Hongzhi Cao:
MHC region and its related disease study

Date: 23-03-2015    Supervisor: Anders Krogh & Jun Wang

The major histocompatibility complex (MHC) is one of the most gene dense regions in the human genome and many disorders, including primary immune deficiencies, autoimmune conditions, infections, cancers and mental disorder have been found to be associated with this region. However, due to a high degree of polymorphisms within the MHC, the detection of variants in this region, and diagnostic HLA typing, still lacks a coherent, standardized, cost effective and high coverage protocol of clinical quality and reliability. And owing to marked linkage disequilibrium of MHC region, genes/mutations involved in the above diseases have not, with very few exceptions, been identified. Currently popular next-generation sequencing (NGS) technology, comprising massively parallel single-molecule sequencing, can generate billions of bases from amplified single DNA molecules within several days, holding great promise for achieving cost-effective and highthroughput and high accurate genotyping. Based on the NGS platform, by using delicately designed bioinformatics methods, we systematically developed new tools/methods, including high throughput HLA genotyping method – RCHSBT, targeted sequencing based SNV detection as well as HLA gene typing and large structural variation detection using optical mapping technic, to provide comprehensive and accurate information of the MHC region and apply them into disease causal mutation’s fine-mapping.