The effect of inbreeding on aggregation of complex diseases in genetic isolates
The effect of inbreeding on aggregation of complex diseases in genetic isolates
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DOI：
10.1134/s1022795409080109
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发表时间：
2009-08-01
影响因子：
0.6
通讯作者：
Bulayeva, K. B.
中科院分区：
文献类型：
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作者：
Bulayev, O. A.;Pavlova, T. A.;Bulayeva, K. B.
我们研究了遗传过程在种族和人口统计学上不同的分离株对复杂疾病流行病学的影响。我们对达吉斯坦5个土著族群的长期研究揭示了10个具有精神分裂症相关疾病聚集性的遗传分离株。根据Neel的分类（1992），根据人口统计过程的持续时间，这些分离株属于初级和次级。我们发现，所检查的初级和次级分离株的平均人口年龄分别约为4000岁和700岁。研究近交水平F采用两种方法：一种是传统群体遗传学研究中的三代通婚结构分析，另一种是广泛谱系（11 ~ 13代）通婚结构分析。我们已经证明，使用第二种方法，F值在各种分离株中增加两到三倍。初生分离株的累积近交比次生分离株高2倍。与次级分离株相比，初级分离株显示出相对较高的遗传和临床同质性，同时具有较高的群体特异性复杂疾病病理聚集性。还证实，在初级分离株中观察到的重组和与疾病相关的基因组位点数量减少。因此，我们的研究表明，如果在初级分离株中而不是在次级分离株中进行，特别是在处理遗传异质性的近交人类种群时，复杂疾病的成本更低，基因制图也更耗时。
We have studied the effect of genetic processes in ethnically and demographically diverse isolates on the epidemiology of complex diseases. Our long-term studies of five indigenous Dagestan ethnic groups have revealed ten genetic isolates with aggregation of schizophrenia-related diseases. According to Neel's classification (1992), these isolates belong to primary and secondary depending on the duration of demographic process. We have found that the average demographic ages of the examined primary and secondary isolates were about 4000 and 700 years, respectively. The inbreeding level F was studied using two methods: analysis of marriage structure in three generations, which is traditional in population-genetic studies, and analysis of the same structure in extensive pedigrees (up to 11-13 generations). We have shown that with the second method, the F value increases two- to threefold in various isolates. The accumulated inbreeding in the primary isolates proved to be twofold higher than that in the secondary ones. Primary isolates have revealed relatively higher genetic and clinical homogeneity in combination with higher aggregation of population-specific complex disease pathology compared to secondary isolates. A decrease in observed recombinations and the number of genomic loci linked with the disease in primary isolates have been also demonstrated. Thus, our studies showed that complex diseases can be less expensive and mapping of genes for time-consuming if conducted in primary rather than in secondary isolates, in particular when dealing with genetically heterogeneous outbred human populations.