Variable continental distribution of polymorphisms in the coding regions of DNA-repair genes.
DNA-repair pathways are critical for maintaining the integrity of the genetic material by protecting against mutations due to exposure-induced damages or replication errors. Polymorphisms in the corresponding genes may be relevant in genetic epidemiology by modifying individual cancer susceptibility or therapeutic response. We report data on the population distribution of potentially functional variants in XRCC1, APEX1, ERCC2, ERCC4, hMLH1, and hMSH3 genes among groups representing individuals of European, Middle Eastern, African, Southeast Asian and North American descent. The data indicate little interpopulation differentiation in some of these polymorphisms and typical FST values ranging from 10 to 17% at others. Low FST was observed in APEX1 and hMSH3 exon 23 in spite of their relatively high minor allele frequencies, which could suggest the effect of balancing selection. In XRCC1, hMSH3 exon 21 and hMLH1 Africa clusters either with Middle East and Europe or with Southeast Asia, which could be related to the demographic history of human populations, whereby human migrations and genetic drift rather than selection would account for the observed differences.
Mathonnet
Géraldine
G
Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Labuda
Damian
D
Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada. damian.labuda@umontreal.ca.|Département de Pédiatrie, Université de Montréal, 3175 Côte Sainte-Catherine, Montréal, Québec, H3T 1C5, Canada. damian.labuda@umontreal.ca.
Meloche
Caroline
C
Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Wambach
Tina
T
Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Krajinovic
Maja
M
Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada.|Département de Pédiatrie, Université de Montréal, 3175 Côte Sainte-Catherine, Montréal, Québec, H3T 1C5, Canada.
Sinnett
Daniel
D
Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada.|Département de Pédiatrie, Université de Montréal, 3175 Côte Sainte-Catherine, Montréal, Québec, H3T 1C5, Canada.
D000483:Alleles; D000596:Amino Acids / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D004641:Emigration and Immigration; D005091:Exons; D005787:Gene Frequency; D040961:Genetic Drift; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015233:Models, Statistical; D011110:Polymorphism, Genetic
D000596:Amino Acids