Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation

Advances in Immunology
Takehiko SasazukiY Morishima

Abstract

The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases. The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves' disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles. