Model-based linkage analyses confirm chromosome 19q13.3 as a susceptibility locus for intracranial aneurysm
Model-based linkage analyses confirm chromosome 19q13.3 as a susceptibility locus for intracranial aneurysm
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DOI：
10.1161/01.str.0000259657.73682.03
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发表时间：
2007-04-01
期刊：
影响因子：
8.3
通讯作者：
Koizumi, Akio
中科院分区：
文献类型：
--
作者：
Mineharu, Youhei;Inoue, Kayoko;Koizumi, Akio
背景与目的：在家族性颅内动脉瘤（IA）的既往研究中，对5个不相关的家族进行了参数关联分析，其中4个家族采用显性模型提供最大概率对数（LOD）分数，1个采用隐性模型。每个家族与一个不同的基因座相连，表明基因座异质性。本研究旨在探讨日本IA家族与常染色体显性遗传模式是否支持与这些位点的联系。方法：使用GENEHUNTER程序进行全基因组连锁分析。我们从先前研究中用于非参数（无模型）连锁分析的29个家族中选择了具有显性模型的9个不相关IA家族的41个受影响成员，对其进行了仅受影响的参数连锁分析。结果：我们未能支持与先前报道的常染色体显性位点的联系。相反，我们发现了与染色体19q13.3的连锁，最大多点LOD评分为4.10。D19S198 ~ D19S902之间的LOD-1间隔（LOD评分为> -1的区域）为8.0 cM。结论：对日本显性IA家族的全基因组扫描证实了染色体19q13.3的位点，该位点也被报道为芬兰人群的候选位点。
Background and Purpose-In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci.Methods-We performed genomewide linkage analysis using the GENEHUNTER program. Affected-only parametric linkage analysis was used for 41 affected members in nine unrelated IA families with dominant models, which were selected from 29 families used for a nonparametric (model-free) linkage analysis in our previous study.Results-We failed to support the linkage to previously reported autosomal-dominant loci. Instead, we found linkage to chromosome 19q13.3 with a maximum multipoint LOD score of 4.10. The LOD-1 interval (regions with LOD scores of > 1) was 8.0 cM between D19S198 and D19S902.Conclusions-A genomewide scan for IA families with dominant models in Japan confirmed the locus at chromosome 19q13.3, which has also been reported as a candidate locus in a Finnish population.