Identification of a genetic locus for familial atrial fibrillation
Identification of a genetic locus for familial atrial fibrillation
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DOI：
10.1056/nejm199703273361302
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发表时间：
1997-03-27
影响因子：
158.5
通讯作者：
Roberts, R
中科院分区：
文献类型：
--
作者：
Brugada, R;Tapscott, T;Roberts, R
背景房颤是最常见的持续性心律失常，影响着200多万美国人，占65岁以上中风患者的三分之一。房颤的分子基础尚不清楚，姑息治疗用于控制心室率和预防全身栓塞。我们确定了一个家庭的26名成员，其中10人有心房颤动，分离作为一种常染色体显性遗传病。随后，我们确定了另外两个家庭中的疾病被链接到同一locus.Methods的多态性二核苷酸重复标记的300人的基因组进行筛选，使用一种非常规的策略，汇集的DNA样本分为两组（受影响的和未受影响的），这减少了约90%的样本量，然后进行连锁分析，以映射的位点。结果D10 S569和D10 S607在家系1中的lod值为3.60，位于10 q22-q24。在家庭2和3中的疾病位点也与相同的标记，与标记D10 S569和D10 S607，分别为6.02和5.35，当所有三个家庭的数据相结合。单倍型分析结果显示，该基因位于D10 S1694 ~ D10 S1786之间，间隔11.3厘摩。结论家族性房颤基因的鉴定将有助于阐明该病的分子基础，并为获得性房颤提供新的认识。汇集DNA样本进行分析的策略比传统的筛选更省时、更省钱，将来应该会加速基因图谱的进程。(C)1997年，马萨诸塞州医学会。
Background Atrial fibrillation, the most common sustained cardiac-rhythm disturbance, affects over 2 million Americans and accounts for one third of all strokes in patients over 65 years of age. The molecular basis for atrial fibrillation is unknown, and palliative therapy is used to control the ventricular rate and prevent systemic emboli. We identified a family of 26 members of whom 10 had atrial fibrillation that segregated as an autosomal dominant disease. We subsequently identified two additional families in which the disease was linked to the same locus.Methods We screened the human genome with 300 polymorphic dinucleotide-repeat markers using an unconventional strategy of pooling the DNA samples into two groups (affected and unaffected), which reduced the sample size by approximately 90 percent, before performing linkage analysis to map the locus. This made it possible to identify potential loci within a few weeks.Results The lod scores for markers D10S569 and D10S607, located at 10q22-q24, were 3.60 in Family 1. The disease locus in Families 2 and 3 was also linked to the same markers, with lod scores of 6.02 and 5.35 for markers D10S569 and D10S607, respectively, when data on all three families were combined. Haplotype analysis of the three families showed that the locus was between D10S1694 and D10S1786, an interval of 11.3 centimorgans.Conclusions Identification of the gene for familial atrial fibrillation will help to elucidate the molecular basis of the disease and provide insights into acquired forms. The strategy of pooling DNA samples for analysis is more time and cost effective than conventional screening and should accelerate the process of gene mapping in the future. (C) 1997, Massachusetts Medical Society.