Genomics Select

The incredible leaps in technology that now make high-speed genome sequencing possible are revolutionizing the hunt for genes and genetic variations associated with disease. A stunning series of recent genome-wide association studies (GWAS) have identified new candidate genes for a number of common diseases including breast cancer, heart disease, diabetes type I and II, obesity, Crohn's disease, multiple sclerosis, glaucoma, and asthma. This Genomics Select highlights several of the most recent GWAS and also explores how a genome-wide approach can be used to address intriguing questions in cell and molecular biology. High-resolution GWAS enable at least half-a-million single nucleotide polymorphisms (SNPs, the most common form of genetic variants) to be compared between individuals with a particular disease and control subjects (case-control cohorts) or between family trios (affected child and both parents) and controls. Rigorous statistical analyses then identify those SNPs that are ''overtransmitted'' in affected individuals (transmission disequilibrium) and hence mark a particular gene or short genomic region as being associated with the presence or risk of a particular disease. In contrast to traditional candidate-gene approaches, such unbiased genome sweeps are more likely to identify new genes not suspected of association with a particular disease. Several of the most recent GWAS are highlighted here. In their study of more than 1000 patients with type I diabetes and their families , Hakonarson et al. (2007) identified significant association of three variants in the KIAA0350 gene on chromosome 16p13 with type I diabetes. This gene encodes a putative sugar-binding C-type lectin and is expressed predominantly in cells of the immune system including dendritic cells, B cells, and natural killer cells. The authors propose that the product of the KIAA0350 gene could be involved in antigen presentation, although it will take much more research to decipher how variations in this gene could contribute to the autoim-mune destruction of insulin-producing pancreatic b cells, the cause of type I diabetes. This work confirms KIAA0350's association with type I diabetes identified in a detailed analysis of two GWAS by Todd et al. (2007). The Todd et al. analysis also identified several other chromosomal loci associated with type I diabetes containing genes such as PTPN22 (encoding a T cell protein ty-rosine phosphatase) and CD226 (encoding a T cell costimulation factor), bringing to ten the number of genes implicated in this autoimmune disease. Tackling genetic risk factors for one of the leading causes of death, Samani et al. …