ASHG Affirms Essential Role of International Travel, Global Participation for Scientific Advancement

Posted By: David L. Nelson, 2018 President

In light of the United States Supreme Court’s decision to uphold the White House’s 2017 Executive Order limiting travel for citizens of select nations, I want to affirm, on behalf of the membership of our Society, that we remain committed to the knowledge that research in the U.S. benefits greatly from the presence and full participation of international researchers in laboratories around the country and world.

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ASHG noted in our March 2017 statement opposing the ban that nearly one-third of  members reside outside the U.S., and that cross-pollination of ideas across borders is essential for sparking new avenues of inquiry and establishing partnerships. The diversity of experience, perspective, and expertise that comes from a globally connected research community moves science forward, and that benefits all of us. As 2017 ASHG president Nancy Cox noted so eloquently at the time, as geneticists, “we are all students of human variation and we value – indeed, celebrate – the diversity that has contributed to our survival as a species.”

We affirm our commitment to serve and support the international human genetics community and continue to welcome participation of scientists from all nations in the Society’s work and events.

David L. Nelson, PhD, is 2018 President of ASHG. He is a Cullen Foundation Professor of Molecular and Human Genetics at the Baylor College of Medicine, Associate Director of the BCM Intellectual and Developmental Disabilities Research Center, and Director of the BCM Integrative Molecular and Biomedical Sciences Graduate Program.

Inside AJHG: A Chat with Garry Cutting

Posted By: Sara Cullinan, PhD, Deputy Editor, AJHG

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Garry R. Cutting, MD (courtesy Dr. Cutting)

Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month we check in with Garry Cutting, to discuss ‘Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity.’

AJHG: What prompted you to start working on this project?

Garry: This project is part of an ongoing effort to interpret the molecular consequences of all variants in the CFTR gene. The variants selected for this study are associated with a wide-range of disease severity, allowing us to determine the utility of functional assays for variants that associate with moderate to mild forms of disease.

AJHG: What about this paper project most excites you?

Garry: We were surprised to find that a number of the putative disease-causing missense variants had minimal effect on protein function and that predictive algorithms have difficulty interpreting these “minimal effect” variants. Conversely, it was reassuring to find that incorporation of functional data improves annotation using expert and ACMG/AMP criteria.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the large human genetics community?

Garry: Missense variants are challenging to interpret and many are labeled as variants of unknown significance. Our study indicates that classifying missense variants, especially those associated with intermediate severity of disease, will require functional testing in the appropriate context. Our work also shows that current predictive algorithms should be used with caution as they tend to overcall missense variants as deleterious.

AJHG: What advice do you have for trainees/young scientists?

Garry: The explosion of DNA variant information provides a wonderful opportunity to investigate their effect upon RNA transcription, RNA splicing, protein stability, and protein function. Individuals who become facile with these techniques will be highly valued as we move from DNA sequencing to variant annotation and elucidation of disease mechanism.

AJHG: Tell us something about your life outside the lab.

Garry: I really enjoy working with my hands to repair something broken or build something new. Unlike the long time frames that we experience in science, fixing something can produce results in a much shorter time frame. Sometimes things go wrong, but you always seem to learn something new when you undertake projects that are out of your established area of expertise. Consequently, I fully agree that circuit breakers and water supply values should be turned off before undertaking home projects.

Garry Cutting, MD, is an Aetna/U.S. Healthcare Professor of Medical Genetics at John Hopkins. He has been a member of ASHG since 1997. 

Welcome HHMI-ASHG Fellow, Sarah Abdallah

Posted By: Ann Klinck, ASHG Communications and Marketing Assistant

ASHG is excited to be partnering with the Howard Hughes Medical Institute (HHMI) for the HHMI-ASHG Medical Research Fellowship. We’re happy to welcome third-year Yale medical student, Sarah Abdallah, to the position.

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Sarah Abdallah, HHMI-ASHG Medical Research Fellow (Courtesy Ms. Abdallah)

This program allows medical, dental, and veterinary students to take a year off from training and perform mentored laboratory research with support of a grant. “Our hope is that the experience will ignite students’ passion for research and encourage them to pursue careers as physician-scientists,” says David Asai, HHMI’s senior director for science education in a press release.

