Category Archives: Genetic medicine

Advances in molecular biology and human genetics, coupled with the completion of the Human Genome Project and the increasing power of quantitative genetics to identify disease susceptibility genes, are contributing to a revolution in the practice of medicine. In the 21st century, practicing physicians will focus more on defining genetically determined disease susceptibility in individual patients. This strategy will be used to prevent, modify, and treat a wide array of common disorders that have unique heritable risk factors such as hypertension, obesity, diabetes, arthrosclerosis, and cancer.

The Division of Genetic Medicine provides an academic environment enabling researchers to explore new relationships between disease susceptibility and human genetics. The Division of Genetic Medicine was established to host both research and clinical research programs focused on the genetic basis of health and disease. Equipped with state-of-the-art research tools and facilities, our faculty members are advancing knowledge of the common genetic determinants of cancer, congenital neuropathies, and heart disease. The Division faculty work jointly with the Vanderbilt-Ingram Cancer Center to support the Hereditary Cancer Clinic for treating patients and families who have an inherited predisposition to various malignancies.

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Genetic Medicine : Division Home | Department of Medicine

Northwestern University provides a strong foundation in core genetic counseling skills and identifies each students strengths in order to ignite the passion and lifelong commitment to learning that is critical to professional development. Graduates not only feel extremely capable in multiple clinical settings and specialties, but also recognize how valuable their training has been in preparing them for expanded genetic counseling careers.

Since the inception of the Northwestern University Graduate Program in Genetic Counseling in 1990, the leaders of the program have strived to look to the future of the genetic counseling profession to help guide the overall administration and curriculum. The field of genetics has evolved rapidly over time, and graduate programs need to be aware of the changes that will continue to shape and influence the profession. Northwestern has continued to successfully evolve to meet these changing needs. There are several strengths that allow Northwestern to maintain this cutting edge:

This unique combination, along with the personalized attention a student receives during their training, creates an exciting learning environment and is one of the major strengths of the Northwestern program. We believe our students deserve a strong science, research and psychosocial curriculum.

In addition, Northwestern is proud to offer one of the only dual degree programs available in Genetic Counseling and Medical Humanities and Bioethics.

The combination of the programs nationally recognized faculty, the diversity of clinical and patient experiences, and the cultural excitement of its location in Chicago makes this program unique, exciting and visionary!

Learn more about the program via the links below.

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Graduate Program in Genetic Counseling : Center for ...

Medicine in the post-genomic era

Genome Medicine publishes peer-reviewed research articles, new methods, software tools, reviews and comment articles in all areas of medicine studied from a post-genomic perspective. Areas covered include, but are not limited to, disease genomics (including genome-wide association studies and sequencing-based studies), disease epigenomics, pathogen and microbiome genomics, immunogenomics, translational genomics, pharmacogenomics and personalized medicine, proteomics and metabolomics in medicine, systems medicine, and ethical, legal and social issues.

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DNA-PK inhibition boosts Cas9-mediated HDR

Transient pharmacological inhibition of DNA-PKcs can stimulate homology-directed repair following Cas9-mediated induction of a double strand break, and is expected to reduce the downstream workload.

Genomics of epilepsy

Candace Myers and Heather Mefford review how advances in genomic technologies have aided variant discovery, leading to a rapid increase in our understanding of epilepsy genetics.

CpG sites associated with atopy

Thirteen novel epigenetic loci associated with atopy and high IgE were found that could serve 55 as candidate loci; of these, four were within genes with known roles in the immune response.

Longitudinal 'omic profiles

A pilot study quantifying gene expression and methylation profile consistency over a year shows high longitudinal consistency, with individually extreme transcript abundance in a small number of genes which may be useful for explaining medical conditions or guiding personalized health decisions.

Ovarian cancer landscape

Exome sequencing of mucinous ovarian carcinoma tumors reveals multiple mutational targets, suggesting tumors arise through many routes, and shows this group of tumors is distinct from other subtypes.

NGS-guided cancer therapy

Jeffrey Gagan and Eliezer Van Allen review how next-generation sequencing can be incorporated into standard oncology clinical practice and provide guidance on the potential and limitations of sequencing.

ClinLabGeneticist

A platform for managing clinical exome sequencing data that includes data entry, distribution of work assignments, variant evaluation and review, selection of variants for validation, report generation.

Semantic workflow for clinical omics

A clinical omics analysis pipeline using the Workflow Instance Generation and Specialization (WINGS) semantic workflow platform demonstrates transparency, reproducibility and analytical validity.

Stephen McMahon and colleagues review treatments for pain relief, which are often inadequate, and discuss how understanding of the genomic and epigenomic mechanisms might lead to improved drugs.

