Molecular genetic variation in the East Midlands, England: analysis of VNTR, STR and Alu insertion/deletion polymorphisms

Abstract

Background: Short tandem repeats (STRs) and variable number of tandem repeats (VNTRs) have been used successfully in disease analysis and studies of human evolution and population genetic diversity. However DNA-based comprehensive population genetic studies of the East Midlands, England are limited. Subjects and methods: To enlarge our understanding of genetic variation in the East Midlands, a study was conducted on five regional populations: north-west Derbyshire, north-east Derbyshire, south Derbyshire, Nottinghamshire and Leicestershire. Blood samples were collected from donors whose ancestors had lived in the region for at least three generations. Seven VNTRs (MS1 (D1S7), MS31 (D7S21), MS43A (D12S11) and YNH24 (D2S44), D1S80, APOB, YNZ22 (D17S5)), six STRs (HumTHO1, HumVWA31A, HumF13A01, HumFESFPS, HumCSF1PO, HumTPOX) and six Alu insertion/deletion polymorphisms (TPA25, ACE, PV92, F13B, APO, D1) were analysed in approximately 500 individuals. Allele or bin frequencies were calculated using gene counting and fixed bin methods. The chi-square method and exact tests were used to assess Hardy-Weinberg equilibrium. Genetic distances were calculated using Nei's D_A method and correspondence analysis was used to assess population affinities. Results: The overall pattern of allele frequencies was similar to many European and UK populations for a number of genetic systems. Overall heterogeneity was observed for five loci: MS43A, MS31, HumF13A01, HumFESFPS and HumTHO1. Twenty-three of 190 pairwise population comparisons were also statistically significant at the 5% level. Average molecular genetic system heterozygosity was 1.5 times higher than observed with conventional blood group systems. G_ST values for molecular systems were also higher than conventional systems (0.012 vs 0.005) and suggest a low to moderate level of differentiation. Conclusion: The allele frequency spectrum and inter-population comparisons show that there is significant genetic variation in the five contiguous regional populations of the East Midlands. Some of this variation may be due to local geographical barriers, genetic drift and possibly the settlement patterns of Continental European invaders.