Category Archives: Genetic medicine

Its not science fiction. Nowadays prospective parents cannot only know the sex of their unborn child but also learn whether it can supply tissue-matched bone marrow to a dying sibling and whether it is predisposed to develop breast cancer or Huntingtons disease all before the embryo gets implanted into the mothers womb. -Esthur Landhuis

Have you heard of designer babies? Or perhaps you saw or read My Sisters Keeper, a story about a young girl who was conceived through In Vitro Fertilization to be a genetically matched donor for her older sister with leukemia? The concept of selecting traits for ones child comes from a technology called preimplantation genetic diagnosis (PGD), a technique used on embryos acquired during In Vitro Fertilization to screen for genetic diseases. PGD tests embryos for genetic abnormalities, and based on the information gleaned, provides potential parents with the opportunity to select to implant only the healthy, non-genetically diseased embryos into the mother. But this genetic testing of the embryo also opens the door for other uses as well, including selecting whether you have a male or female child, or even the possibility of selecting specific features for the child, like eye color. Thus, many ethicists wonder about the future of the technology, and whether it will lead to babies that are designed by their parents.

Todays post is an exploration of the ethical issues raised by prenatal and preimplantation genetic diagnosis, written by Santa Clara Professor Dr. Lawrence Nelson, who has been writing about and teaching bioethics for over 30 years. Read on to examine the many ethical issues raised by this technology.

Prenatal and Preimplantation Genetic Diagnosis

Background:

The overwhelming majority of people on earth, due to a wide range of reasons, beliefs, bodily motives, and attitudessome good, some bad, and some in the moral neutral zonereproduce. They are the genetic, gestational, and/or social (rearing) parents of a child. Birth rates in some countries are at a historic low (Japans is beneath replacement with the consequent deep graying of an entire society). In others, mostly in the developing part of the world where infant and maternal morbidity and mortality (not to mention poverty and disease) are quite high, birth rates remain similarly high.

In the economically developed part of the world, the process of making and having babies has become increasingly medicalized, at least for those fortunate enough to have ready access to the ever more sophisticated tools and knowledge of obstetrical medicine. From the time prior to pregnancy (fertility treatments, in vitro fertilization) to birth (caesarean delivery, high tech neonatal intensive care) and in between (fetal surgery), medical science and technology can help many to reach the goal any good parent should want: the live birth of a healthy child to a healthy mother.

Medical and biological sciences can together determine whether a fetus will (or might) have over a thousand different genetic diseases or abnormalities

Parallel to obstetrical medicine, science and technology have progressed immensely in another are over the last 30 or so years. The Human Genome Project (and the related research it has stimulated) has generated an amazing amount of knowledge about the nature and identity of normaland abnormalhuman genetic codes. Now the medical and biological sciences can together determine whether a fetus will (or might) have over a thousand different genetic diseases or abnormalities. Ultrasound examination can look into the womb (quite literally) and see developmental abnormalities in the fetus (such as neural tube defects like spina bifida and anencephaly). Even a simple blood test done on a pregnant woman can determine whether the fetus she is carrying has trisomy 21 (down syndrome), a genetic condition associated with mental retardation and, not infrequently, cardiac and other health problems.

Pregnant women who have health insurance that covers obstetrical care (and many millions of American women donot), particularly if they are older (>35 years), are more or less routinely offered prenatal genetic diagnosis by their obstetricians. Chorionic villus sampling is a medical procedure that takes a few fetal cells from the placenta and can be done around 10 weeks after the womans last menstrual period. These cells can then be analyzed to determine the presence of genetic abnormalities. Amniocentesis is a medical procedure that obtains fetal cells from the amniotic fluid and is usually done later in pregnancy, typically after 14 weeks following the womans last menstrual period. When done by experienced medical professionals, both procedures carry about a 0.5% risk of spontaneous abortion. The genetic analysis done on these fetal cells can determine the presence of fatal genetic diseases (such as Tay-Sachs, trisomy 13 and 18), disease that can cause the born child much suffering (children with Lesch-Nyan, for example, compulsively engage in self-destructive behavior like lip chewing, while children with spinal muscular atrophy have severe, progressive muscle-wasting), and conditions that typically cause mental retardation (such as Fragile-X and Emanuel syndrome).

