Population stratification of a common APOBEC gene deletion polymorphism

Area of Science:

• Genetics
• Human Population Genetics
• Immunology

Background:

• The APOBEC3 gene family is crucial for innate immunity, restricting viral infections and endogenous element retrotransposition.
• APOBEC3B is a key member of this family, though its function can be impacted by genetic variation.
• Understanding structural variations within this gene family is vital for human health and evolution.

Purpose of the Study:

• To perform a detailed population genetic analysis of a common 29.5-kb deletion polymorphism that eliminates the APOBEC3B gene.
• To investigate the frequency and distribution of this deletion across diverse human populations.
• To assess the utility of existing single nucleotide polymorphisms (SNPs) as surrogates for this structural variant in association studies.

Main Methods:

• Development of a Polymerase Chain Reaction (PCR)-based genotyping assay.
• Characterization of 1,277 human diversity samples to determine allele frequencies.
• Analysis of International HapMap Project data to evaluate tag SNP utility.

Main Results:

• The APOBEC3B deletion allele frequency varies significantly across continental groups (global FST = 0.2843).
• Frequencies range from rare in Africans (0.9%) and Europeans (6%) to common in East Asians (36.9%) and Amerindians (57.7%), and near fixation in Oceania (92.9%).
• No single tag SNP adequately represents this deletion variant in the International HapMap Project data.

Conclusions:

• Direct genotyping of structural variations like the APOBEC3B deletion is essential for accurate association studies.
• Existing tag SNPs are insufficient surrogates, potentially leading to overlooked phenotypic impacts.
• Accurate breakpoint resolution and direct genotyping are critical for robust population genetic analyses of structural variation.