View more review articles

Errors in RNA-Seq quantification affect genes of relevance to human disease

Robert C and Watson M

Genome Biology 2015, 16:177

Exploiting single-molecule transcript sequencing for eukaryotic gene prediction

Minoche AE, Dohm JC, Schneider J, Holtgrwe D, Viehver P, Montfort M, Rosleff Srensen T, Weisshaar B et al.

Genome Biology 2015, 16:184

Analysis methods for studying the 3D architecture of the genome

Ay F and Noble WS

Genome Biology 2015, 16:183

Graded gene expression changes determine phenotype severity in mouse models of CRX-associated retinopathies

Ruzycki PA, Tran NM, Kefalov VJ, Kolesnikov AV and Chen S

Genome Biology 2015, 16:171

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Genome Medicine

Graduate Medical Education (GME): Medical Genetics

Maximilian Muenke, MD

Eligibility CriteriaCandidates with the MD degree must have completed an accredited U.S. residency training program and have a valid U.S. license. Previous training is usually in, but not limited to, Pediatrics, Internal Medicine or Obstetrics and Gynecology.

OverviewThe NIH has joined forces with training programs at the Children's National Medical Center, George Washington University School of Medicine and Washington Hospital Center. The combined training program in Medical Genetics is called the Metropolitan Washington, DC Medical Genetics Program. This is a program of three years duration for MDs seeking broad exposure to both clinical and research experience in human genetics.

The NIH sponsor of the program is National Human Genome Research Institute (NHGRI). Other participating institutes include the National Cancer Institute (NCI), the National Eye Institute (NEI), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Child Health and Human Development (NICHD), the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Mental Health (NIMH). Metropolitan area participants include Children's National Medical Center (George Washington University), Walter Reed Army Medical Center, and the Department of Pediatrics, and the Department of Obstetrics and Gynecology at Washington Hospital Center. The individual disciplines in the program include clinical genetics, biochemical genetics, clinical cytogenetics, and clinical molecular genetics.

The primary goal of the training program is to provide highly motivated physicians with broad exposure to both clinical and research experiences in medical genetics. We train candidates to become effective, independent medical geneticists, prepared to deliver a high standard of clinical genetics services, and to perform state-of-the-art research in the area of genetic disease.

Structure of the Clinical Training Program

RotationsThis three year program involves eighteen months devoted to learning in clinical genetics followed by eighteen months of clinical or laboratory research.

Year 1Six months will be spent on rotation at the NIH. Service will include time spent on different outpatient genetics clinics, including Cancer Genetics and Endocrine Disorders and Genetic Ophthalmology; on the inpatient metabolic disease and endocrinology ward; on inpatient wards for individuals involved in gene therapy trials; and on the NIH Genetics Consultation Service.

Three months will be spent at Children's National Medical Center and will be concentrated on pediatric genetics. Fellows will participate in outpatient clinics, satellite and outreach clinics. They will perform consults on inpatients and patients with metabolic disorders and on the neonatal service. Fellows will be expected to participate in the relevant diagnostic laboratory studies on patients for whom they have provided clinical care.

One month will be spent at Walter Reed Army Medical Center and will concentrate on adult and pediatric clinical genetics. One month will be spent at Washington Hospital Center on rotations in prenatal genetics and genetic counseling.

Year 2 Fellows will spend one month each in clinical cytogenetics, biochemical genetics, and molecular diagnostic laboratories. The remaining three months will be devoted to elective clinical rotations on any of the rotations previously mentioned. The second six months will be spent on laboratory or clinical research. The fellow will spend at least a half-day per week in clinic at any one of the three participating institutions.

Year 3This year will be devoted to research, with at least a half day per week in clinic.

NIH Genetics Clinic (Required)Fellows see patients on a variety of research protocols. The Genetics Clinic also selectively accepts referrals of patients requiring diagnostic assessment and genetic counseling. Areas of interest and expertise include: chromosomal abnormalities, congenital anomalies and malformation syndromes, biochemical defects, bone and connective tissue disorders, neurological disease, eye disorders, and familial cancers.

Inpatient Consultation Service (Required)Fellows are available twenty-four hours daily to respond to requests for genetics consultation throughout the 325-bed hospital. Written consultation procedures call for a prompt preliminary evaluation, a written response within twenty-four hours, and a subsequent presentation to a senior staff geneticist, with an addendum to the consult, as needed. The consultant service fellow presents the most interesting cases from the wards during the Post-Clinic Patient Conference on Wednesday afternoons during which Fellows present interesting clinical cases for critical review. Once a month the fellow presents relevant articles for journal club.

