TY - JOUR
T1 - A haplotype block model for fine mapping of quantitative trait loci regulating HIV-1 pathogenesis
AU - Zhu, Yun
AU - Hou, Wei
AU - Wu, Rongling
PY - 2003/9
Y1 - 2003/9
N2 - 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.
AB - 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.
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U2 - 10.1080/10273660412331319486
DO - 10.1080/10273660412331319486
M3 - Article
AN - SCOPUS:10944233207
SN - 1027-3662
VL - 5
SP - 227
EP - 234
JO - Journal of Theoretical Medicine
JF - Journal of Theoretical Medicine
IS - 3-4
ER -