Extent of linkage disequilibrium in a Sardinian sub-isolate: sampling and methodological considerations

Area of Science:

• Population genetics
• Genetic mapping

Background:

• Linkage disequilibrium (LD) is crucial for genetic mapping studies.
• LD patterns are population-specific due to demographic history.

Purpose of the Study:

• To assess the extent of LD in a Sardinian sub-isolate.
• To evaluate the impact of sample size and data quality on LD estimates.

Main Methods:

• Genotyping of 22 polymorphic markers on chromosome 19 in 775 individuals.
• Analysis of LD using D' and allelic association significance.
• Resampling techniques to assess sample size effects.
• Evaluation of pedigree depth and allele grouping impacts.

Main Results:

• High LD levels observed, extending to 8 cM (D') and 11 cM (significance).
• Small sample sizes (26 diplotypes) led to overestimations of D' (2x) and its variance (16x).
• Pedigree depth and allele grouping influenced D' estimates.

Conclusions:

• LD estimates were robust across different analytical methods.
• Characterizing LD requires large sample sizes (>=200 unrelated individuals) due to high sampling variance.
• Findings inform experimental design for LD-based genetic mapping.