Hurricane Harvey

Posted by: Mona Miller, ASHG Executive Director

As you have likely seen in the news, Hurricane Harvey has caused major flooding and difficult conditions in Houston and the surrounding cities. Our thoughts are with our members, colleagues, the broader scientific community in southeast Texas, and all affected – we hope you and your loved ones are safe.

You may know that The American Journal of Human Genetics editorial office is located in Houston. AJHG’s website notes that their staff is safe, but there might be delays in responding to editorial questions over the next week.

Given that the ASHG 2017 early registration deadline is today, we are providing an extension for those affected by the hurricane. Please email registration@ashg.org for details.

Our thoughts remain with everyone affected.

Work-Life Balance: Advice from a Geneticist

Posted By: Elisabeth Rosenthal, PhD, Member of the ASHG Communications Committee

Achieving work-life balance as a scientist is hard; the hours are long and can be unpredictable. Here’s some advice from Gail Jarvik, a member of ASHG’s Board of Directors, a physician and statistical geneticist at the University of Washington, and Head of the Division of Medical Genetics at UW.

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Gail Jarvik (far right) and her family celebrated her daughter’s graduation this spring. (courtesy Dr. Jarvik)

Elisabeth: You are a clinician, researcher, administrator, and your work requires a lot of traveling. You are also married with three children. How?

Gail: It can be done. It helps to be very organized. I also have a supportive spouse who introduced me to the concept of getting as much help as we could afford when our family was young. His parents were both academics and he was well-trained from watching how they made it work. I had never had a housekeeper. That was his idea—even before we had children.

Elisabeth: How old are your children now?

Gail: Our children are now 22, 20, and 14 years old. At this point, only our 14-year-old takes substantial time. However, aging parents are beginning to take more time.

Elisabeth: How did you adjust your work when you first had children?

Gail: I went into the office early in the morning. You can get a lot done before everyone else shows up. At that time, I stayed off email from 7 until 9 AM. It allowed me to focus without distraction. I would work for a couple more hours after the kids were in bed at night. It is a real advantage to be a statistical geneticist. I have always been able to work very productively from home.

Elisabeth: How did you arrange childcare?

Gail: Unfortunately, the Seattle area does not have great childcare options. My husband is also a physician-scientist, so we needed flexible help. We have had live-out nannies for 22 years now. We have treated this as professional positions with a vacation, sick days, and health and unemployment insurance. There have definitely been some challenges, but our current nanny has worked with us for 14 years. We know she truly loves our kids.

Elisabeth: Did you work on weekends?

Gail: Of course, but for the most part I have been able to work from home.

Elisabeth: Any not-so-proud moments?

Gail: Not too many. Or, at least, not very many that I recall. I was able to volunteer one half day a week at my children’s grade school for many years. For the most part my schedule was flexible enough to be at recitals, performances, games, etc. I limited traveling when my first two children were young. I did finish a grant at the hospital while in labor. It was my project in a larger PO1 competitive renewal, so it had to get done. The baby was early. The grant was on time and it was funded.

Elisabeth: Any parting advice?

Gail: It all works somehow. You do not need to do all of it yourself. I had to learn how to accept help from both professionals and friends. Final advice: it is OK to bring store-bought food to the school potluck.

Gail Jarvik, MD, PhD, is the Arno G. Motulsky Endowed Chair in Medicine, Joint Professor of Medicine and Genome Sciences, and Head of the Division of Medical Genetics at the University of Washington. She is also an Adjunct Professor of Epidemiology at the UW Medical Center and an Affiliate Member of the Fred Hutchinson Cancer Research Center. A longtime member of ASHG, she served on its Program Committee from 2009-12 and has been a Board member since 2015.

New CME Program: Cell-free DNA Testing

Posted by: Karen Hanson, ASHG Health Professional Education Programs Manager

ASHG is proud to announce our newest health professional educational program, “Prenatal cfDNA screening”. In response to rapid developments in prenatal cfDNA technology and concerns about its incorrect use, we developed this program to address a need for genetics education within the OB/GYN community, in collaboration with the Mayo Clinic and with help from colleagues from Kaiser Permanente California.

A needs assessment of this group suggested that their biggest challenges were communicating the fundamentals of prenatal cfDNA screening with patients and helping patients understand screening results. Based on these findings, the new program uses a case-based focus to model patient communication and review the basic science behind cfDNA technology, as well as discuss methods for incorporating this test into clinical practice. Our content was developed and reviewed by a team of experts in the field of prenatal care. The result is a program that includes three online education modules built around pre-test and post-test patient encounters, video case presentations using a standardized patient to demonstrate the integration of cfDNA screening into clinical practice, and point-of-care educational tools.

