Single Nucleotide Polymorphism Blocks and Haplotypes: Human MHC Block Diversity

Abstract

We describe genetically fixed segments of DNA within the major histocompatibility complex (MHC) extending to 3.2 Mb of DNA from HLA-A to HLA-DPB1. These are variable sized DNA fragments that vary in frequency in different ethnicities or races. Within the region, one 1.5-Mb block is relatively frequent, the DNA conserved extended haplotypes (CEHs). These span from HLA-Cw, B to HLA-DRB1, DQB1 and include the polymorphisms of complement genes (complotypes) and TNF (tumor necrosis factor genes). This segment is informative for mapping disease susceptibility, immune responses, and allotransplantation matching. Other chromosomal regions (paralogous) have conserved genes, including those genetically related to those of the MHC, which also form DNA blocks that could be involved in immune functions and show disease association. DNA blocks can be used to measure human diversity. For example, the aggregate frequency of DNA blocks (ABF), determine the degree of genetic diversity in different populations; Africans, Asians, and Hispanics have higher genetic diversity than Caucasian Americans. The use of single nucleotide polymorphisms (SNPs) to determine DNA blocks (by measurement of linkage disequilibrium (LD)) is limited when ignoring the well-documented variability of frequency and size of DNA blocks among different populations.