Latini Veronica, Sole Gabriella, Varesi Laurent, Vona Giuseppe, Ristaldi Maria Serafina
Consiglio Nazionale delle Ricerche, Istituto di Neurogenetica eNeurofarmacologia (INN-CNR), Cagliari, Italy.
BMC Med Genet. 2008 Jul 28;9:73. doi: 10.1186/1471-2350-9-73.
Genetic isolates with a history of a small founder population, long-lasting isolation and population bottlenecks represent exceptional resources in the identification of disease genes. In these populations the disease allele reveals Linkage Disequilibrium (LD) with markers over significant genetic intervals, therefore facilitating disease locus identification. In a previous study we examined the LD extension on the Xq13 region in three Corsican sub-populations from the inner mountainous region of the island. On the basis of those previous results we have proposed a multistep procedure to carry out studies aimed at the identification of genes involved in complex diseases in Corsica. A prerequisite to carry out the proposed multi-step procedure was the presence of different degrees of LD on the island and a common genetic derivation of the different Corsican sub-populations. In order to evaluate the existence of these conditions in the present paper we extended the analysis to the Corsican coastal populations.
Samples were analyzed using seven dinucleotide microsatellite markers on chromosome Xq13-21: DXS983, DXS986, DXS8092, DXS8082, DXS1225, DXS8037 and DXS995 spanning approximately 4.0 cM (13.3 Mb). We have also investigated the distribution of the DXS1225-DXS8082 haplotype which has been recently proposed as a good marker of population genetic history due to its low recombination rate.
the results obtained indicate a decrease of LD on the island from the central mountainous toward the coastal sub-populations. In addition the analysis of the DXS1225-DXS8082 haplotype revealed: 1) the presence of a particular haplotype with high frequency; 2) the derivation from a common genetic pool of the sub-populations examined in the present study.
These results indicate the Corsican sub-populations useful for the fine mapping of genes contributing to complex diseases.
具有小创始群体历史、长期隔离和群体瓶颈的遗传隔离群体是鉴定疾病基因的特殊资源。在这些群体中，疾病等位基因与显著遗传区间内的标记显示出连锁不平衡（LD），因此便于疾病基因座的鉴定。在之前的一项研究中，我们研究了来自该岛内陆山区的三个科西嘉亚群体中Xq13区域的LD扩展情况。基于之前的这些结果，我们提出了一个多步骤程序，以开展旨在鉴定科西嘉岛复杂疾病相关基因的研究。实施所提出的多步骤程序的一个先决条件是该岛存在不同程度的LD以及不同科西嘉亚群体具有共同的遗传起源。为了评估本文中这些条件是否存在，我们将分析扩展到了科西嘉沿海群体。
使用位于Xq13 - 21染色体上的七个二核苷酸微卫星标记对样本进行分析：DXS983、DXS986、DXS8092、DXS8082、DXS1225、DXS8037和DXS995，跨度约为4.0厘摩（13.3兆碱基）。我们还研究了DXS1225 - DXS8082单倍型的分布，由于其低重组率，该单倍型最近被提议作为群体遗传历史的良好标记。
所获得的结果表明，该岛从中央山区到沿海亚群体的LD呈下降趋势。此外，对DXS1225 - DXS8082单倍型的分析显示：1）存在一种高频的特定单倍型；2）本研究中所检查的亚群体源自一个共同的基因库。
这些结果表明科西嘉亚群体对于复杂疾病相关基因的精细定位是有用的。
