Abstract
We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits.
Highlights
Population definition, sample selection and choice of markers are crucial points in human population genetics studies, and the sampling strategy depends principally on the questions being asked
We studied mitochondrial DNA, since it has been extensively used as a molecular marker during the past 20 years, is maternally inherited, does not recombine and is in a haploid state; it is more sensitive than nuclear DNA to the effects of genetic drift and gene flow, and any discrepancy between the two sampling methods is expected to be enhanced
Estimates of genetic diversity (Table 2) obtained for the two sampling strategies were compatible with no occurrence of high levels of repeated haplotypes in the STD strategy, as could be expected
Summary
Population definition, sample selection and choice of markers are crucial points in human population genetics studies, and the sampling strategy depends principally on the questions being asked. The case-control experimental design is expected to be appropriate in surveys on homogeneous populations, whereas both false-positive and false-negative results may occur in heterogeneous or substructured populations, if cases and controls are not carefully sampled according to their origin. This scenario is likely to occur in an island like Sardinia, where the majority of the present population is distributed among 363 isolated villages (Siniscalco et al, 1999) which, while sharing common ancestry, might have diversified during many centuries of isolation. We showed there that the allele frequencies, and the genomic profile, remained constant even when only a subset of 20 individuals was analysed
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