Metropolitan Area Genetics Clinics

Other Clinical Opportunities: Specialty Clinics at NIHThe specialty clinics of NIH treat a large number of patients with genetic diseases. We have negotiated a supervised experience for some of the fellows at various clinics; to date, fellows have participated in the Cystic Fibrosis Clinic, the Lipid Clinic, and the Endocrine Clinic.

Lectures, Courses and SeminarsThe fellowship program includes many lectures, courses and seminars. Among them are a journal club and seminars in medical genetics during which invited speakers discuss research and clinical topics of current interest. In addition, the following four courses have been specifically developed to meet the needs of the fellows:

Trainees are encouraged to pursue other opportunities for continuing education such as clinical and basic science conferences, tutorial seminars, and postgraduate courses, which are plentiful on the NIH campus.

Structure of the Research Training ProgramFellows in the Medical Genetics Program pursue state-of-the-art research related to genetic disorders. Descriptions of the diverse interests of participating faculty are provided in this catalog. The aim of this program is to provide fellows with research experiences of the highest caliber and to prepare them for careers as independent clinicians and investigators in medical genetics.

Fellows entering the program are required to select a research supervisor which may be from among those involved on the Genetics Fellowship Faculty Program. It is not required that this selection be made before coming to NIH.

In addition to being involved in research, all fellows attend and participate in weekly research seminars, journal clubs and laboratory conferences, which are required elements of each fellow's individual research experience.

Program Faculty and Research Interests

Examples of Papers Authored by Program Faculty

Program GraduatesThe following is a partial list of graduates including their current positions:

Application Information

The NIH/Metropolitan Washington Medical Genetics Residency Program is accredited by the ACGME and the American Board of Medical Genetics. Upon successful completion of the three year program, residents are eligible for board certification in Clinical Genetics. During the third residency year, residents may elect to complete either (a) the requirements for one of the ABMG laboratory subspecialties, such as Clinical Molecular Genetics, Clinical Biochemical Genetic
s or Clinical Cytogenetics, or (b) a second one year residency program (e.g., Medical Biochemical Genetics).

Candidates should apply through ERAS, beginning July 1 of the year prior to their anticipated start date. Candidates with the MD or MD and PhD degree must have completed a U.S. residency in a clinically related field. Previous training is usually in, but not limited to, Pediatrics, Internal Medicine or Obstetrics and Gynecology. Four new positions are available each year. Interviews are held during August and September.

Electronic Application The quickest and easiest way to find out more about this training program or to apply for consideration is to do it electronically.

The NIH is dedicated to building a diverse community in its training and employment programs.

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NIH Clinical Center: Graduate Medical Education (GME ...

BCH Division of Genetics and Genomics Seminar

Generating Cartilage from Human Pluripotent Stem Cells: A Developmental Approach.

Special Seminar

How Neurons Talk to the Blood: Sensory Regulation of Hematopoiesis in the Drosophila Model

Genetics Seminar Series

Neural Reprogramming of Germline Cells and Trans-Generational Memory in Drosophila

BCH Division of Genetics and Genomics Seminar

Genetics Seminar Series - Focused Seminars

Reflecting the breadth of the field itself, the Department of Genetics at Harvard Medical School houses a faculty working on diverse problems, using a variety of approaches and model organisms, unified in their focus on the genome as an organizing principle for understanding biological phenomena. Genetics is not perceived simply as a subject, but rather as a way of viewing and approaching biological phenomena.

While the range of current efforts can best be appreciated by reading the research interests of individual faculty, the scope of the work conducted in the Department includes (but is by no means limited to) human genetics of both single gene disorders and complex traits, development of genomic technology, cancer biology, developmental biology, signal transduction, cell biological problems, stem cell biology, computational genetics, immunology, synthetic biology, epigenetics, evolutionary biology and plant biology.

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Home | HMS Department of Genetics

Medical Genetics Faculty, Fellows & Staff: 2014

The University of Washington Department of Medicine is recruiting for one (1) full-time faculty position at the Associate Professor, or Professor level in the Division of Medical Genetics, Department of Medicine. This position is offered with state tenure funding.

Successful candidates for this position will have an M.D./Ph.D. or M.D. degree (or foreign equivalent), clinical expertise in genetics, and will be expected to carry out a successful research program. Highly translational PhD (or foreign equivalent) scientists may be considered. Although candidates with productive research programs in translational genetics/genomics and/or precision medicine will be prioritized, investigators engaged in gene therapy research may also be considered.

