A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees
A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees
复制标题
对哥斯达黎加两个血统中易患严重双相情感障碍的基因进行全基因组筛选
DOI：
10.1073/pnas.93.23.13060
复制
发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Freimer, NB
中科院分区：
文献类型：
--
作者：
McInnes, LA;Escamilla, MA;Freimer, NB
双相情感障碍(BP)是一种以躁狂和抑郁发作为特征的衰弱综合征。我们设计了一项多阶段研究，以检测来自哥斯达黎加中央山谷的两个家系中所有易患严重BP(称为BP-I)的主要基因座，那里的人口主要是16-18世纪几个创始人的后裔。我们只考虑患有BP-I的个体，并筛选基因组与473个微卫星标记的连锁。我们使用了一个模型进行连锁分析，该模型结合了高表型复制比率和保守的外显率估计。我们在这项研究中的目标不是建立明确的连锁关系，而是检测这些家系中可能含有远BP-I主基因的所有区域。为了促进这一目标，我们评估了在我们的数据集中提供信息的标记提供每个基因组区域的覆盖的程度；我们估计至少94%的基因组已经被覆盖，这是通过先前的连锁模拟分析确定的预先指定的阈值。我们在这里报告了我们的基因组筛查远端BP-I基因座的结果，并指出了几个值得进一步研究的区域，包括18q、18p和11p中的片段，在这些片段中，观察到了两个或更多连续标记的提示性LOD分数。在1、2、3、4、5、7、13、15、16和17号染色体上也出现了超过我们阈值的一个或两个家系的孤立Lod评分。本基因组屏幕上突出显示的有趣区域将使用连锁不平衡(LD)方法进行跟踪。
Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes far BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen far BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.