Above: Health Professional Education Programs Manager Karen Hanson describes ASHG’s genetics education programs for providers.

Similar to our previous educational programming for health professionals, our goal for “Prenatal cfDNA Screening” is to improve the practice of medicine and patient outcomes. We’re hoping that this program helps health professionals improve communication with their patients regarding prenatal screening options in general and prenatal cfDNA screening specifically. To encourage participation, this program is modular, so that each part can be viewed separately at one’s own pace. In addition, it is CME accredited through the Mayo Clinic College of Medicine and Science.

Karen Hanson, MS, MBA, CGC, is Health Professional Education Programs Manager at ASHG. Read more about ASHG’s educational programs for health professionals.

Bill Gates and Francis Collins to Headline ASHG 2017 Presidential Symposium

Posted by: Nancy J. Cox, ASHG President; and Peter C. Scacheri, Chair of ASHG’s Program Committee

We are pleased to share some exciting news with the ASHG community: this year’s Presidential Symposium will feature a discussion of global health and genomics between two absolute legends in the health and science world: Bill Gates, Co-chair and Trustee of the Bill & Melinda Gates Foundation, and Francis Collins, MD, PhD, Director of the U.S. National Institutes of Health.

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(L) Bill Gates, Co-chair and Trustee, Bill & Melinda Gates Foundation; (R) Francis Collins, MD, PhD, Director, National Institutes of Health

During the 90-minute symposium, taking place Wednesday, October 18, 5:00-6:30 pm, Dr. Collins and Mr. Gates will address these topics and selected audience questions in an informal, conversational format.

This event will be open to all ASHG scientific registrants, so if you haven’t registered yet, now’s a great time to do so. More details on the symposium, including security considerations and how to submit your questions, will be made available as the date approaches.

We look forward to seeing you in Orlando.

Nancy Cox, PhD, ASHG President, directs the Vanderbilt Genetics Institute and is the Mary Phillips Edmonds Gray Professor of Genetics. She is also the Director of and a Professor of Medicine in the Vanderbilt Division of Genetic Medicine. Peter C. Scacheri, PhD, is 2017 Chair of the ASHG Program Committee. He is a Professor in the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine, and has been a member of ASHG since 2006.

Inside AJHG: A Chat with Jay Shendure, Molly Gasperini, and Greg Findlay

Posted by: Sara Cullinan, Deputy Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview an author(s) of a recently published paper. This month, we check in with former AJHG Editorial Board member Jay Shendure (@JShendure) and his students, Molly Gasperini (@MollyGasp) and Greg Findlay (@TheNobleDust), to discuss their paper, “CRISPR/Cas9-Mediated Scanning for Regulatory Elements Required for HPRT1 Expression via Thousands of Large, Programmed Genomic Deletions.

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(L-R) Greg Findlay, MD/PhD student; Jay Shendure, MD/PhD, Principal Investigator; and Molly Gasperini, Graduate Student (courtesy Dr. Shendure)

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

Authors: Despite the many ways of annotating the noncoding genome, a fundamental question will always be what the consequences are when you make direct changes to genomic sequence. Now that CRISPR allows us to do exactly that with unprecedented ease, we wanted to leverage its power to look for distal regulatory elements that affect gene expression. We reasoned such elements are likely a reason why methods such as exome sequencing fail in a minority of patients, and we were curious if we could find any such elements for a well-studied Mendelian disease gene

AJHG: What about this paper/project most excites you?

Authors: We engineered literally thousands of large genomic deletions in a single experiment. Function aside, that was just a cool thing to have succeeded in. What we learned from the assay was interesting as well, in that there wasn’t a single element in our screen outside of the exons that was essential for the gene’s function. It’s important to validate CRISPR screens like this to make sure the programmed deletions are truly what’s responsible for the effect on the cells – in this case, drug resistance. When we did this, the results came to life even more. We observed with high resolution that even deletions that go very near the transcriptional start site of HPRT1 are still tolerated by the cells.

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

Authors: We only interrogated a single locus, so any biological claims from this paper must be limited to HPRT1’s expression in this cell type. However, we hope our method will be applied more broadly to understand the role of noncoding sequence in other disease genes’ expression, too – essentially scanning vast amounts of the genome in a multilayered way for functional importance. The benefits of generating more datasets like this are twofold to the human genetics community: 1) we’ll better understand noncoding mutations’ role in affecting any one disease gene, and 2) after enough loci are interrogated, we’ll know more about how the role of noncoding sequences varies across gene categories, cell types, and disorders.

