Relationship between copy number variation in innate immunity genes and infectious disease

Humans normally have two copies of every gene: one from their mother and one from their father. However, copy number variation, where different individuals have different numbers of the same gene, is more common than previously thought. This variation between people affects susceptibility to common diseases such as psoriasis. In this project, we will investigate copy number variation of three genes that are part of the body?s defence against bacteria and viruses. We will test if people with tuberculosis or AIDS have different numbers of these genes compared to healthy people. This will give clues on the importance of these genes involved in infection. It could also potentially identify drug targets for future work.

Recent work has suggested that copy number variation (CNV) is more common in the human genome than previously thought, and up to 12% of the genome may show CNV. Innate immunity genes are over-represented in regions in the genome that have been identified as showing CNV, therefore variation in gene dosage of innate immunity genes is likely to be a significant component of the total genetic variability in susceptibility to infectious disease. Our aim is to develop assays for three genomic regions that contains genes of the innate immune system and show CNV. They have been chosen as especially good candidates for involvement in HIV and tuberculosis infection. We will test how their variation affects susceptibility and severity of HIV-1 infection and tuberculosis by typing an African case-control cohort for CNV and selected sequence variation within the CNV. Any significant associations will be further tested on a further African and/or Chinese case-control cohort.