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cription and splicing, translation, and budding and release) varied among individuals. However, differences in transcription efficiency alone explained up to 80% of the total variance in viral production that was attributable to post-entry factors. The observation that transcription polymorphism has a weight comparable to that of entry variation should trigger a detailed analysis of genes participating in the activa- tion, transcriptional status, and transcriptional machinery of the cell. This observation is set in the context of current awareness of the role of variation in human gene expression underlying complex traits (Cox, 2004, Morley, 2004). The development of this well-characterized in-vitro system allowed us to use it as screening tool for HIV-1 restriction alleles (Bleiber, 2004). Susceptibility to HVI-1 is a complex trait compounded by unknown environmental and genetic factors pertaining to both the human host and the virus. To circumvent some of these difficulties we proposed a two-step strategy, in which distinct alleles in potential candidate genes are first assessed in vitro for their impact on viral replication, and subs- equently validated in vivo for their role in restricting HIV-1 infection. As a benchmark test we first tested 12 previously reported HIV-1 restriction alleles as well as single nucleotide polymorphisms in 10 ad- ditional candidate genes. This led to the identification of 3 new alleles associated with differences in progression of HIV-1 disease in the Swiss HIV Cohort Study. We estimate that the genetic effects of these markers might be responsible for lengthening or shortening the latency period to AIDS by up to 4.6 years. It is to facilitate this type of studies that we proposed the creation of the Genetics Project of the Swiss HIV Cohort Study (Telenti, 2004, Furrer, 2004). To complement the approach using CD4 T cells from blood donors, we are now using immortalized B lymphocytes from the Centre d’Etude du Polymorphisme Humain (CEPH) Utah pedigrees (Dausset, 1990). Here, quantitative traits can be mapped to chromosomal locations by genome scans (Schork, 2002, Jen, 2003, Cheung, 2003, Pastinen, 2004, Morley, 2004, Watters, 2004). While susceptibility to HIV-1 cannot be approached in vivo by linkage analyses, but only through association studies, the CEPH resource allows conventional linkage analysis for quan- 21