Sarah was interested in the fellowship because “it seemed to provide access to a community of scientists and to enriching experiences on top of my research, like attending conferences and meetings.”

Sarah’s research is focused around obsessive compulsive disorder (OCD). Specifically, it involves looking for post-zygotic variants in whole-exome sequencing data from individuals with OCD and their parents. These variants arise spontaneously and are not inherited from parents. By identifying the post-zygotic variants, it may be possible to understand the contribution of such variation to OCD development, identify risk genes, and eventually find new treatments.

“I am hoping this project will contribute to the collective understanding of the genetic basis of OCD. Many people with OCD do well, but I have seen firsthand how it can present as a very disabling, persistent disorder, and current pharmacologic treatments are not completely effective for all patients,” Sarah said.

ASHG member and Sarah’s primary mentor, Thomas Fernandez, MD, is an assistant professor in the Child Study Center and of Psychiatry at Yale. Another ASHG member and her co-mentor, James Noonan, PhD, is an associate professor of genetics at Yale.

During her fellowship, Sarah is hoping to gain more experience in computational genomics and is seeking guidance on how to combine her clinical and research interests into a career. She trusts that people like Dr. Fernandez will be able help her find the right path. She is considering a career in child psychiatry and pediatrics, but “either way, I hope to keep contributing to research on the genomics of neurodevelopmental disorders along with my clinical practice,” she said.

Launched 29 years ago, the HHMI Medical Research Fellows Program supports each Fellow through a year-long research project with a mentor of the Fellow’s choosing, and facilitates peer networking among Fellows and alumni as well as seminars with senior investigators. For more information, see the Program website.

 

Genetics Outreach and Donations at Calvin Coolidge Senior High School

Posted By: Kanika Pulliam, Senior Manager, Education and Career Development Programs

On the overcast and rainy morning of May 10, the ASHG Education Team (Kelly Ventura, Senior Director of Education and Membership; Karen Hanson, Senior Manager, Education Programs; Evelyn Mantegani, Education Coordinator; and myself) headed to Calvin Coolidge Senior High School, a public school in northwest Washington, DC. The school houses an Academy of Health Sciences, which prepares students for college and careers in health-related professions.

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The ASHG Education Team talked genetics and related careers with students at Calvin Coolidge Senior High School in Washington, DC. (courtesy Kelly Ventura)

As ASHG was preparing to move our main offices to a new building, we discovered a lot of new and gently used lab equipment and supplies in our storage room. There were things like a PCR machine, water bath, and DNA gel electrophoresis items. The supplies were previously purchased to facilitate experiments with educators who developed lesson plans for high school students. With no future plans for the supplies, we decided to donate them to a local high school, and identified Coolidge High School with the help of former ASHG Genetics Education and & Engagement Fellow Teresa Ramirez.

The day of the visit, Kelly and Karen graciously drove in their monster cars for us to load up and transport the many boxes to the school. We were greeted by Zakiya Edens, Coordinator of the Career Academy. She led us to the Academy of Health Sciences room, where we discussed the science program and its strategy to motivate students to come to class and maintain good grades. Students in this special academy participate in additional classes and programs on top of their regular curriculum to prepare for college.

We then met with some academy students, followed by a biology class that was discussing basic genetic concepts and the structure of DNA. Karen and I talked about our roles at ASHG to give the students an idea of career options in the sciences beyond traditional professions like scientist or medical doctor. I shared how they can use their background and love for research to educate scientists and clinicians interested in human genetics. Karen connected to the students by discussing her role as a genetic counselor for the past 25 years and showed them how genetic counselors work with a team of medical professionals to offer the best advice to patients.

We enjoyed the experience of chatting with teachers, administrators, and students. We are now working with Coolidge High School to organize a visit from an ASHG Genetics Education Outreach Network (GEON) volunteer member, to help the teachers go through the donated items and plan experiments for the new school year. GEON is a network of ASHG members who volunteer their time to assist science teachers in building understanding of human genetics among students and the general public.

