Population-based gene discovery in the post-genomic era.

Area of Science:

• Genetics
• Medical Genetics
• Population Genetics

Background:

• Identifying genes for common diseases is complex.
• Many factors influence the choice of gene discovery methods.
• Linkage disequilibrium (LD) and genotypic relative risk (GRR) are key considerations.

Purpose of the Study:

• To review optimal approaches for discovering disease susceptibility genes.
• To discuss the impact of population type on gene discovery.
• To compare gene discovery in isolated versus outbred populations.

Main Methods:

• Review of genetic linkage and association study designs.
• Analysis of the effects of linkage disequilibrium (LD).
• Evaluation of genotypic relative risk (GRR) calculations.

Main Results:

• Isolated populations can offer advantages in gene discovery due to specific genetic characteristics.
• The choice between family-based and population-based designs impacts LD and GRR.
• Studying founder populations like Ashkenazi Jews versus outbred populations like Caucasians affects gene discovery outcomes.

Conclusions:

• Optimal gene discovery strategies must account for population-specific genetic factors.
• Understanding LD and GRR is crucial for accurate susceptibility gene identification.
• Population structure significantly influences the effectiveness of different genetic association and linkage studies.