The human Major Histocompatibility Complex as a paradigm in genomics research

Abstract

Since its discovery more than 50 years ago, the human Major Histocompatibility Complex (MHC) on chromosome 6p21.3 has been at the forefront of human genetic research. Here, we review from a historical perspective the major advances in our understanding of the nature and consequences of genetic variation which have involved the MHC, as well as highlighting likely future directions. As a consequence of its particular genomic structure, its remarkable polymorphism and its early implication in numerous diseases, the MHC has been considered as a model region for genomics, being the first substantial region to be sequenced and establishing fundamental concepts of linkage disequilibrium, haplotypic structure and meiotic recombination. Recently, the MHC became the first genomic region to be entirely re-sequenced for common haplotypes, while studies mapping gene expression phenotypes across the genome have strongly implicated variation in the MHC. This review shows how the MHC continues to provide new insights and remains in the vanguard of contemporary research in human genomics.

Figure 1

Timeline of research in the MHC and human genome

Figure 2. Genetic variation in the MHC

Number of polymorphisms per 10 kb across the MHC. Polymorphisms were extracted from dbSNP build 129, microsatellites from dbMHC, copy number variants and indels from the Database of Genomic Variants version 6, and segmental duplications of more than 1 kb from the ucsc table browser [174].