Caroline Lieber

Understanding the Basics of NGS: From Mechanism to Variant Calling.

Identifying disease-causing mutations in DNA has long been the goal of genetic medicine. In the last decade, the toolkit for discovering DNA variants has undergone rapid evolution: mutations that were historically discovered by analog approaches like Sanger sequencing and multiplex ligation-dependent probe amplification (“MLPA”) can now be decoded from a digital signal with next-generation sequencing (“NGS”). Given the explosive growth of NGS-based tests in the clinic, it is of the utmost importance that medical practitioners have a fundamental understanding of the newest NGS methodologies. To that end, here we provide a very basic overview of how NGS works, with particular emphasis on the close resemblance between the underlying chemistry of Sanger sequencing and NGS. Using a pair of simple analogies, we develop an intuitive framework for understanding how high-confidence detection of single-nucleotide polymorphisms, indels, and large deletions/duplications is possible with NGS alone.

The emerging role of genetics professionals in forensic kinship DNA identification after a mass fatality: lessons learned from Hurricane Katrina volunteers.

Purpose: To explore the experience of medical genetics professionals who volunteered in the DNA identification efforts after Hurricane Katrina to identify “lessons learned” and plan for future recovery efforts.Methods: A web-based survey was administered to volunteers in the Fall of 2007.Results: Sixty-six individuals (75%) completed the survey. Eighty-six percent volunteered because they felt their skills as genetics professional were needed and 46% desired additional training on the molecular aspects of kinship analysis. Most (97%) reported that they would like to see the genetics community become actively involved in further developing the role of genetics professionals in mass fatality response. All respondents (100%) would volunteer again.Conclusion: Developing a registry of volunteers and educational materials tailored to the needs of genetics professionals should be explored as a mechanism to prepare the genetics community to play an active role in future mass fatality response.

Iona College Community Centered Family Health History Project: Lessons Learned from Student Focus Groups

The Community Centered Family Health History project was initiated to create accessible family health history tools produced by and for the community. The project goal was to promote increased community engagement in health education by encouraging conversations among family members that would translate knowledge of family health history into healthy lifestyle choices. As one of seven community partners, Iona College participated in customizing and beta-testing the Does It Run in the Family? toolkit. Twenty-nine college students were engaged to recruit three relatives related by blood to provide feedback on the utility of the toolkit. The toolkit consists of two booklets—“A Guide to Family Health History” and “A Guide to Understanding Genetics and Health”—explaining the importance of knowing and talking about health within the family as well as basics about how conditions are passed down through generations. Twenty-two of the twenty-nine students participated in focus groups to discuss their reactions to participation in the project. Students in the focus group reported that the study participants—students and their family members—found the toolkit to be user friendly and the experience a valuable one that prompted many to take positive steps toward good health.

Defining Moments: Coming Full Circle.

My “defining moment” has been more like a “defining interval,” developing over the last 3 years. After 18 years of working in a clinical setting, my focus has switched from educating patients to educating othersabout genetics. My experiences with a variety of educational programs have convinced me of the pressing need to broaden the genetic counselor’s role to accommodate widespread educational outreach. Additionally, two other themes have recurred consistently and satisfyingly. One theme is that outreach impacts the personal and professional growth of those involved in the shared experience. The other theme is that the lessons I learned so long ago in graduate school can be used in ways I had not anticipated. My encounters have been with three primary audiences: the schools (including Sarah Lawrence College), the community, and other health care professionals. One of the first lessons I learned is that there is a need to reach out to the school-age population to make them aware of the human genetics field. Primary school students who are exposed to genetic diversity may appreciate the differences between people and thus, may approach the world more broadmindedly. High school and college students, if introduced to genetics in a more clinically oriented way, may choose a career in genetics which will foster diversity and increase the numbers of genetic health professionals in the workforce. The need to attract qualified individuals from diverse backgrounds to the field is escalating as the frontiers of human genetics expand. A second realization has been of the need to educate the public at large. We need to disseminate our growing body of genetic knowledge to consumers while correcting misconceptions about what clinical genetics can achieve; we need to impart intimidating genetic information to consumers in a sensitive and comprehensive manner, giving them the tools to make appropriate health-related decisions for their lives.

