling those segments into individual chromosomes. They have been able to tease out which genes were inherited from the mother and the father. This solves a particularly thorny problem known as false duplication, where scientists mistakenly label maternal and paternal copies of the same gene as two separate sister genes.

I think this work opens a set of really important doors, since the technical aspects of assembly have been the bottleneck for sequencing genomes in the past, says Jenny Tung, a geneticist at Duke University, who was not directly involved with the research. Having high-quality sequencing data will transform the types of question that people can ask, she says.

The teams improved accuracy shows that previous genome sequences are seriously incomplete. In the zebra finch, for example, the team found eight new chromosomes and about 900 genes that had been thought to be missing. Previously unknown chromosomes popped up in the platypus as well, as members of the team reported online in Nature earlier this year. The researchers also plowed through, and correctly assembled, long stretches of repetitive DNA, much of which contain just two of the four genetic letters. Some scientists considered these stretches to be non-functional junk or dark matter. Wrong. Many of the repeats occur in regions of the genome that code for proteins, says Jarvis, suggesting that the DNA plays a surprisingly crucial role in turning genes on or off.

Thats just the start of what the Nature paper envisions as a new era of discovery across the life sciences. With every new genome sequence, Jarvis and his collaborators uncover new and often unexpected findings. Jarviss lab, for example, has finally nabbed the regulatory region of a key gene parrots and songbirds need to learn tunes; next, his team will try to figure out how it works. The marmoset genome yielded several surprises. While marmoset and human brain genes are largely conserved, the marmoset has several genes for human pathogenic amino acids. That highlights the need to consider genomic context when developing animal models, the team reports in a companion paper in Nature. And in findings published last year in Nature, a group led by Professor Emma Teeling at University College Dublin in Ireland discovered that some bats have lost immunity-related genes, which could help explain their ability to tolerate viruses like SARS-CoV-2, which causes COVID-19.

The highly endangered kkp parrot lacks genetic diversity but has apparently been able to purge deleterious mutations, a new analysis of its genome suggests.

The new information also may boost efforts to save rare species. It is a critically important moral duty to help species that are going extinct, Jarvis says. Thats why the team collected samples from a kkp named Jane, part of a captive breeding program that has brought the parrot back from the brink of extinction. In a paper published in the new journal Cell Genomics, of the Cell family of journals, Nicolas Dussex at the University of Otago and colleagues described their studies of Janes genes along with other individuals. The work revealed that the last surviving kkp population, isolated on an island off New Zealand for the last 10,000 years, has somehow purged deleterious mutations, despite the species low genetic diversity. A similar finding was seen for the vaquita, with an estimated 10-20 individuals left on the planet, in a study published in Molecular Ecology Resources, led by Phil Morin at the National Oceanic and Atmospheric Administration Fisheries in La Jolla, California. That means there is hope for conserving the species, Jarvis concludes.

High-quality gene sequences show previously unknown chromosomes in the platypus.

The VGP is now focused on sequencing even more species. The project teams next goal is finishing 260 genomes, representing all vertebrate orders, and then snaring enough funding to tackle thousands more, representing all families. That work wont be easy, and it will inevitably bring new technical and logistical challenges, Tung says. Once hundreds or even thousands of animals readily found in zoos or labs have been sequenced, scientists may face ethical hurdles obtaining samples from other species, especially when the animals are rare or endangered.

But with the new paper, the path ahead looks clearer than it has in years. The VGP model is even inspiring other large sequencing efforts, including the Earth Biogenome Project, which aims to decode the genomes of all eukaryotic species within 10 years. Perhaps for the first time, it seems possible to realize the dream that Haussler and many others share of reading every letter of every organisms genome. Darwin saw the enormous diversity of life on Earth as endless forms most beautiful, Haussler observes. Now, we have an incredible opportunity to see how those forms came about.

