Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

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

Prevalence of lactase persistence and the performance of a non-invasive genetic test in adult Sardinian patients

Background &amp; aims Adult-type hypolactasia is a common problem in humans. In the clinical setting, the breath hydrogen test is frequently used to measure lactose nonabsorption; however, false results can occur. The prevalence of genetic lactase persistence in Sardinia and the performance of a new non-invasive genetic test based on the presence of C/T-13910 polymorphism were evaluated. Methods Saliva was collected from adult patients undergoing breath hydrogen test and from a control group of healthy subjects. DNA was analyzed for C/T-13910 and four additional mutations nearby. Results One hundred and twenty patients and 120 controls were enrolled. In the patient group, the frequency of the C/C-13910 (homozygous genotype for lactase non-persistence) was 89.2%; the C/T (heterozygosity for lactase persistence) was 10.8%; and the T/T (homozygous for lactase persistence) was 0. The frequency for C/C, C/T, T/T was 78.3%, 21.7%, and 0, respectively, in the control group. The sensitivity, specificity and accuracy of the breath hydrogen test compared to the genetic test were 86.1%, 92.3%, and 87.5%, respectively. The concordance of the results of the two tests was highly significant (p &lt; 0.0001). Conclusions Mutants for lactase persistence are very uncommon in Sardinia. Simplicity of genotyping −13910 C/T to assess the lactase non-persistence should make this method suitable for routine clinical testing when lactose malabsorption is suspected