Kanika Pulliam, PhD, is Senior Manager of Education and Career Development Programs at ASHG. For more on ASHG’s programs for science students, visit our K-12 education website.

Member Survey: ASHG Needs Your Input

Posted By: Mona V. Miller, ASHG Executive Director

In the coming year, the ASHG Board of Directors will begin a strategic planning period, and is seeking your input on what we do well and what we can do even better. In particular, the Board would like to know how ASHG can best support, represent, and advocate for the dynamic, diverse, and interdisciplinary field of human genetics. The new strategic plan will help guide how ASHG can serve you as members and leverage our collective efforts to advance the field.

To this end, we hope to better understand our current members and your priorities for our work through an important member survey. Launching this week and administered by our partners at McKinley Advisors, the survey invites your feedback on topics like:

  • What are your professional needs and challenges?
  • How can we best represent our diverse membership and enhance programs that serve you?
  • What are the most pressing issues confronting the Society and the larger genetics community that we are well positioned to address?
  • How can we better engage you in Society service opportunities, whether in public education, outreach and advocacy programs, or volunteer engagement?

Thank you for your input, and please be on the lookout for these opportunities!

Biology of Genomes 2018: The Past and Future of Genomics

Posted By: Emily C. Glassberg, PhD Candidate, ASHG Communications Committee

A few weeks ago, I attended the 31st annual Biology of Genomes (BoG) meeting at Cold Spring Harbor. In addition to highlighting the amazing research that comprises the current state of genomics, this meeting highlighted the storied past and bright future of the field. The enthusiastic participation of attendees, both at the meeting and on Twitter, shows incredible energy and momentum as we try to understand the genome’s role in biology, evolution, and disease.

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Attendees network at Biology of Genomes 2018 (Credit: Constance Brukin; copyright CSHL)

Genomics Present

The seven scientific sessions covered functional genomics, medical genomics, computational genomics, and evolutionary genomics, as well as genome engineering. Seeing this varied body of work at a single meeting clearly demonstrates that theory, experiment, high-throughput screening, and countless forms of new technology and data analysis all play central roles in shaping our current understanding of the human genome.

And, while the human genome was the primary subject of study, non-human genomes got coverage as well. Highlighted research included the genomes of near relatives, like Neanderthals; to those of best friends, like dogs; to those of model organisms, like yeast. Crowd favorites included Jaemin Kim’s and Elaine Ostrander’s talks using dogs as a system to learn about the genetic basis of complex traits (for the science as well as the adorable pictures).

The scientific programming also included two keynote speakers, Wendy Bickmore and David Page. Bickmore discussed her group’s work on how 3D chromatin structure relates to the mechanism by which enhancers – particularly long-range enhancers – interact with promoters to regulate gene expression.

Bickmore’s emphasis on the need to assay enhancer function in vivo was echoed elsewhere at the meeting. In particular, Emma Farley spoke about high-throughput measurements of enhancer function in the model chordate Ciona. In combination, these talks sparked a conversation about whether current computational models are looking in the wrong places when it comes to predicting enhancer activity and specificity.

Page presented his group’s work on the evolution of sex chromosomes with an eye to understanding sex differences in health and disease. Page’s question of whether and how males and females “read their genomes differently” connected to broader questions that recurred throughout this year’s meeting –  how do we understand the genome dynamically? When and how does the same genome lead to different outcomes?

The ways in which the genome and its downstream effects change over time and space is a big open question, and this year’s BoG showcased many approaches to tackling it:

  • Ben Strober and Jonathan Griffiths both used time-course gene expression data to track how gene regulation changes throughout cellular differentiation and development.
  • Jake Yeung shared an example of dynamic chromatin interactions and rhythmic promoter-enhancer contacts that are connected to circadian rhythm.
  • Christina Leslie presented work on how the chromatin state of tumor specific T-cells changes during cancer progression and how that influences disease treatability.