Reference: Towards complete and error-free genome assemblies of all vertebrate species by Arang Rhie, Shane A. McCarthy, Olivier Fedrigo, Joana Damas, Giulio Formenti, Sergey Koren, Marcela Uliano-Silva, William Chow, Arkarachai Fungtammasan, Juwan Kim, Chul Lee, Byung June Ko, Mark Chaisson, Gregory L. Gedman, Lindsey J. Cantin, Francoise Thibaud-Nissen, Leanne Haggerty, Iliana Bista, Michelle Smith, Bettina Haase, Jacquelyn Mountcastle, Sylke Winkler, Sadye Paez, Jason Howard, Sonja C. Vernes, Tanya M. Lama, Frank Grutzner, Wesley C. Warren, Christopher N. Balakrishnan, Dave Burt, Julia M. George, Matthew T. Biegler, David Iorns, Andrew Digby, Daryl Eason, Bruce Robertson, Taylor Edwards, Mark Wilkinson, George Turner, Axel Meyer, Andreas F. Kautt, Paolo Franchini, H. William Detrich III, Hannes Svardal, Maximilian Wagner, Gavin J. P. Naylor, Martin Pippel, Milan Malinsky, Mark Mooney, Maria Simbirsky, Brett T. Hannigan, Trevor Pesout, Marlys Houck, Ann Misuraca, Sarah B. Kingan, Richard Hall, Zev Kronenberg, Ivan Sovi, Christopher Dunn, Zemin Ning, Alex Hastie, Joyce Lee, Siddarth Selvaraj, Richard E. Green, Nicholas H. Putnam, Ivo Gut, Jay Ghurye, Erik Garrison, Ying Sims, Joanna Collins, Sarah Pelan, James Torrance, Alan Tracey, Jonathan Wood, Robel E. Dagnew, Dengfeng Guan, Sarah E. London, David F. Clayton, Claudio V. Mello, Samantha R. Friedrich, Peter V. Lovell, Ekaterina Osipova, Farooq O. Al-Ajli, Simona Secomandi, Heebal Kim, Constantina Theofanopoulou, Michael Hiller, Yang Zhou, Robert S. Harris, Kateryna D. Makova, Paul Medvedev, Jinna Hoffman, Patrick Masterson, Karen Clark, Fergal Martin, Kevin Howe, Paul Flicek, Brian P. Walenz, Woori Kwak, Hiram Clawson, Mark Diekhans, Luis Nassar, Benedict Paten, Robert H. S. Kraus, Andrew J. Crawford, M. Thomas P. Gilbert, Guojie Zhang, Byrappa Venkatesh, Robert W. Murphy, Klaus-Peter Koepfli, Beth Shapiro, Warren E. Johnson, Federica Di Palma, Tomas Marques-Bonet, Emma C. Teeling, Tandy Warnow, Jennifer Marshall Graves, Oliver A. Ryder, David Haussler, Stephen J. OBrien, Jonas Korlach, Harris A. Lewin, Kerstin Howe, Eugene W. Myers, Richard Durbin, Adam M. Phillippy and Erich D. Jarvis, 28 April 2021, Nature.DOI: 10.1038/s41586-021-03451-0

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First Major Discoveries Reported From Project to Read Complete Genetic Sequences of All 70,000 Vertebrate Species - SciTechDaily

Early in human development, during the first trimester of gestation, a fetus may have XX or XY chromosomes that indicate its sex. Yet at this stage a mass of cells known as the bipotential gonad that ultimately develops into either ovaries or testes has yet to commit to its final destiny.

While researchers had studied the steps that go into the later stages of this process, little has been known about the precursors of the bipotential gonad. In a new study published in Cell Reports and co-led by Kotaro Sasaki of Penns School of Veterinary Medicine, an international team lays out the detailed development of this key facet of sexual determination in two mammalian models.

Using single-cell transcriptome data, we can get a lot of information about gene expression at each developmental stage, says Sasaki. We can define what the default process is and how it might go awry in some cases. This has never been done in traditional developmental biology. Now we can understand development in molecular terms.

Disorders of sex development (DSD) occur when internal and external reproductive structures develop differently from what would be expected based on an individuals genetics. For example someone with XY chromosomes might develop ovaries. These conditions often affect fertility and are associated with an increased risk of germ cell tumors.

These disorders oftentimes create psychological and physical distress for patients, Sasaki says. Thats why understanding gonadal development is important.

To understand atypical development, Sasaki and colleagues in the current study sought to layout the steps of typical development, working with a mouse model and a monkey model.

The researchers began by examining mouse embryos throughout embryonic development, using molecular markers to track the location of different proteins suspected to be involved in the formation of reproductive structures. They noticed that by day nine of a mouses embryonic development, a structure called the posterior intermediate mesoderm (PIM) lit up brightly with the marker for a gene critical to the development of gonads, kidneys, and the hormone-producing adrenal glands, which are located adjacent to the kidneys.

Zeroing in on the PIM and its progeny cells, the team found that, by day 10.5, these also expressed a marker known to be associated with the bipotential gonad.

People have previously studied the origin of the urogenital organs and the kidney and based on that believed that their origins were very close, Sasaki says. So our hypothesis was that the PIM was the origin of the gonads as well as the kidneys.

To identify the origin of the gonad, they performed lineage tracing, in which scientists label cells in order to track their descendents, which indeed supported the connection between the PIM and the gonads.

To further confirm that the PIM played a similar role in an organism closer to humans in reproductive biology, the researchers made similar observations in embryos from cynomolgus monkeys. Though the developmental timing was different from the mouse, as was expected, the PIM again appeared to give rise to the bipotential gonad.

Digging even deeper into the molecular mechanism of the transition between the PIM and bipotential gonad, the researchers used a cutting-edge technique: single-cell sequencing analysis, whereby they can identify which genes are being turned on during each developmental stage.

Not only were they able to identify genes that were turned onmany of which had never before been associated with reproductive developmentbut they observed a transition state between the PIM and bipotential gonad, called the coelomic epithelium. Comparing the mice and monkey embryos, the researchers came up with a group of genes that were conserved, or shared between the species. Some of these genes are already known to be important for the development of mouse and human ovaries and testes, Sasaki says, and some have been implicated in the development of DSDs.

He notes that in roughly half of patients with DSDs, however, the genetic cause is unknown. So this database were assembling may now be used to predict some additional genes that are important in DSD and could be used for screening and diagnosis of DSDs, or even treatment and prevention.

The study also illuminated the relationship between the origin of the kidneys, adrenal glands, and gonads. They all originate from the PIM, but the timing and positioning is different, Sasaki says.

The adrenal glands, he says, develop from the anterior portion of the PIM, or that section closer to the head and arise early, while the kidney arises later from the posterior portion of the PIM. The gonadal glands span the PIM, with some regions developing earlier and others later.

In future studies, Sasaki and colleagues would like to continue teasing out the details and stages of gonadal development. Sasakis ultimate goal is to coax a patients own stem cells to grow into reproductive organs in the lab.

Some patients with DSDs dont have ovaries and testes, and some cancer patients undergo chemotherapy and completely lose their ovary function, Sasaki says. If you could induce a stem cell to grow into an ovary in the lab, you could provide a replacement therapy for these patients, allowing them to regain normal hormone levels and even fertility. With a precise molecular map to the developing gonad in hand, we are now one step closer to the this goal.

Kotaro Sasaki is an assistant professor in the Department of Biomedical Sciences in the University of Pennsylvania School of Veterinary Medicine.

Sasakis coauthors on the study were Penns Keren Cheng and Yasunari Seita; Kyoto Universitys Akiko Oguchi, Yasuhiro Murakawa, Ikuhiro Okamoto, Hiroshi Ohta, Yukihiro Yabuta, Takuya Yamamoto, and Mitinori Saitou; and Shiga University of Medical Sciences Chizuru Iwatani and Hideaki Tsuchiya. Sasaki and Saitou were corresponding authors.

The study was supported by a JST-ERATO Grant (JPMJER1104), Grant-in-Aid for Specially Promoted Research from JSPS (17H06098), the Pythias Fund, and the Open Philanthropy Fund from Silicon Valley Community Foundation (2019-197906).

