Population stratification of a common APOBEC gene deletion polymorphism.
The APOBEC3 gene family plays a role in innate cellular immunity inhibiting retroviral infection, hepatitis B virus propagation, and the retrotransposition of endogenous elements. We present a detailed sequence and population genetic analysis of a 29.5-kb common human deletion polymorphism that removes the APOBEC3B gene. We developed a PCR-based genotyping assay, characterized 1,277 human diversity samples, and found that the frequency of the deletion allele varies significantly among major continental groups (global FST = 0.2843). The deletion is rare in Africans and Europeans (frequency of 0.9% and 6%), more common in East Asians and Amerindians (36.9% and 57.7%), and almost fixed in Oceanic populations (92.9%). Despite a worldwide frequency of 22.5%, analysis of data from the International HapMap Project reveals that no single existing tag single nucleotide polymorphism may serve as a surrogate for the deletion variant, emphasizing that without careful analysis its phenotypic impact may be overlooked in association studies. Application of haplotype-based tests for selection revealed potential pitfalls in the direct application of existing methods to the analysis of genomic structural variation. These data emphasize the importance of directly genotyping structural variation in association studies and of accurately resolving variant breakpoints before proceeding with more detailed population-genetic analysis.
Kidd
Jeffrey M
JM
Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
Newman
Tera L
TL
Tuzun
Eray
E
Kaul
Rajinder
R
Eichler
Evan E
EE
D003564:Cytidine Deaminase / Q000235:genetics*; D017353:Gene Deletion; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D005843:Geography; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
D015778:Minor Histocompatibility Antigens; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase