Yan Denise, Park Hong-Joon, Ouyang Xiao Mei, Pandya Arti, Doi Katsumi, Erdenetungalag Raadnabazar, Du Li Lin, Matsushiro Naoki, Nance Walter E, Griffith Andrew J, Liu Xue Zhong
Department of Otolaryngology, University of Miami, 1666 NW 12th Avenue, Miami, FL 33136, USA.
Hum Genet. 2003 Dec;114(1):44-50. doi: 10.1007/s00439-003-1018-1. Epub 2003 Sep 18.
Mutations in the GJB2 gene encoding connexin 26 (Cx26) are a major cause of autosomal recessive and sporadic cases of congenital deafness in most populations. The 235delC mutation of GJB2 is the most frequent known mutation in some east Asian populations, with a carrier frequency of approximately 1%. In order to study the origin of 235delC among east Asians, we analyzed single-nucleotide polymorphisms (SNPs) within the coding region of GJB2 and flanking the 235delC mutation. We observed significant linkage disequilibrium between 235delC and five linked polymorphic markers, suggesting that 235delC arose from a common founder. The detection of 235delC only in east Asians, but not in Caucasians, and the small chromosomal interval of the shared haplotype suggest that 235delC is an ancient mutation that arose after the divergence of Mongoloids and Caucasians. Similarly, the finding that this mutation appears on a single haplotype provides no support for the possibility that recurrent mutation is the explanation for the high frequency of the allele.
编码连接蛋白26（Cx26）的GJB2基因突变是大多数人群中常染色体隐性和散发性先天性耳聋的主要原因。GJB2基因的235delC突变是一些东亚人群中最常见的已知突变，其携带者频率约为1%。为了研究东亚人群中235delC突变的起源，我们分析了GJB2编码区及235delC突变侧翼的单核苷酸多态性（SNP）。我们观察到235delC与五个连锁多态性标记之间存在显著的连锁不平衡，这表明235delC源自一个共同的始祖突变。仅在东亚人群而非高加索人群中检测到235delC突变，以及共享单倍型的小染色体区间，表明235delC是一个古老的突变，发生在蒙古人种和高加索人种分化之后。同样，该突变出现在单一单倍型上的发现不支持反复突变是该等位基因高频率的解释这一可能性。
