STUDIES OF GENOMIC IMPRINTING IN BIPOLAR DISORDER

描述：（改编自申请人的摘要） 临床科学家奖（K 08）提案是一项五年计划，旨在使 候选人发展成为一个独立的研究人员在遗传学 躁郁症作为一个受过全面训练的精神病医生， 在情感性精神障碍中，候选人对表现型有很好的把握。 这项建议为他在分子生物学方面的技能提供了广泛的发展。 遗传方法。也将有机会学习统计遗传学 方法.这将通过正式的课程工作，广泛的 在协作研究环境中的指导，以及实施 这项研究将是迈向更大规模研究的第一步， 研究躁郁症的遗传学导师将由 小J·雷蒙德·德保罗博士情感障碍遗传学的主任 约翰霍普金斯大学的研究小组和安德鲁·范伯格博士， 约翰霍普金斯医学遗传学中心的基因组印记。特丽医生 约翰霍普金斯公共学院遗传流行病学主任贝蒂说， 卫生部将在统计遗传学方法方面提供有价值的咨询。的 培训计划将通过基于假设的研究计划得到加强 印记基因的亲本特异性表达改变了 易患躁郁症这一假设源于临床 证据表明，在疾病的传播中， 连锁证据的父母的起源影响染色体18，并从 在基因组的其他区域中的亲本起源效应的连锁证据。 候选人打算利用现有的两个宝贵的两极 在DePaulo博士的指导下收集的疾病家族数据集 目前正在确认中的第三个。具体目标如下：1） 鉴定来自候选人基因中转录的单核苷酸多态性 双相情感障碍的区域在染色体1 8 q上; 2）寻找印记 双相情感障碍易感基因的18号染色体上的测试， mRNA的单等位基因表达;和3）进行亲本等位基因特异性的 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.