GENOME SCAN OF INTRACRANIAL ANEURYSM FAMILIES IMPLICATES CHROMOSOMES 19 AND X

颅内动脉瘤家族的基因组扫描涉及 19 号和 X 号染色体

• 批准号: 7600971
• 负责人: Gerardus C Tromp
• 金额: $ 0.51万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7600971
• 关键词: 14q; 19q12; Affect; Cardiovascular system; Cause of Death; Cerebrovascular Disorders; Cessation of life; Chromosomes; Chromosomes, Human, Pair 19; Computer Retrieval of Information on Scientific Projects Database; Data; Data Set; Early identification; Family; Funding; Genes; Genome Scan; Genotype; Grant; Imaging Techniques; Individual; Institution; Intracranial Aneurysm; Left; Lod Score; Maps; Membrane; Methods; Morbidity - disease rate; Neurologic; Numbers; Operative Surgical Procedures; Outcome; Patients; Physiology; Predisposition; Relative (related person); Research; Research Personnel; Resources; Rupture; Sampling; Siblings; Source; United States National Institutes of Health; cerebrovascular; cerebrovascular imaging; follow-up; genetic linkage analysis; improved; member; mortality; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cerebrovascular (CV) disease is the third leading cause of death in the U.S. and about one-quarter of the CV deaths are due to ruptured intracranial aneurysms (IA). Of those that survive rupture, more than half are left with neurological deficits. Elective surgery and treatment prior to rupture are very effective in preventing morbidity and mortality. Early identification of individuals susceptible to IA would therefore greatly enhance our ability to prevent most serious outcomes. Analysis of a genome scan of 48 affected sib pairs has now been completed. This is the first genome scan for IA. IA has resisted previous attempts to obtain family data because of its high mortality. Using extraordinary efforts, we obtained families with multiple affected members by using cerebrovascular imaging techniques to detect unruptured IA in siblings of IA patients. Several candidate regions have been implicated. The highest multipoint lod score (2.63) was obtained on chromosome 19 in the region 19q12-13. This gene-rich chromosome region contains a number of genes known to be involved in cardiovascular, cerebrovascular, and/or membrane physiology. Other tentative chromosomal regions implicated by this genome scan included chromosome Xp (lod score = 2.08), 7p (lod score = 1.67), 14q (lod score = 1.36), and 4p (lod score = 1.27). We have genotyped additional markers in these regions in this sample and a replicate sample of 91 ASPs. Linkage analysis confirmed linkage to chromosome 19 in the replicate sample. On chromosome 19, we obtained a lod score of 3.50 using the combined data. This lod score improved to 5.7 after including the number of affected relatives as a covariate, suggesting that families with more affected relatives more likely harbor a susceptibility locus on chromosome 19. We plan to follow up the result using fine mapping methods and to complete the genome scan on the replicate data set.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 脑血管（CV）疾病是美国第三大死亡原因，大约四分之一的CV死亡是由于颅内动脉瘤破裂引起的。在那些生存的破裂的人中，有一半以上的神经功能缺陷。破裂前的选择性手术和治疗在预防发病率和死亡率方面非常有效。因此，对容易患IA的个人的早期识别将大大增强我们防止大多数严重结果的能力。现已完成对48个受影响SIB对的基因组扫描的分析。 这是IA的第一次基因组扫描。 IA由于死亡率很高而抵制了以前获得家庭数据的尝试。通过非凡的努力，我们通过使用脑血管成像技术来获取IA患者兄弟姐妹中未破裂的IA，从而获得了多个受影响成员的家庭。几个候选地区已被牵涉。在19q12-13区的染色体19上获得了最高的多点LOD评分（2.63）。该富基因的染色体区域包含许多已知与心血管，脑血管和/或膜生理学有关的基因。该基因组扫描涉及的其他暂定染色体区域包括XP染色体XP（LOD得分= 2.08），7p（LOD得分= 1.67），14q（LOD得分= 1.36）和4P（LOD分数= 1.27）。 我们已经在该样品中这些区域中的其他标记和91个ASP的重复样本中进行了基因分型。 链接分析证实了重复样品中与19染色体19的联系。 在染色体19上，我们使用组合数据获得了3.50的LOD得分。 在包括受影响的亲属作为协变量之后，该LOD评分提高到5.7，这表明具有影响更多的亲戚的家庭更有可能携带19染色体上的易感性基因座。我们计划使用精细的映射方法跟踪结果，并在重复数据集上完成基因组扫描。