The position will remain open until filled. Send CV and 1-2 page letter of interest to:

Medical Genetics Faculty Search c/o Sara Carlson Division of Medical Genetics University of Washington seisner@u.washington.edu

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Medical Genetics at University of Washington

(Boston)--Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

###

Funding was provided by an ARRA stimulus grant (1RC2HL101535-01) awarded by the National Institutes of Health (NIH) to Boston University School of Medicine, Boston Medical Center and the Children's Hospital of Philadelphia. Additional funding was provided by K08 HL103771, FAMRI 062572_YCSA, an Alpha-1 Foundation Research Grant and a Boston University Department of Medicine Career Investment Award. Additional grants from NIH 1R01HL095993 and 1R01HL108678 and an ARC award from the Evans Center for Interdisciplinary Research at Boston University supported this work.

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Researchers produce iPSC model to better understand genetic lung/liver disease

Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

Story Source:

The above story is based on materials provided by Boston University Medical Center. Note: Materials may be edited for content and length.

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iPSC model helps to better understand genetic lung/liver disease

The order in which genetic mutations are acquired determines how an individual cancer behaves, according to research from the University of Cambridge, published today in the New England Journal of Medicine.

Most of the genetic mutations that cause cancer result from environmental 'damage' (for example, through smoking or as a result of over-exposure to sunlight) or from spontaneous errors as cells divide. In a study published today, researchers at the Department of Haematology, the Cambridge Institute for Medical Research and the Wellcome Trust/Medical Research Council Stem Cell Institute show for the first time that the order in which such mutations occur can have an impact on disease severity and response to therapy.

The researchers examined genetically distinct single stem cells taken from patients with myeloproliferative neoplasms (MPNs), a group of bone marrow disorders that are characterised by the over-production of mature blood cells together with an increased risk of both blood clots and leukaemia. These disorders are identified at a much earlier stage than most cancers because the increased number of blood cells is readily detectable in blood counts taken during routine clinical check-ups for completely different problems.

Approximately one in ten of MPN patients carry mutations in both the JAK2 gene and the TET2 gene. By studying these individuals, the research team was able to determine which mutation came first and to study the effect of mutation order on the behaviour of single blood stem cells.

Using samples collected primarily from patients attending Addenbrooke's Hospital, part of the Cambridge University Hospitals, researchers showed that patients who acquire mutations in JAK2 prior to those in TET2 display aberrant blood counts over a decade earlier, are more likely to develop a more severe red blood cell disease subtype, are more likely to suffer a blood clot, and their cells respond differently to drugs that inhibit JAK2.

Dr David Kent, one of the study's lead authors, says: "This surprising finding could help us offer more accurate prognoses to MPN patients based on their mutation order and tailor potential therapies towards them. For example, our results predict that targeted JAK2 therapy would be more effective in patients with one mutation order but not the other."

Professor Tony Green, who led the study, adds: "This is the first time that mutation order has been shown to affect any cancer, and it is likely that this phenomenon occurs in many types of malignancy. These results show how study of the MPNs provides unparalleled access to the earliest stages of tumour development (inaccessible in other cancers, which usually cannot be detected until many mutations have accumulated). This should give us powerful insights into the origins of cancer."

Work in the Green Lab is supported in party by Leukaemia and Lymphoma Research and Cancer Research UK.

Dr Matt Kaiser, Head of Research at Leukaemia & Lymphoma Research, said: "We are becoming more and more aware that a cancer's genetic signature can vary from patient to patient, and we are becoming better at personalising treatment to match this. The discovery that the order in which genetic errors occur can have such a big impact on cancer progression adds an important extra layer of complexity that will help tailor treatment for patients with MPNs. The technology to do this sort of study has been available only recently and it shows once again how pioneering research into blood cancers can reveal fundamental insights into cancer in general."

Dr ine McCarthy, Science Information Officer at Cancer Research UK, says: "The methods used in this pioneering research could help improve our understanding of how cancer cells develop mutations and when they do so. This interesting study suggests that the order in which genetic faults appear can affect how patients respond to different drugs - this insight could help doctors personalise treatment to make it more effective for each patient."

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Order matters: Sequence of genetic mutations determines how cancer behaves

TWO thirds of adult cancer cases were the result of genetic bad luck rather than unhealthy living, according to groundbreaking new research from the US.

Johns Hopkins University School of Medicine scientist Dr Bert Vogelstein said random mutations in DNA were the most common cause of cancer, with the rest caused by environment or inherited genes.

But he warned the finding should not be taken as a licence to drink or smoke to excess.

"This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors," Dr Vogelstein said.

"However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors."

Researchers compared the number of times organ stem cells divided with the risk of cancer in the tissues.

Those with the most divisions were generally more prone to tumours.

They found 22 of 31 cancer types were caused by random cell mutations - really just genetic misfortune which scientists could not otherwise explain.

The remainder, including smoking-related lung cancer and skin cancer, were related to heredity and environmental factors like exposure to harmful chemicals.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes', but the truth is that most of them simply had good luck," Dr Vogelstein said.

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Two thirds of cancer cases were genetic of bad luck: study