A haplotype block model for fine mapping of quantitative trait loci regulating HIV-1 pathogenesis

Yun Zhu, Wei Hou, Rongling Wu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The dynamic change of human immunodeficiency virus type-1 (HIV-1) particles that cause AIDS displays considerable variation from patients to patients. It is likely that such variation in HIV-1 pathogenesis is correlated with the genetic architecture of hosts. Traditional genetic analysis of HIV-1 infection is based on various biochemical approaches, but it has been little successful because HIV-1 dynamics, as a complex trait, is under polygenic control and sensitive to enviromnental changes. Here, we present a novel model for integrating mathematical functions for HIV-1 dynamics that have been well constructed into a multivariate mixture model for genetic mapping. This integrative mapping model on the foundation of linkage disequilibrium (LD)-based haplotype block analysis provides unique power to precisely detect human quantitative trait loci (QTL) determining HIV-1 dynamics and facilitates positional cloning of target QTL. The model allows for a number of hypothesis tests for the effects of the dynamic QTL on the virion clearance rate, the infected cell life-span and the average viral generation time in vivo, all of which provide theoretical principles to guide the development of efficient gene therapy strategies.

Original languageEnglish (US)
Pages (from-to)227-234
Number of pages8
JournalJournal of Theoretical Medicine
Volume5
Issue number3-4
DOIs
StatePublished - Sep 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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