Journal of Theoretical Medicine
Volume 5 (2003), Issue 3-4, Pages 227-234

A Haplotype Block Model for Fine Mapping of Quantitative Trait Loci Regulating HIV-1 Pathogenesis

Department of Statistics, University of Florida, Gainesville, FL 32611, USA

Received 12 December 2003; Accepted 10 September 2004

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 environmental 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.