[Mapping genes of complex diseases in genetic isolates of Dagestan].
Original results of the analysis of genetic linkage between some genomic markers and two complex clinical phenotypes, schizophrenia and mental retardation, in pedigrees from Dagestan genetic isolates are described. Interpopulation differences in the epidemiology of the complex phenotypes were studied and in their genetic linkage was demonstrated. These differences are evidently related to the genetic structure of the isolates determined by their genetic history. The MR epidemiological index characterizing the lifetime morbid risk of schizophrenia varies in the Dagestan isolates studied from 0 to 4.95%, which is almost five times higher than the average worldwide population rate, 1%. Comparative genetic mapping permitted determination of the most probable genetic linkages and associations of loci from chromosomal regions 17p11.1-12, 3q13.3, and a locus from 22q with schizophrenia and locus 12q23 with mental retardation. There is evidence that this approach is effective for detailed study of the relationship between the genetic (allele and locus) and clinical heterogeneity of complex diseases, which favors successful identification of the genes determining them. The study of linkage disequilibrium (LD) in genetic isolates of Daghestan populations (which have a common genetic background) may be an effective methodological approach for revealing the numerous contradictory results of mapping of the same genes of complex disease performed by different researchers in different regions of the world.
Bulaeva
K B
KB
Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991 Russia. bulaeva@vigg.ru
Pavlova
T A
TA
Kurbanov
R M
RM
Bulaev
O A
OA
D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D003241:Consanguinity; D003610:Dagestan / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020412:Multifactorial Inheritance; D010375:Pedigree; D012559:Schizophrenia / Q000235:genetics*