Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13
Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13
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DOI：
10.1007/s10048-007-0113-1
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发表时间：
2008-05-01
期刊：
影响因子：
2.2
通讯作者：
Montagna, Pasquale
中科院分区：
文献类型：
--
作者：
Kemlink, David;Plazzi, Giuseppe;Montagna, Pasquale
在不宁腿综合征（restless legs syndrome，RLS）家系中定位了染色体12 q、14 q、9 p、2 q和20 p上的5个基因座（RLS 1-RLS 5），第一个基因座为隐性遗传，第二个基因座为常染色体显性遗传。进一步的RLS家庭的调查显示遗传位点异质性的证据。我们在一个意大利血统的大型RLS家族中进行了全基因组连锁分析，其中3代中有12名受影响的成员，使用5，861个单核苷酸多态性（SNP，6 K Illumina）。连锁分析是在常染色体显性模型下进行的，具有完全的等位基因，等位基因频率为0.003，表型率为0.005。全基因组扫描结果提示19号染色体上的连锁证据，标记rs754292和rs 273265之间的最大多点对数比值为2.61。在一组159个欧洲血统的三人组中，以家庭为基础的关联研究中复制了该位点。本研究提供了进一步的RLS位点的证据，从而支持RLS作为一个遗传异质性的复杂性状的图片。
Five loci for restless legs syndrome (RLS) on chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1-RLS5) have been mapped in RLS families, with a recessive in the first and autosomal-dominant mode of inheritance in the latter cases. Investigations of further RLS families showed evidence for genetic locus heterogeneity. We have conducted a genome-wide linkage analysis in a large RLS family of Italian origin with 12 affected members in 3 generations using 5,861 single nucleotide polymorphisms (SNP, 6K Illumina). Linkage analysis was performed under an autosomal-dominant model with a complete penetrance, an allele frequency of 0.003 and a phenocopy rate of 0.005. The genome-wide scan resulted in suggestive evidence for linkage on chromosome 19p with maximum multipoint logarithm of the odds score of 2.61 between markers rs754292 and rs273265. The locus was replicated in a family-based association study in a set of 159 trios of European origin. This study provides evidence for a further RLS locus, thus supporting the picture of RLS as a genetically heterogenous complex trait.