Catriona M Macfarlane1, Richard M Badge2. 1. Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK. cm182@leicester.ac.uk. 2. Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK. rmb19@leicester.ac.uk.
Abstract
BACKGROUND: To date, the human population census of proviruses of the Betaretrovirus-like human endogenous retroviral (HERV-K) (HML-2) family has been compiled from a limited number of complete genomes, making it certain that rare polymorphic loci are under-represented and are yet to be described. RESULTS: Here we describe a suppression PCR-based method called genome-wide amplification of proviral sequences (GAPS) that selectively amplifies DNA fragments containing the termini of HERV-K(HML-2) proviral sequences and their flanking genomic sequences. We analysed the HERV-K(HML-2) proviral content of 101 unrelated humans, 4 common chimpanzees and three centre d'etude du polymorphisme humain (CEPH) pedigrees (44 individuals). The technique isolated HERV-K(HML-2) proviruses that had integrated in the genomes of the great apes throughout their divergence and included evolutionarily young elements still unfixed for presence/absence. CONCLUSIONS: By examining the HERV-K(HML-2) proviral content of 145 humans we detected a new insertionally polymorphic Type I HERV-K(HML-2) provirus. We also observed provirus versus solo long terminal repeat (LTR) polymorphism within humans at a previously unreported, but ancient, locus. Finally, we report two novel chimpanzee specific proviruses, one of which is dimorphic for a provirus versus solo LTR. Thus GAPS enables the isolation of uncharacterised HERV-K(HML-2) proviral sequences and provides a direct means to assess inter-individual genetic variation associated with HERV-K(HML-2) proviruses.
BACKGROUND: To date, the human population census of proviruses of the Betaretrovirus-like human endogenous retroviral (HERV-K) (HML-2) family has been compiled from a limited number of complete genomes, making it certain that rare polymorphic loci are under-represented and are yet to be described. RESULTS: Here we describe a suppression PCR-based method called genome-wide amplification of proviral sequences (GAPS) that selectively amplifies DNA fragments containing the termini of HERV-K(HML-2) proviral sequences and their flanking genomic sequences. We analysed the HERV-K(HML-2) proviral content of 101 unrelated humans, 4 common chimpanzees and three centre d'etude du polymorphisme humain (CEPH) pedigrees (44 individuals). The technique isolated HERV-K(HML-2) proviruses that had integrated in the genomes of the great apes throughout their divergence and included evolutionarily young elements still unfixed for presence/absence. CONCLUSIONS: By examining the HERV-K(HML-2) proviral content of 145 humans we detected a new insertionally polymorphic Type I HERV-K(HML-2) provirus. We also observed provirus versus solo long terminal repeat (LTR) polymorphism within humans at a previously unreported, but ancient, locus. Finally, we report two novel chimpanzee specific proviruses, one of which is dimorphic for a provirus versus solo LTR. Thus GAPS enables the isolation of uncharacterised HERV-K(HML-2) proviral sequences and provides a direct means to assess inter-individual genetic variation associated with HERV-K(HML-2) proviruses.
Authors: Joseph R Holloway; Zachary H Williams; Michael M Freeman; Uriel Bulow; John M Coffin Journal: Proc Natl Acad Sci U S A Date: 2019-01-04 Impact factor: 11.205
Authors: Mark H Kaplan; Mark Kaminski; Judith M Estes; Scott D Gitlin; Joseph Zahn; James T Elder; Trilokraj Tejasvi; Elizabeth Gensterblum; Amr H Sawalha; Joseph Patrick McGowan; Michael H Dosik; Haner Direskeneli; Guher Saruhan Direskeneli; Sally N Adebamowo; Clement A Adebamowo; Mohammad Sajadi; Rafael Contreras-Galindo Journal: BMC Med Genomics Date: 2019-05-02 Impact factor: 3.063
Authors: Witold Tatkiewicz; James Dickie; Franchesca Bedford; Alexander Jones; Mark Atkin; Michele Kiernan; Emmanuel Atangana Maze; Bora Agit; Garry Farnham; Alexander Kanapin; Robert Belshaw Journal: Mob DNA Date: 2020-02-07
Authors: Bei Xue; Tiansheng Zeng; Lisha Jia; Dongsheng Yang; Stanley L Lin; Leonardo A Sechi; David J Kelvin Journal: Retrovirology Date: 2020-05-06 Impact factor: 4.602