02452nas a2200373   4500000000100000008004100001260001200042653000800054653002400062653001500086653001200101653003500113100001200148700001000160700001100170700000900181700000900190700000900199700001100208700001000219700001100229700000900240700001000249700001100259700001000270700001200280700001000292245010100302856008100403300001100484490000700495520156200502022001402064       2021                            d  c01/202110aMHC10acopy number variant10aimputation10aleprosy10aSingle nucleotide polymorphism1 aZhang R1 aCao L1 aChen W1 aGe H1 aHu X1 aLi Z1 aWang Y1 aFan W1 aYong L1 aYu Y1 aMao Y1 aZhen Q1 aLiu H1 aZhang F1 aSun L00aFine-Mapping of the Major Histocompatibility Complex Region Linked to Leprosy in Northern China.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716717/pdf/fgene-12-768259.pdf  a7682590 v123 a<p>Leprosy is a chronic infectious skin and neurological disease, and genetic background is considered to be one of the major factors of risk. The major histocompatibility complex (MHC) region not only affects susceptibility to leprosy but also its development and outcome. Given the complex traits of the MHC region, variants and the potential mechanism by which HLA influences leprosy development need to be further explored. We extracted previous genome-wide association study data from the Northern Han Chinese population to perform HLA fine-mapping. Using the 1,000 Genome Project Phase 3 dataset as the reference panel, single-nucleotide polymorphisms (SNP), insertion and deletion (INDEL) and copy number variant (CNV) imputation were carried out. HLA classical alleles and amino acids in the MHC region were imputed using the HAN-MHC database. Further stepwise regression analysis was conducted to analyze independent signals of variants related to leprosy. We identified four independent variants: esv3608598, rs7754498, rs3130781 and rs144388449. Among them, esv3608598 is a CNV and the first HLA CNV associated with leprosy risk. SNP annotation using RegulomeDB, HaploReg, and rVarBase showed that three SNPs are likely to affect the pathogenesis of leprosy. In summary, this is the first study to assess the association between HLA CNV and leprosy susceptibility in a Northern Han Chinese population. By fine mapping of the MHC region in this population, our findings provide evidence for the contribution of HLA to leprosy susceptibility.</p>
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