Although tremendous strides have been made in genetic sciences ability to detect chromosomal abnormalities, precious little success has been achieved in treating genetic disorders directly either prenatally or postnatally. Some symptomatic treatment may well be available, but almost nothing that will actually cure or significantly ameliorate the effects of the disease. A pregnant woman who wishes to avoid the birth of a child with genetic disease has little alternative but to seek termination of the pregnancy.

The science and technology of assisted reproduction (in this case in vitro fertilization [IVF]) meets the science and technology of obstetrical medicine in preimplantation genetic diagnosis (PGD). Embryos are created in vitro by mixing oocytes taken from the woman who intends to gestate one (or more) of them from a donor, and sperm taken from her partner or a donor. Genetic analysis is performed on one or few cells from each embryo, the loss of which does not affect the embryos ability to develop normally once implanted in a womb. Only those embryos free of detectable genetic abnormalities are then implanted in the womans womb in the hope that they will then attach to the uterine wall and develop normally. While success rates for implantation vary, many women have given birth following PGD. The main advantage of PGD over chorionic villus sampling and amniocentesis for many women and couples is that it avoid the need for a surgical abortion to end an undesired pregnancy, although it does result in discarding the affected embryos.

What ethical issues are raised by Prenatal Genetic Diagnosis and Preimplantation Genetic Diagnosis?

Prenatal genetic diagnosis (PrGD) and preimplantation genetic diagnosis (PGD) both raise a number of serious ethical questions and problems.

What role does money play in ethical issues with PrGD and PGD?

1. Both services are quite expensive (especially PGD which is typically not covered by even private insurance and has the added cost of IVF) and are not available to all who might need or want them. This raises difficult questions ofsocial justice and equity, including whether coverage for these services is morally responsible when social resources for all health care services (those that are life-saving and preventive) are seriously limited.

2. As PGD is generally paid for directly by the persons who utilize it, ethical questions arise aboutthe means clinics use to attract patients and the information they provide them about its risks and benefits. Clinicians are in a fiduciary relationship with their patients and are obligated to act so as to deserve and maintain the patients trust and confidence that their wishes and best interests are being faithfully served. Consequently, the marketing of infertility services ought to place the good of patients above other interests (especially a clinicians or clinics own economic interests), should not induce patients to accept excessive, unneeded, or unproven services, and should adhere to high standards of honesty and accuracy in the information provided to prospective patients.

What is the moral status of an embryo?

3. Both PrGD and PGD result in the destruction of embryos and fetuses.If, as some contend, all human embryos and fetuses have the same moral status as live-born persons, then they are entitled to basic rights, including the right not to be killed arbitrarily or for the purpose of advancing the interests of other persons. On this view, both PrGD and PGD would be seriously morally wrong. The opposing view would hold that embryos and fetuses lack any moral status whatsoever as they lack any properties, such as sentience or other cognitive traits, that determine moral standing and so can be destroyed at will.

Perhaps the more commonly heldand more ethically defensibleposition is that human embryos and fetuses deserve some modest moral status because they are alive, have some degree of potential to become human persons, and are in fact valued by moral agents whose views deserve at least some respect and deference from others. Nevertheless, they do not possess the full and equal moral standing of persons because they lack interests and other moral claims to personhood. Having a modest level of moral status does not preclude the destruction of embryos and fetuses for a morally serious reason or purpose, and the informed and conscientious choice of the persons who created the embryos to prevent the birth of a child with a serious genetic disease or abnormality is widely (though by no means universally) considered to be such a reason

Does PrGD and PGD lead to discrimination against the disabled?

4. Recently disability activists have strongly challenged what they deem to be the basic assumption underlying PrGD and PGD: reducing the incidence of disease and disability is an obvious and unambiguous good. They rightly criticize certain views that support this assumption: that the disableds enjoyment of life is necessarily less than for nondisabled people; that raising a child with a disability is a wholly undesirable thing; and that selective embryo discard or abortion necessarily saves mothers from the heavy burdens of raising disabled children. However,the ethical critique of the disability activists goes much deeper than this quite proper debunking of broadly drawn and inaccurate assumptions about life with any disability. First, they contend that the medical system tends to exaggerate the burden associated with having a disability and underestimates the functional abilities of the disabled. The activists also point out how medical language reinforces the negativity associated with disability by using such terms as deformity or defective embryo or fetus. Second, and more importantly, the disability activists claim that the promotion and use of PGD and traditional prenatal diagnosis sends a message to the public that negatively affects existing disabled people and fosters an increase in the oppression and prejudice from which they regularly suffer.

Adults who wish to reproduce are ethically obligated to do so in a responsible manner, and this means gathering and assessing fair and accurate information about what the future might hold for them and the child they might produce.

Insofar as individual clinicians do, in fact, exaggerate the problems and burdens of living as an individual with a disability or of living with a disabled person as a parent or family member, then they are doing a moral disservice to the people they are duty bound to be helping. Adults who wish to reproduce are ethically obligated to do so in a responsible manner, and this means (insofar as it is possible in a world about which we have imperfect knowledge) gathering and assessing fair and accurate information about what the future might hold for them and the child they might produce. Clinicians (especially genetic counselors) should endeavor to provide this kind of information, supplementedif at all possibleby the firsthand information that comes from those who have actually lived with disabilities of various kinds as parents of the disabled or from the disabled individuals themselves. On the other hand, these conditions are simply not utterly benign or neutral as each mayand often doesinvolve what can fairly be described as an undesirable event such as pain, repeated hospitalizations and operations, paralysis, a shortened life span, limited educational and job opportunities, limited independence, and do forth. [1]

Discrimination against persons with disabilities is just as morally repugnant as discrimination against persons based on race, religion, or sex, but it is not at all clear that PrGD and PGD reinforce or contribute to this in any manner. Regardless of how society might change (as it surelyought to change) its attitudes and practices to decrease or, better, eliminate the socially created disadvantages wrongly placed on the disabledand regardless of how individual persons might change their views on the prospect of knowingly having a child with a serious disability, other persons will prefer not to have a child with a serious disability, no matter how wonderful the social services, no matter how inclusive the society. It is this individual choice that PGD preserves, although the clinicians who offer PGD have a moral obligation to explore their own and their patients attitudes about, and understanding of, disability so these individual decisions can be made fairly and responsibly with accurate information about the real world of life with and without disability.

Should people be able to select the sex of their baby?

5. Both PrGD and PGD identify the sex of the embryo or fetus. This raisesthe question of whether it is ethically permissible for an embryo to be discarded or a fetus to be aborted because of sex. The selection of an embryos sex via PGD is done for two basic reasons: (1) preventing the transmission of sex-linked genetic disorders; and (2) choosing sex to achieve gender balance in a family with more than one child, to achieve a preferred order in the birth of children by sex, or to provide a parent with a child of the sex he or she prefers to raise. [2] While little extended ethical debate exists regarding the former, sex selection for the purpose of preventing the transmission of sex-linked genetic disease, the latter is the subject of heated ethical disagreement.

The ethical objections to sex selection for nonmedical reasons can be grounded both in the very act of deliberately choosing one sex over the other and the untoward consequences of sex selection, particularly if it is performed frequently. Sex selection can be considered inherently ethically objectionable because it makes sex a determinative reason to value one human being over another when it ought to be completely irrelevant: females and males as such always ought be valued equally and never differentially. Sex selection can also be ethically criticized for the undesirable consequences it may generate. Choice by sex supports socially created assumptions about the relative value and meaning of male and female, with the latter almost universally being considered seriously inferior to the former. By supporting assumptions that hold femaleness in lower social regard, sex selection enhances the likelihood that females will be the targets of infanticide, unfair discrimination, and damaging stereotypes.

Proponents of the ethical acceptability of sex selection would argue that a parents desire for family balancing can beand typically ismorally neutral. The defense of family balancing rests on the view that once a parent has a child of one sex, he or she can properly prefer to have a child of the other sex because the two genders are different and generate different parenting experiences.

To insist [that the experience of parenting a boy is different from that of parenting a girl] is not the case seems breathtakingly simplistic, as if gender played no role either in a persons personality or relationships to others. Gender may be partly cultural (which does not make it less real), but it probably is partly biological. I see nothing wrong with wanting to have both experiences. [3]

An opponent of sex selection for family balancing can argue that good parentswhether prospective or actualought never to prefer, favor, or give more love to a child of one sex over the other. For example, a morally good and admirable parent would never love a male child more than a female child, give the male more privileges than a female, or give a female more material things than a male simply because of sex or beliefs about the childs propergender. A virtuous and conscientious parent, then, ought not to think that, or behave as if, a child of one sex is better than one of the other sex, nor should a good parent believe or act as if, at bottom, girls are really different than boys in the ways that truly matter.

Sex selection is at least strongly ethically suspect, if not outright wrong

The argument in favor of sex selection for family balancing has to assume that gender and gender roles exist and matter in the lived world. For if they did not, then no reason would exist to differentiate the experience of parenting a male child from that of a female. However, it is precisely the reliance upon this assumption to which the opponent of sex selection objects: acceptingand perpetuatinggender roles inevitably both harms and wrongs both males and females, although females clearly suffer much more from them than males. While some gender roles or expectations are innocuous (e.g., men dont like asking for directions), the overwhelming majority (e.g., males areand should beaggressive, women areand should beself-sacrificing) are not. Consequently, given that sex selection is inevitably gendered and most gender roles and expectations restrict the freedom of persons to be who they wish to be regardless of gender, sex selection is at least strongly ethically suspect, if not outright wrong.

Watch: Designer Babies Ethical? L.A.s Fertility Institute Says Prospective Parents Can Choose Physical Traits, Not Just Gender, from CBS NEWS:

Questions 1. Is it ethical to use preimplantation genetic diagnosis to select the sex of your child? 2. Consider the arguments presented about PGD and the ethical issues it poses in regards to disabilities. Does PGD reinforce a message about the disabled that, as disability activists claim, negatively affects existing disabled people and fosters an increase in the oppression and prejudice from which they regularly suffer? 3. In the video above, the doctor interviewed named Dr. Steinberg says, Of course, once Ive got this science (of PGD), am I not to provide this to my patients? Im a physician. I want to provide everything science gives me to my patients. Do you agree with Dr. Steinbergs reasoning? Why or why not?

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Ethical Issues With Prenatal and Preimplantation Genetic ...

Bookshelf

A collection of biomedical books that can be searched directly or from linked data in other NCBI databases. The collection includes biomedical textbooks, other scientific titles, genetic resources such as GeneReviews, and NCBI help manuals.

A resource to provide a public, tracked record of reported relationships between human variation and observed health status with supporting evidence. Related information intheNIH Genetic Testing Registry (GTR),MedGen,Gene,OMIM,PubMedand other sources is accessible through hyperlinks on the records.

A registry and results database of publicly- and privately-supported clinical studies of human participants conducted around the world.

An archive and distribution center for the description and results of studies which investigate the interaction of genotype and phenotype. These studies include genome-wide association (GWAS), medical resequencing, molecular diagnostic assays, as well as association between genotype and non-clinical traits.

An open, publicly accessible platform where the HLA community can submit, edit, view, and exchange data related to the human major histocompatibility complex. It consists of an interactive Alignment Viewer for HLA and related genes, an MHC microsatellite database, a sequence interpretation site for Sequencing Based Typing (SBT), and a Primer/Probe database.

A searchable database of genes, focusing on genomes that have been completely sequenced and that have an active research community to contribute gene-specific data. Information includes nomenclature, chromosomal localization, gene products and their attributes (e.g., protein interactions), associated markers, phenotypes, interactions, and links to citations, sequences, variation details, maps, expression reports, homologs, protein domain content, and external databases.

A collection of expert-authored, peer-reviewed disease descriptions on the NCBI Bookshelf that apply genetic testing to the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions.

Summaries of information for selected genetic disorders with discussions of the underlying mutation(s) and clinical features, as well as links to related databases and organizations.

A voluntary registry of genetic tests and laboratories, with detailed information about the tests such as what is measured and analytic and clinical validity. GTR also is a nexus for information about genetic conditions and provides context-specific links to a variety of resources, including practice guidelines, published literature, and genetic data/information. The initial scope of GTR includes single gene tests for Mendelian disorders, as well as arrays, panels and pharmacogenetic tests.

A database of known interactions of HIV-1 proteins with proteins from human hosts. It provides annotated bibliographies of published reports of protein interactions, with links to the corresponding PubMed records and sequence data.

A compilation of data from the NIAID Influenza Genome Sequencing Project and GenBank. It provides tools for flu sequence analysis, annotation and submission to GenBank. This resource also has links to other flu sequence resources, and publications and general information about flu viruses.

A portal to information about medical genetics. MedGen includes term lists from multiple sources and organizes them into concept groupings and hierarchies. Links are also provided to information related to those concepts in the NIH Genetic Testing Registry (GTR), ClinVar,Gene, OMIM, PubMed, and other sources.

A project involving the collection and analysis of bacterial pathogen genomic sequences originating from food, environmental and patient isolates. Currently, an automated pipeline clusters and identifies sequences supplied primarily by public health laboratories to assist in the investigation of foodborne disease outbreaks and discover potential sources of food contamination.

A database of human genes and genetic disorders. NCBI maintains current content and continues to support its searching and integration with other NCBI databases. However, OMIM now has a new home at omim.org, and users are directed to this site for full record displays.

A database of citations and abstracts for biomedical literature from MEDLINE and additional life science journals. Links are provided when full text versions of the articles are available via PubMed Central (described below) or other websites.

A digital archive of full-text biomedical and life sciences journal literature, including clinical medicine and public health.

A collection of clinical effectiveness reviews and other resources to help consumers and clinicians use and understand clinical research results. These are drawn from the NCBI Bookshelf and PubMed, including published systematic reviews from organizations such as the Agency for Health Care Research and Quality, The Cochrane Collaboration, and others (see complete listing). Links to full text articles are provided when available.

A collection of resources specifically designed to support the research of retroviruses, including a genotyping tool that uses the BLAST algorithm to identify the genotype of a query sequence; an alignment tool for global alignment of multiple sequences; an HIV-1 automatic sequence annotation tool; and annotated maps of numerous retroviruses viewable in GenBank, FASTA, and graphic formats, with links to associated sequence records.

A summary of data for the SARS coronavirus (CoV), including links to the most recent sequence data and publications, links to other SARS related resources, and a pre-computed alignment of genome sequences from various isolates.

An extension of the Influenza Virus Resource to other organisms, providing an interface to download sequence sets of selected viruses, analysis tools, including virus-specific BLAST pages, and genome annotation pipelines.

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Genetics & Medicine - Site Guide - NCBI

The Department of Genetic Medicine at Weill Cornell Medicine is a highly specialized form of personalized medicine that involves the introduction of genetic material into a patients cells to fight or prevent disease. This experimental approach requires the use of information and data from an individual's genotype or specific DNA signature, to challenge a disease, select a medication or its dosage, provide a specific therapy, or initiate preventative measures specifically suited to the patient. While this technology is still in its infancy, gene therapy has been used with some success and offers the promise of regenerative cures.

As none of New York's premier healthcare networks, Weill Cornell Medicine's genetic research program includes close collaborations with fellow laboratories such as Memorial Sloan Kettering Cancer Center for stem cell projects, Weill Cornell Medical College in Qatar and Hamad Medical Corporation in Doha, Qatar and Bioinformatics and Biostatistical Genetics at Cornell-Ithaca.

Department of Genetic Medicine Services

Our translational research program includes many projects in the fields of genetic therapies and personalized medicine, and we arestudying gene therapy for a number of diseases, such as combined immuno-deficiencies, hemophilia, Parkinson's, cancer and even HIV using a number of different approaches.

Patients interested in gene therapy are invited to participate in our full range of services, including:

-diagnostic testing

-imaging

-laboratory analysis

-clinical informatics

-managed therapies

In addition, we offer genetic testing to provide options for individuals and families seeking per-emptive strategies for addressing the uncertainties surrounding inherited diseases.The Department of Genetic Medicine at Weill Cornell is a pioneer in the advancement of genetics for patients and their families. These are the strengths we draw upon as we collaborate with our integrated network of partners, including the #1 hospital in New York, New York Presbyterian, to make breakthroughs a reality for our patients.

For more information or to schedule an appointment, call us toll-free at 1-855-WCM-WCMU.

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Department of Genetic Medicine (Research) | - | Weill ...

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.

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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