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

Authors: Where you can, design experiments where the result is going to be interesting no matter which way it turns out. In this case, we asked a question and got what was effectively a negative result. Importantly, a negative result is not at all the same as a failed experiment (i.e. a technical failure). Obviously, we would have been delighted to discover critical distal regulatory elements, but apparently there aren’t any across the region that we scanned. But that’s still really interesting! Perhaps more so because it’s not what we expected. Too often, technically sound, negative results go unreported, and that doesn’t do anyone a service.

AJHG: And for fun, tell us something about your life outside of the lab.

Authors: Outside of the lab, Molly hangs out with her baby nephew, listens to Motown music, and helps organize the local and national Communication Science Conventions. Greg enjoys biking around the city, exploring nature, and watching sports. Jay’s life these days consists solely of chasing after his three kids, chasing after his lab, and absorbing Game of Thrones theories. A highlight for the whole Shendure lab is the annual retreat to the Cascade mountains, which provide the perfect backdrop for re-energizing, brainstorming the next wave of experiments to try, and having fun with colleagues.

Jay Shendure, MD/PhD, is a Professor of Genome Sciences and Principal Investigator at the University of Washington. A member of ASHG since 2009, he received the Society’s Curt Stern Award in 2012 and currently serves on its Awards Committee. Molly Gasperini, Graduate Student (Genome Sciences) and 2016 Epstein Trainee Award recipient, and Greg Findlay, MD/PhD Student (Genome Sciences), belong to the Shendure Lab.

ASHG’s New Policy Statement on Human Germline Genome Editing

Posted by: Derek Scholes, PhD, ASHG Director of Science Policy

I am delighted to announce that ASHG’s statement on germline genome editing was published today in The American Journal of Human Genetics. This statement, written by a workgroup co-led by Kelly Ormond and Doug Mortlock and approved by ASHG’s Board of Directors, gives the Society’s perspective on the use of CRISPR/Cas9 or other similar tools to alter the genome of an embryo or germ cell. Importantly, it incorporates feedback that members provided when the workgroup solicited their perspectives early in the writing of the statement.

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The Germline Genome Editing Workgroup asked for member input at the 2015 Business Meeting, before developing draft recommendations and writing the statement. L-R: Douglas Mortlock, Kelly Ormond, William (Andy) Faucett, Rosario Isari, Kiran Musunuru, and Lawrence Brody.

The statement makes three main points:

  1. Concurring with many in the scientific community who have considered this question, it declares that it would be inappropriate at the present to carry out germline genome editing culminating in pregnancy, given the many questions about its safety and the associated ethical issues.
  2. However, it says we should allow in vitro germline genome editing as part of research to explore possible future clinical applications, and there should be no prohibition on the use of public funds for this research.
  3. That said, it makes clear that the Society believes germline genome editing should only ever be performed in humans if several important criteria are met. There needs to be not only a compelling medical reason, backed up by a strong evidence base, but also the ethical and policy questions need to have been addressed through a public process.

ASHG did not reach these conclusions alone. Rather, the workgroup that wrote the statement included representatives from the Association of Genetic Nurses and Counsellors, the Canadian Association of Genetic Counsellors, the International Genetic Epidemiology Society, and the National Society of Genetic Counselors. These organizations endorsed the final statement, as did the American Society for Reproductive Medicine, the Asia Pacific Society of Human Genetics, the British Society for Genetic Medicine, the Human Genetics Society of Australasia, the Professional Society of Genetic Counselors in Asia, and the Southern African Society for Human Genetics. The statement is all the more powerful for enjoying support from such major organizations from across five continents, that represent a variety of scientific and clinical perspectives.

This position statement is the latest in a series that the Society issues periodically on a range of genetics policy issues and different uses of genetic information. If there is a topic that you would like the Society to consider addressing, please let us know by emailing policy@ashg.org.

Derek Scholes, PhD, is ASHG’s Director of Science Policy. To learn more about ASHG’s policy priorities and positions, visit the Policy page.

Advances in the Genetics of Alzheimer’s Disease at AAIC 2017

Posted By: Timothy J. Hohman, Assistant Professor of Neurology, Vanderbilt Memory & Alzheimer’s Center

I just returned from the Alzheimer’s Association International Conference (AAIC) in London. AAIC always covers an amazing breadth of the most recent advances in research and clinical care for Alzheimer’s Disease (AD), and this year placed a particular emphasis on biomarkers. More specifically, the focus was on how we can integrate the growing availability of in vivo biomarkers of AD neuropathology into diagnostic criteria for research, and into screening procedures for clinical trials.