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The origin of reproductive organs | Penn Today - Penn Today

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NEW YORK, New York, LEIDEN, Netherlands & CAMBRIDGE, Mass., May 04, 2021 (GLOBE NEWSWIRE) -- RTW Investments, LP (RTW), a global, full life-cycle investment firm that focuses on identifying transformational and disruptive innovations across the biopharmaceutical and medical technologies sectors, and ProQR Therapeutics N.V. (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through the creation of transformative RNA therapies for genetic eye diseases, today announced that Yarrow Biotechnology, Inc. (Yarrow) , a company newly created by RTW, has in-licensed exclusive rights to ProQRs antisense oligonucleotide technology (ASO) to develop and commercialize potential therapies for an undisclosed non-ophthalmic target. Yarrow is focused on developing ASO-based therapeutics for disorders with high unmet need.

Roderick Wong, MD, Managing Partner and Chief Investment Officer of RTW, said: We believe RNA-based therapies hold great promise to treat genetically-defined diseases. We are excited to partner with ProQR to in-license the first target to be developed in Yarrows pipeline.

Under the terms of the agreement, ProQR is eligible to receive up to $115 million of upfront and milestone payments, plus single digit percentage royalties on the net sales of any resulting products during the royalty term. ProQR will also have the right to receive an undisclosed percentage of equity in the form of shares of common stock of Yarrow. ProQR will be responsible for certain preclinical activities with reimbursement for the research costs by Yarrow, while Yarrow will be responsible for continuing development of the program and commercialization activities.

Gerard Platenburg, Chief Innovation Officer at ProQR, will join Yarrows board of directors.

Peter Fong, PhD, Head of Company Creation at RTW, said: Our partnership with ProQR fits perfectly into Yarrows mission to develop first-in-class ASO-based therapies for genetically-defined diseases. We look forward to a long and productive partnership.

Daniel A. De Boer, Founder and CEO of ProQR, said: As we focus ProQR on our core genetic eye disease strategy, we are pleased to partner with Yarrow to advance our technology in applications outside the eye, while generating value from this partnership and the broad applicability of our platform.

About RTW Investments, LP

RTW Investments, LP (RTW) is a New York-based, global, full life-cycle investment firm that focuses on identifying transformational and disruptive innovations across the biopharmaceutical and medical technologies sectors. As a leading partner of industry and academia, RTW combines deep scientific expertise with a solution-oriented investment approach to support emerging medical therapies and the companies and academics developing them.

About Yarrow Biotechnology, Inc.

Yarrow Biotechnology, Inc. (Yarrow) is a newly formed biotechnology company developing antisense oligonucleotide-based therapeutics for disorders with high unmet need. Yarrow has established a proprietary target discovery engine leveraging large-scale human genetics studies to uncover novel targets where there is a significant unmet need.

Yarrow is the latest new company created and backed by RTW Investments, LP.

About ProQR

ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies for the treatment of severe genetic rare diseases such as Leber congenital amaurosis 10, Usher syndrome and retinitis pigmentosa. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind. Learn more about ProQR at http://www.proqr.com.

Forward Looking Statements for ProQR

This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Such forward-looking statements include, but are not limited to, statements regarding the collaboration with RTW and Yarrow and the intended benefits thereof, including milestone and royalty payments from commercial product sales, if any, from the products covered by the collaboration and the issuance of equity in Yarrow to ProQR, as well as the potential of our technologies and product candidates. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our annual report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted by the COVID-19 pandemic; the likelihood of our clinical programs being executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers to supply materials for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in research and development; and general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law.

For ProQR Therapeutics N.V.

Investor Contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorHans VitzthumLifeSci AdvisorsT: +1 617 430 7578hans@lifesciadvisors.com

Media Contact:Cherilyn Cecchini, MDLifeSci CommunicationsT: +1 646 876 5196ccecchini@lifesciadvisors.com

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ProQR Therapeutics and Yarrow Biotechnology, an RTW Investments, LP Incubated Company, Announce Exclusive Worldwide License and Discovery...