![]() ![]() Non-additive allelic effects in the MHC, and epistatic effects between the MHC and other loci, can also complicate inference of the underlying haplotype structure and disease susceptibility variants. Another is that high and extensive LD in the locus makes it difficult to identify causal and independent loci. One fundamental challenge is that the MHC has many sequence and structural variations, which differ between populations and complicate haplotype inference. Several computational and empirical challenges complicate the mapping of MHC susceptibility variants. Finally, we discuss future directions for studying genetic variation in the MHC and how learning about the variation at this locus will aid understanding of disease pathogenesis. We also discuss the relationships between the MHC variants involved in both autoimmune and infectious diseases and offer insights into the MHC-associated immune responses underlying disease onset and pathogenesis. In this review, we discuss recent advances in mapping susceptibility variants in the MHC, using autoimmune and infectious diseases as examples (Boxes 2 and 3). ![]() However, the recent availability of dense genotyping platforms, such as the custom-made Illumina Infinium SNP chip (Immunochip), and of MHC reference panels has helped to fine-map the locus, improving our understanding of its disease associations and our ability to identify functional variants. The genetic structure of the MHC is characterized by high levels of linkage disequilibrium (LD) compared to the rest of the genome, which means there are technical challenges in identifying MHC single nucleotide polymorphisms (SNPs), alleles, and amino acids. In addition to autoimmune and inflammatory diseases, the MHC has recently been found to play a role in some neurological disorders, implicating autoimmune components in these diseases. Over the past 50 years, polymorphisms in the MHC locus have been shown to influence many critical biological traits and individuals’ susceptibility to complex, autoimmune, and infectious diseases (Boxes 2 and 3). Molecules encoded by this region are involved in antigen presentation, inflammation regulation, the complement system, and the innate and adaptive immune responses, indicating the MHC’s importance in immune-mediated, autoimmune, and infectious diseases. The major histocompatibility complex (MHC) locus, also known as the human leukocyte antigen (HLA) locus, spans around 4 Mbp on the short arm of chromosome 6 (6p21.3 Box 1). ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |