STUDIES OF GENOMIC IMPRINTING IN BIPOLAR DISORDER

描述：(改编自申请者摘要)这位导师 临床医生-科学家奖(K08)提案是一项五年计划，旨在使 成为遗传学领域独立研究人员的候选人 双相情感障碍。作为一名训练有素、有专科经验的精神病学家 在情感障碍方面，应聘者对表型有很好的把握。 这项提议为他在分子方面的技能提供了广泛的发展。 遗传方法。还将有机会学习统计遗传学 方法：研究方法。这将通过正式的课程作业来完成，广泛的 在协作研究环境中进行指导，并实施 这项研究将是迈向更大研究主体的第一步，目的是 研究双相情感障碍的遗传学。指导将由以下人员提供 J·雷蒙德·德保罗博士，情感障碍遗传学主任 约翰斯·霍普金斯大学的研究小组和安德鲁·范伯格博士，一位 约翰霍普金斯医学遗传学中心的基因组印记。特里博士 约翰·霍普金斯大学公共学院遗传流行病学主任比蒂说 健康将在统计遗传学方法方面提供有价值的咨询。这个 培训计划将通过基于假设的研究计划来加强 印记基因的亲本特异性表达改变了 易患双相情感障碍。这一假说源于临床 疾病传播中父母原籍效应的证据，来自 18号染色体上亲本起源效应的连锁证据，以及来自 在基因组的其他区域存在亲本效应的连锁证据。 候选人打算利用现有的两个有价值的两极分子 在DePaulo博士的指导下收集的障碍家庭数据集 作为目前正在确定的第三个。具体目标如下：1) 鉴定候选基因中转录的单核苷酸多态 染色体1 8q；2)上的双相情感障碍区域搜索印迹 18号染色体上双相情感障碍易感基因的检测 MRNA的单等位基因表达；以及3)执行亲本等位基因特异性 其他染色体区域的遗传分析。

DESCRIPTION: (Adapted from applicant's abstract) This mentored clinician-scientist award (K08) proposal is a five-year plan to enable the candidate to develop into an independent investigator in the genetics of bipolar disorder. As a fully trained psychiatrist with sub-specialty experience in affective disorder, the candidate has an excellent grasp of the phenotype. This proposal provides for extensive development of his skills in molecular genetic methods. There will also be opportunities to learn statistical genetic methods. This will be accomplished through formal course work, extensive mentorship in a collaborative research environment, and implementation of a study that will be the first step toward a larger body of research aimed at investigating the genetics of bipolar disorder. Mentorship will be provided by Dr. J. Raymond DePaulo, Jr., the director of the affective disorders genetics research group at Johns Hopkins, and by Dr. Andrew Feinberg, an expert on genomic imprinting at the Johns Hopkins Center for Medical Genetics. Dr. Terri Beaty, director of genetic epidemiology at the Johns Hopkins School of Public Health will provide valuable consultation in statistical genetics methods. The training program will be enhanced by a research plan based on the hypothesis that the parent-of-origin-specific expression of imprinted genes modifies susceptibility to bipolar disorder. This hypothesis derives from clinical evidence for a parent-of-origin effect in transmission of the disorder, from linkage evidence for a parent-of-origin effect on chromosome 18, and from linkage evidence for a parent-of-origin effect in other areas of the genome. The candidate intends to take advantage of two valuable existing bipolar disorder family data sets collected under the direction of Dr. DePaulo as well as a third currently being ascertained. The specific aims are as follows: 1) to identify transcribed single nucleotide polymorphisms in genes from a candidate region for bipolar disorder on chromosome 1 8q; 2) to search for imprinted bipolar disorder susceptibility genes on chromosome 18 by testing for monoallelic expression of mRNA; and 3) to perform parental-allele-specific genetic analysis of other chromosomal regions.