Strong Linkage Disequilibrium for the Frequent GJB2 35delG Mutation in the Greek Population
Strong Linkage Disequilibrium for the Frequent GJB2 35delG Mutation in the Greek Population
复制标题
DOI：
10.1002/ajmg.a.32546
复制
发表时间：
2008-11-15
影响因子：
2
通讯作者：
Petersen, Michael B.
中科院分区：
文献类型：
--
作者：
Kokotas, Haris;Van Laer, Lut;Petersen, Michael B.
大约每1000名儿童中就有1名在出生时或幼儿期遭受严重或深度听力损失（语前耳聋）。高达40%的先天性、常染色体隐性、重度至重度听力障碍病例是由单个基因突变引起的；GJB2，编码连接蛋白26。在高加索人群中检测到的GJB2突变中，该基因的一个特定突变35delG占了大多数。先前的一些研究认为35delG突变的高频率反映了突变斑点的存在，而其他研究则支持共同创始人的理论。希腊是35delG突变携带者频率最高的国家之一（3.5%）。最近的一项研究提出了这种突变起源于古希腊的假设。我们对60名希腊耳聋患者进行了基因分型，发现35delG纯合，6个单核苷酸多态性（snp）突变和2个微卫星标记在GJB2基因内部或两侧。将患者的等位基因分布与60名希腊正常听力对照进行比较。在35delG突变与GJB2基因内部或侧面的标记之间发现了强烈的连锁不平衡。此外，我们在之前的研究中发现了一个共同的单倍型，这表明35delG突变的共同创始人。(C) 2008 Wiley-Liss, Inc。
Approximately one in 1,000 children is affected by severe or profound hearing loss at birth or during early childhood (prelingual deafness). Up to 40% of congenital, autosomal recessive, severe to profound hearing impairment cases result from mutations in a single gene; GJB2, that encodes the connexin 26 protein. One specific mutation in this gene, 35delG, accounts for the majority of GJB2 mutations detected in Caucasian polulations. Some previous studies have assumed that the high frequency of the 35delG mutation reflects the presence of a mutational blot spot, while other studies support the theory of a common founder. Greece is among the countries with the highest carrier frequency of the 35delG mutation (3.5%). and a recent study raised the hypothesis of the origin of this mutation in ancient Greece. We genotyped 60 Greek deafness patients homozygous for the 35delG, mutation for six single nucleotide polymorphisms (SNPs) and two microsatellite markers inside or flanking the GJB2 gene. The allele distribution in the patients was compared to 60 Greek normal hearing controls. A strong linkage disequilibrium was found between the 35delG mutation and markers inside or flanking the GJB2 gene. Furthermore, we found a common haplotype with a previous study, suggesting a common founder for the 35delG mutation. (C) 2008 Wiley-Liss, Inc.