Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Hum Genet. 2010 Sep;128(3):261-7. doi: 10.1007/s00439-010-0846-z. Epub 2010 Jun 13.
Numerous cultural aspects, mainly based on historical records, suggest a common origin of the Middle-Eastern Arab Muslim and Jewish populations. This is supported, to some extent, by Y-chromosome haplogroup analysis of Middle-Eastern and European samples. Up to date, no genomic regions that are shared among Arab Muslim and Jewish chromosomes and are unique to these populations have been reported. Here, we report of a rare achromatopsia-causing CNGA3 mutation (c.1585G>A) presents in both Arab Muslim and Oriental Jewish patients. A haplotype analysis of c.1585G>A-bearing chromosomes from Middle Eastern and European origins revealed a shared Muslim-Jewish haplotype, which is different from those detected in European patients, indicating a recurrent mutation stratified by a Jewish-Muslim founder effect. Comprehensive whole-genome haplotype analysis using 250 K single nucleotide polymorphism arrays revealed a large homozygous region of ~11 Mbp shared by both Arab Muslim and Oriental Jewish chromosomes. A subsequent microsatellite analysis of a 21.5 cM interval including CNGA3 and the adjacent chromosome 2 centromere revealed a unique and extremely rare haplotype associated with the c.1585G>A mutation. The age of the shared c.1585G>A mutation was calculated using the microsatellite genotyping data to be about 200 generations ago. A similar analysis of mutation age based on the Arab Muslim data alone showed that the mutation was unlikely to be the product of a recent gene flow event. The data present here demonstrate a large (11 Mbp) genomic region that is likely to originate from an ancient common ancestor of Middle-Eastern Arab Muslims and Jews who lived approximately 5,000 years ago.
大量的文化方面的证据，主要基于历史记载，表明中东阿拉伯穆斯林和犹太人群体具有共同的起源。这在一定程度上得到了对中东和欧洲样本的 Y 染色体单倍型分析的支持。迄今为止，尚未报道在阿拉伯穆斯林和犹太染色体中共享且仅存在于这些人群中的基因组区域。在这里，我们报告了一个罕见的导致全色盲的 CNGA3 突变（c.1585G>A），存在于阿拉伯穆斯林和东方犹太患者中。对来自中东和欧洲起源的携带 c.1585G>A 的染色体的单倍型分析显示，存在一个共享的穆斯林-犹太单倍型，与在欧洲患者中检测到的不同，表明存在由犹太-穆斯林创始效应分层的反复突变。使用 250 K 单核苷酸多态性阵列进行的全基因组单倍型综合分析显示，阿拉伯穆斯林和东方犹太染色体之间存在一个约 11 Mbp 的大纯合区域。随后对包括 CNGA3 和相邻 2 号染色体着丝粒在内的 21.5 cM 间隔的微卫星分析显示，与 c.1585G>A 突变相关的独特且极为罕见的单倍型。使用微卫星基因分型数据计算共享的 c.1585G>A 突变的年龄约为 200 代前。仅基于阿拉伯穆斯林数据的类似突变年龄分析表明，该突变不太可能是最近基因流动事件的产物。这里呈现的数据表明，一个大的（11 Mbp）基因组区域可能源自大约 5000 年前生活在中东的阿拉伯穆斯林和犹太人的一个古老共同祖先。
