期刊
HUMAN IMMUNOLOGY
卷 80, 期 1, 页码 67-78出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2018.10.002
关键词
Linkage disequilibrium; Phase; Phylogeny; Linage-specific expression; HIV-AIDS; Hepatitis B; Crohn's disease; Unrelated donor hematopoietic cell transplantation; Graft-versus-host disease
类别
资金
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- NIH, Frederick National Laboratory Center for Cancer Research
- National Institutes of Health, USA [AI069197, CA100019, CA218285, CA231838]
- NATIONAL CANCER INSTITUTE [R01CA231838, R01CA100019, R01CA218285] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI069197] Funding Source: NIH RePORTER
The MHC continues to have the most disease-associations compared to other regions of the human genome, even in the genome-wide association study (GWAS) and single nucleotide polymorphism (SNP) era. Analysis of non coding variation and their impact on the level of expression of HLA allotypes has shed new light on the potential mechanisms underlying HLA disease associations and alloreactivity in transplantation. Next-generation sequencing (NGS) technology has the capability of delineating the phase of variants in the HLA antigen-recognition site (ARS) with non-coding regulatory polymorphisms. These relationships are critical for understanding the qualitative and quantitative implications of HLA gene diversity. This article summarizes current understanding of non-coding region variation of HLA loci, the consequences of regulatory variation on HLA expression, the role for evolution in shaping lineage-specific expression, and the impact of HLA expression on disease susceptibility and transplantation outcomes. A role for phased sequencing methods for the MHC, and perspectives for future directions in basic and applied immunogenetic studies of the MHC are presented.
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