Originally published as Genetics Published Articles Ahead of Print on August 30, 2008.

Genetics, Vol. 180, 445-457, September 2008, Copyright © 2008
doi:10.1534/genetics.108.090340

Human Endogenous Retrovirus (HERVK9) Structural Polymorphism With Haplotypic HLA-A Allelic Associations

Jerzy K. Kulski*,1, Atsuko Shigenari{dagger}, Takashi Shiina{dagger}, Masao Ota{ddagger}, Kazuyoshi Hosomichi{dagger}, Ian James§ and Hidetoshi Inoko{dagger}

* Centre for Forensic Science, The University of Western Australia, Nedlands, 6009 Western Australia, Australia, {dagger} Division of Molecular Life Science, Department of Genetic Information, School of Medicine, Tokai University, Isehara, Kanagawa 259-1193, Japan, {ddagger} Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan and § Centre for Clinical Immunology and Biomedical Statistics, Murdoch University and Royal Perth Hospital, Murdoch, 6150 Western Australia, Australia

1 Corresponding author: Centre for Forensic Science, The University of Western Australia, M420, 35 Stirling Highway, Crawley, Western Australia 6008, Australia.
E-mail: kulski{at}mac.com

The frequency and HLA-A allelic associations of a HERVK9 DNA structural polymorphism located in close proximity to the highly polymorphic HLA-A gene within the major histocompatibility complex (MHC) genomic region were determined in Japanese, African Americans, and Australian Caucasians to better understand its human population evolutionary history. The HERVK9 insertion or deletion was detected as a 3' LTR or a solo LTR, respectively, by separate PCR assays. The average insertion frequency of the HERVK9.HG was significantly different (P < 1.083e–6) between the Japanese (0.59) and the African Americans (0.34) or Australian Caucasians (0.37). LD analysis predicted a highly significant (P < 1.0e–5) linkage between the HLA-A and HERVK9 alleles, probably as a result of hitchhiking (linkage). Evolutionary time estimates of the solo, 5' and 3' LTR nucleotide sequence divergences suggest that the HERVK9 was inserted 17.3 MYA with the first structural deletion occurring 15.1 MYA. The LTR/HLA-A haplotypes appear to have been formed mostly during the past 3.9 MY. The HERVK9 insertion and deletion, detected by a simple and economical PCR method, is an informative genetic and evolutionary marker for the study of HLA-A haplotype variations, human migration, the origins of contemporary populations, and the possibility of disease associations.