Mapping a novel locus for familial atrial fibrillation on chromosome 10p11-q21
Mapping a novel locus for familial atrial fibrillation on chromosome 10p11-q21
复制标题
绘制染色体 10p11-q21 上家族性心房颤动的新位点
DOI：
10.1016/j.hrthm.2006.12.023
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发表时间：
2007-04-01
期刊：
影响因子：
5.5
通讯作者：
Chen, Yi Han
中科院分区：
文献类型：
--
作者：
Volders, Paul G. A.;Zhu, Qian;Chen, Yi Han
心房纤颤（AF）是最常见的心律失常，是美国的一个重要公共卫生问题，影响约220万美国人。最近，几个染色体位点和基因已被发现与家族性AF。然而，在大多数其他AF的情况下，遗传基础仍然知之甚少。目的本研究的目的是调查的分子基础上的家族性AF在荷兰的亲属group.METHODS我们分析了一个四代荷兰家庭中，AF分离为常染色体显性性状。排除与10 q22 -24、6 q14 -16、5 p13、KCNQ 1、KCNE 2、KCNJ 2和一些离子通道相关候选基因的连锁后，使用398个微卫星标记进行全基因组连锁扫描。0.00和单倍型分离的障碍被证明只有跨区域的染色体10。随后的精细标测在[θ] = 0.00时，D10 S568处的最大两点LOD评分为4.1982。在几个个体中的独特重组将所有受影响个体之间的共享区域缩小到Genethon图上的16.4 cM（侧翼标记：D10 S578和D10 S1652），其对应于染色体10 p11-q21。筛选出13个可能与房颤相关的候选基因。在其编码区（包括内含子剪接区）均未发现突变。结论我们在染色体10 p11-q21上发现了一个新的房颤基因座，为房颤的遗传异质性提供了进一步的证据。
BACKGROUND Atrial Fibrillation (AF), the most common cardiac arrhythmia, is a significant public health problem in the United States, affecting approximately 2.2 million Americans. Recently, several chromosomal loci and genes have been found to be associated with familial AF. However, in most other AF cases, the genetic basis is still poorly understood.OBJECTIVE The purpose of this study was to investigate the molecular basis of familial AF in a Dutch kindred group.METHODS We analyzed a four-generation Dutch family in which AF segregated as an autosomal dominant trait. After the exclusion of linkage to 10q22-24, 6q14-16, 5p13, KCNQ1, KCNE2, KCNJ2 and some ion-channel-associated candidate genes, a genome-wide linkage scan using 398 microsatellite markers was performed.RESULTS Two-point logarithms of odds (LOD) scores >1 at recombination fraction [theta] = 0.00 and a haplotype segregating with the disorder were demonstrated only across regions of chromosome 10. Subsequent fine mapping gave a maximum two-point LOD score of 4.1982 at D10S568 at [theta] = 0.00. Distinct recombination in several individuals narrowed the shared region among all affected individuals to 16.4 cM on the Genethon map (flanking markers: D10S578 and D10S1652), which corresponds to chromosome 10p11-q21. Thirteen candidate genes residing in this region, which could be associated with AF, were screened. No mutation has been found in their coding regions including the intron splice regions.CONCLUSION We identify a novel locus for AF on chromosome 10p11-q21, which provides further evidence of genetic heterogeneity in this arrhythmia.