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Accurately measuring recombination between closely related HIV-1 genomes

Schlub, Timothy E., Smyth, Redmond P., Grimm, Andrew J., Mak, Johnson and Davenport, Miles P. 2010, Accurately measuring recombination between closely related HIV-1 genomes, PLoS computational biology, vol. 6, no. 4, pp. 1-11, doi: 10.1371/journal.pcbi.1000766.

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Title Accurately measuring recombination between closely related HIV-1 genomes
Author(s) Schlub, Timothy E.
Smyth, Redmond P.
Grimm, Andrew J.
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Davenport, Miles P.
Journal name PLoS computational biology
Volume number 6
Issue number 4
Start page 1
End page 11
Total pages 11
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2010-04
ISSN 1553-734X
Keyword(s) algorithms
cell lines
codon
genetic markers
viral genome
HIV-1
humans
models
genetic
poisson distribution
genetic recombination
genetic templates
Summary Retroviral recombination is thought to play an important role in the generation of immune escape and multiple drug resistance by shuffling pre-existing mutations in the viral population. Current estimates of HIV-1 recombination rates are derived from measurements within reporter gene sequences or genetically divergent HIV sequences. These measurements do not mimic the recombination occurring in vivo, between closely related genomes. Additionally, the methods used to measure recombination make a variety of assumptions about the underlying process, and often fail to account adequately for issues such as co-infection of cells or the possibility of multiple template switches between recombination sites. We have developed a HIV-1 marker system by making a small number of codon modifications in gag which allow recombination to be measured over various lengths between closely related viral genomes. We have developed statistical tools to measure recombination rates that can compensate for the possibility of multiple template switches. Our results show that when multiple template switches are ignored the error is substantial, particularly when recombination rates are high, or the genomic distance is large. We demonstrate that this system is applicable to other studies to accurately measure the recombination rate and show that recombination does not occur randomly within the HIV genome.
Language eng
DOI 10.1371/journal.pcbi.1000766
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2010, Public Library of Science
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047590

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.