HLA Immune Function Genes in Autism

Abstract

The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

Figure 1

Gene map of the human leukocyte antigen (HLA) region. The major histocompatibility complex (MHC) gene map corresponds to the genomic coordinates of 29677984 (GABBR I) to 33485635 (KIFC1) in the human genome build 36.3 of the National Center for Biotechnology Information (NCBI) map viewer. The regions separated by arrows show the HLA subregions such as extended class I, classical class I, class III, classical class II, and extended class II regions from telomere (left and top side) to centromere (right and bottom side). White, gray, striped and black boxes show expressed genes, gene candidates, noncoding genes and pseudogenes, respectively. The location of the alpha, beta, and kappa blocks containing the cluster of duplicated HLA class I genes in the class I region are indicated. (Reprinted with permission from the Journal of Human Genetics [87].)