The effect of inbreeding on aggregation of complex diseases in genetic isolates

The effect of inbreeding on aggregation of complex diseases in genetic isolates 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Russian Journal of Genetics Springer Journals

The effect of inbreeding on aggregation of complex diseases in genetic isolates

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Publisher
Springer Journals
Copyright
Copyright © 2009 by Pleiades Publishing, Ltd.
Subject
Biomedicine; Microbial Genetics and Genomics; Animal Genetics and Genomics; Human Genetics
ISSN
1022-7954
eISSN
1608-3369
D.O.I.
10.1134/S1022795409080109
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Russian Journal of GeneticsSpringer Journals

Published: Aug 25, 2009

References

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