Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes.
作者： Tze Hau Lam , Matthew Zirui Tay , Bei Wang , Ziwei Xiao , Ee Chee Ren
DOI: 10.1038/SREP16972
关键词:
摘要: Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, nature fine variations within their structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation two common Asian haplotypes: A33-B58-DR3 A2-B46-DR9. However, characterization phase-resolved revealed intra-CEH patterns variation uncovered 127 single nucleotide variants (SNVs) which missing from public databases. We further show that strong linkage disequilibrium typically confounds precise identification features can resolved using variants, evidenced rs3129063 rs448489, affect expression ZFP57, a gene important methylation epigenetic regulation. This study demonstrates an improved strategy used towards dissection
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