Mutation history of the Roma/Gypsies
Mutation history of the Roma/Gypsies
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DOI：
10.1086/424759
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发表时间：
2004-10-01
影响因子：
9.8
通讯作者：
Kalaydjieva, L
中科院分区：
文献类型：
--
作者：
Morar, B;Gresham, D;Kalaydjieva, L
800万至1000万欧洲罗姆人/吉普赛人是具有共同血统的创始群体，他们随后分裂为多个社会上不同和地理上分散的吉普赛人群体。与其他创始人群不同的是，他们的家谱已经被广泛记录下来，吉普赛人的人口历史并没有完全被理解，而且由于缺乏书面记录，必须从目前的基因数据中推断出来。在这项研究中，我们使用了五个含有私人吉普赛突变的疾病基因座来检查一些缺失的历史参数和当前结构。我们分析了代表14个吉普赛人群体的832-1,363名无关对照的5个突变的频率分布，以及501个受影响家庭成员的染色体单倍型多样性。突变的共享和高携带率支持了强烈的创始人效应，吉普赛人和印度/巴基斯坦人染色体中先天性肌无力1267delG突变的身份为吉普赛人的印度起源提供了迄今最好的证据。然而，突变频率和单倍型分化的显著差异以及非常有限的单倍型共享表明吉普赛人的内部分化很强，并将吉普赛人描述为一个由多个亚分离株组成的创始种群。使用不同基因座的疾病单倍型聚合时间，我们估计整个吉普赛人群体的建立类似于32-40代之前，第二和第三代创始人事件发生在16-25代之前。多个亚分离株的存在，并保持着内交配，这表明了一种治疗复杂疾病的一般方法，其中最初的基因定位可以在来自单个吉普赛人组的大家庭中进行，而精细定位将依赖于对不同的亚分离株进行知情采样，并寻找与疾病表现出最强连锁不平衡的共同基因组区域。
The 8-10 million European Roma/Gypsies are a founder population of common origins that has subsequently split into multiple socially divergent and geographically dispersed Gypsy groups. Unlike other founder populations, whose genealogy has been extensively documented, the demographic history of the Gypsies is not fully understood and, given the lack of written records, has to be inferred from current genetic data. In this study, we have used five disease loci harboring private Gypsy mutations to examine some missing historical parameters and current structure. We analyzed the frequency distribution of the five mutations in 832-1,363 unrelated controls, representing 14 Gypsy populations, and the diversification of chromosomal haplotypes in 501 members of affected families. Sharing of mutations and high carrier rates supported a strong founder effect, and the identity of the congenital myasthenia 1267delG mutation in Gypsy and Indian/Pakistani chromosomes provided the best evidence yet of the Indian origins of the Gypsies. However, dramatic differences in mutation frequencies and haplotype divergence and very limited haplotype sharing pointed to strong internal differentiation and characterized the Gypsies as a founder population comprising multiple subisolates. Using disease haplotype coalescence times at the different loci, we estimated that the entire Gypsy population was founded similar to32-40 generations ago, with secondary and tertiary founder events occurring similar to16-25 generations ago. The existence of multiple subisolates, with endogamy maintained to the present day, suggests a general approach to complex disorders in which initial gene mapping could be performed in large families from a single Gypsy group, whereas fine mapping would rely on the informed sampling of the divergent subisolates and searching for the shared genomic region that displays the strongest linkage disequilibrium with the disease.