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Timothy J. Hohman, PhD (courtesy Dr. Hohman)

The Potential of Biomarkers

Philip Scheltens, MD, PhD, from the VU University Medical Center in the Netherlands kicked off the meeting with an impassioned lecture on the present landscape of biomarkers in AD, and the future potential of biomarkers in screening, diagnosis, targeted treatments, and disease prevention. AD is characterized by two primary neuropathologies: extracellular plaques composed of the amyloid-β protein and neurofibrillary tangles composed of hyper-phosphorylated tau. Over the past ten years, there has been a growing emphasis on measuring these proteinopathies in vivo, including the development of positron emission tomography tracers for amyloid and tau, and the development of assays to measure these proteins in cerebrospinal fluid. In 2011, the National Institute on Aging and the Alzheimer’s Association convened four work groups to develop new research criteria for diagnosis that integrated biomarkers of amyloid deposition into the clinical criteria for dementia. This year’s conversations focused on taking steps towards diagnosis and screening that relied solely on biomarkers.

Dr. Schelten’s emphasis on the future of biomarkers set up a somewhat heated panel presentation laying out a new NIA-AA research framework to investigate Alzheimer’s disease. Led by Clifford Jack, MD, the proposed framework would place a greater emphasis on biomarkers of the two primary proteinopathies, while also emphasizing the measurement and characterization of neurodegeneration. The panel has provided the opportunity for the community to give feedback directly to the workgroup as they continue to refine the proposed framework. Certainly, this will be a critical issue in AD research in the coming year and has important implications for clinical trials, study design, and (eventually) clinical care.

Functional Pathways, GWAS Findings, and AD

This is a genetics blog, though, so let’s get into the genetics! The primary keynote session on the genetics of AD was given by Julie Williams, PhD, from Cardiff University. Dr. Williams provided an overview of where we currently stand in unraveling the genetic architecture of the disease, and called for an increased emphasis on uncovering functional pathways that underlie the known risk loci. Dr. Williams argued the innate immunity and inflammation are fundamental pathways in AD pathogenesis, and that the causal pathways of sporadic AD may be fundamentally distinct from familial forms that operate strictly through an amyloid pathway.

Research presented throughout the conference re-emphasized the importance of innate immunity, including new risk loci in common variant and rare variant analyses completed by the Alzheimer’s Disease Genetics Consortium that implicated innate immune pathways (e.g., LILRA5).  Additionally, many of the functional genomic approaches emphasized the importance of macrophage and monocyte expression in predicting AD, including 14 genes implicated in a genetically regulated transcriptomic analysis by Towfique Raj, PhD, from the Icahn School of Medicine.

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Data parasites and data philanthropists both have important roles to play in using big data to study Alzheimer’s. (courtesy Dr. Hohman)

Given the growing emphasis on biomarkers throughout the field of AD, it was also encouraging to see substantial growth in the size of endophenotype analyses, including a GWAS of cerebrospinal fluid biomarkers of AD by Yuetiva Deming, PhD, analyzing data from over 3,000 individuals. Simon Lovestone, PhD, gave an additional “big data” plenary lecture in which he laid out how large-scale European collaborations integrating electronic medical record data and other big data resources will change the way research is completed. He called on #DataParasites (those who perform secondary analyses on existing datasets) to make use of rich data resources to identify new treatment targets and #DataPhilanthropists (data providers) to continue to step up and provide open access to collected data. Large scale data collection, data sharing, and secondary data analysis are becoming central components of AD research.

Varied Approaches to #EndALZ

There were many other areas of focus: from advances in neuroimaging and large-scale omics, to a growing emphasis on sex differences, racial disparities, and pathways of resilience, and a growing acceptance of the heterogeneity in the neuropathological presentation of the disease. If you are interested in AD and want to learn more from a variety of perspectives, this is a fantastic conference to attend. The field of AD is necessarily interdisciplinary and this conference is a fantastic representation of that diversity. Multiple perspectives, approaches, and treatment pathways will be needed to beat this devastating disease. After another year and another great conference, I’m hopeful and inspired to keep working to #EndALZ. Join us!

Timothy J. Hohman, PhD, is an Assistant Professor of Neurology at the Vanderbilt Memory & Alzheimer’s Center. He has been part of the ASHG community since 2013.