And that’s just a sample of the exciting work in this space! While we don’t yet have clear answers to these questions, the research discussed at BoG reveals a landscape that is complex, nuanced, and fascinating. What a great time to be in genomics!

Genomics Past

In addition to discussions spanning the range of the current field of genomics, BoG included a brief talk in memoriam of molecular and developmental geneticist John Sulston, who passed away on March 6, 2018. Dr. Sulston was well known for his seminal work in the now-model organism C. elegans, as well as his role in the Human Genome Project. Eric Lander also toasted Jim Watson for his role in the Human Genome Project, and to celebrate his 90th birthday. Lander and other BoG organizers later apologized for the toast, as it was seen by many in the community as minimizing Watson’s history of racist and sexist commentary.

Genomics Future

And, finally, no meeting would be complete without a vision for the future of the field.

A panel on the Ethical, Legal, and Social Implications of genomics research included four perspectives on the promises and pitfalls of germline genome editing. While there is considerable excitement around using CRISPR to cure genetic disease, many issues remain regarding proof of safety as well as ensuring equal access to the technology. Following a lively discussion during the question-and-answer, the consensus seemed to be that germline genome editing is a distant future. In the meantime, we can focus on the application of currently available options, like genetic screening and assisted reproductive technologies.

The National Human Genome Research Institute (NHGRI) also engaged researchers in its current strategic planning initiative, which began in February 2018 and will be completed in 2020. NHGRI is collecting input on priority areas to help the institute live up to its mantra, The Forefront of Genomics.

Of course, the scientific discourse at Biology of Genomes isn’t limited to the talks. The three lively poster sessions were great opportunities to exchange ideas. And many spirited discussions took place during the coffee breaks, over the traditional Cold Spring Harbor banquet, and down at Blackford bar. All told, there’s a lot to look forward in genomics!

Emily C. Glassberg is a PhD Candidate in the Department of Biology at Stanford University. She serves on ASHG’s Communications Committee and has been an ASHG member since 2014.

Developing a ‘2020 Vision’ for Genomics

Guest Post By: Eric D. Green, MD, PhD, Director, National Human Genome Research Institute

The National Human Genome Research Institute (NHGRI) recently launched a new round of strategic planning that aims to establish a ‘2020 vision’ for genomics research. This ~two-year effort will position NHGRI to lead genomics research and its applications to human health and medicine in the new decade – keeping the Institute at the Forefront of Genomics.

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Eric D. Green, MD, PhD, Director of NHGRI (courtesy NHGRI)

The strategic planning process will emphasize discussions about emerging areas of genomics that are not well-defined, are poised to benefit from new investments, and are not specific to specific diseases or physiological systems. These include broadly applicable areas such as genomic technology development; genomic variation and its role in human disease; medical use of genomic information; and the ethical, legal, and social implications of genomics, among others. We will also focus on areas in which NHGRI expects to continue providing leadership with others, including the genomic bases of rare and common diseases as well as computational genomics and data science.

A key aspect of NHGRI’s strategic planning process will be engaging both experts and diverse public communities for input, especially given the increasing relevance of genomics in everyday life – from non-invasive prenatal genetic testing to the growing availability of consumer genomics.

The new NHGRI strategic plan will be published in October 2020 – specifically to commemorate the 30th anniversary of the launch of the Human Genome Project.

We hope that you will participate in this strategic planning process! In the coming months, NHGRI will be hosting workshops, town halls, social media conversations, and satellite meetings at scientific conferences. We have already held a virtual town hall, have upcoming events in Seattle, Palo Alto, and Atlanta, and will host a satellite meeting at the ASHG Annual Meeting in San Diego in October.

Anyone can now submit their ideas on the Institute’s dedicated strategic planning website on genome.gov and follow conversations on Twitter and Facebook using the hashtag #genomics2020.

We look forward to engaging with all of you as we collectively shape the future of genomics. See you in San Diego!

Eric D. Green, MD, PhD, is the Director of the National Human Genome Research Institute (NHGRI) at the U.S. National Institutes of Health (NIH), a position he has held since 2009.