493PDA SURVEY OF GENETIC COUNSELLORS ABOUT THE NEEDS OF 18-25 YEAR OLDS FROM FAMILIES WITH HEREDITARY BREAST AND OVARIAN CANCER SYNDROME

ABSTRACT Aim: Despite evidence supporting the benefits of risk reduction, protocols for early detection and prevention among women from families affected by hereditary breast and ovarian cancer (HBOC) are not yet proven, and clinical trials have not been undertaken for patients aged 18 to 25. The absence of psychosocial data may leave genetic counsellors without uniform guidance on how to manage the care of these patients. This project sought to investigate how best to work with HBOC patients aged 18-25 given their unique developmental, familial, and medical challenges. Methods: Certified genetic counselors were recruited through the NSGCs Cancer Genetics Special Interest Group listserv. Researchers constructed an online survey which included 41 items and elicited information about: counsellor demographics, training, and practice settings; approaches to cancer risk assessment; and common challenges in work with 18- to -25-year-old patients. The survey was also informed by previous work by researchers with 18 to 25-year-olds with BRCA gene mutations. Researchers used a combination of grounded theory and content analysis on open-ended responses, supported and triangulated with statistical analysis. Results: Respondents experienced 18-25-year-old patients presenting for cancer risk assessment differently than older patients, and some reported adapting their counseling style to address these differences. Respondents differed in the extent to which they felt familiar with the developmental needs of patients in this age group. Respondents aged 39 and under reported familiarity with this stage in life, having more recently completed it; respondents aged 40 and over reported less familiarity with, and more interest in learning about, this age group. A primary challenge, reported primarily by counsellors aged 39 and under, is navigating family dynamics in the counselling room and addressing the developmentally labile young adult. Conclusions: With respect to BRCA-related cancer risk, where penetrance is incomplete and onset in early adulthood is rare, optimal screening and prevention protocols now exist. This shifts the risk management landscape from one of choice to one of adherence. A rich understanding of the trajectories of human growth over time might enhance the counsellors capacity to assess patients and their family members. Disclosure: All authors have declared no conflicts of interest.

Book Review: Catalog of Human Cancer Genes. McKusick's Mendelian Inheritance in Man for Clinical and Research Oncologists (Onco-MIM). By John J. Mulvihill, M.D. Johns Hopkins University Press, Baltimore, MD, 1999, 646 pp.,

John Mulvihill’s Catalog of Human Cancer Genes is precisely that—a catalog of human cancer genes. According to the author, its origin stems from several factors. First is the growing unwieldiness of the genetics “bible,” Mendelian Inheritance in Man(MIM). Due to additional entries attributable to discoveries from the Human Genome Project (HGP), MIM has become somewhat cumbersome to use. Thus the author has attempted to remove those citations from MIM (using MIM nomenclature) that are associated with neoplasia and has put them all into a single volume, containing all of the known “genes and/or disorders that predispose to or are associated with neoplasia.” In the Introduction the author describes several factors that went into the development of this volume. Dr. Mulvihill offers his explanation for why this book was written, how the book is organized, how it was prepared, and strategies for use of this book. As the author points out, the number of genes that lead to cancers that have been identified has grown dramatically since the inception of the HGP. At the time of publication, this catalog, extracted primarily from the 8th edition of MIM, includes 635 entries (6.2% of the MIM total entries): 424 represent phenotypes, disorders, and conditions; 213 discuss genes and proteins. A good way to become familiar with this book is to study the Table of Contents. The organization of the entries is a little unusual. The entries are listed by the organ system that is most likely to be affected by neoplasia. Many of the entries seem familiar, such as the various breast cancer syndromes, retinoblastoma, and xeroderma pigmentosum. Some entries come as a surprise, however, such as finding cystic fibrosis listed under small bowel tumors. Adenocarcinoma of the ileum was first reported in association with cystic fibrosis in 1987; however, this finding is certainly not the first symptom that comes to mind when considering this cystic fibrosis. Another interesting example is listed under the category of “Oral Tumors.” The Oral–Facial–Digital Syndromes 1 and 3 are generally characterized by oral frenula and clefting, digital asymmetry, and hypoplasia of the nasal alae (Jones, 1997). OFD is listed in this volume because some affected individuals have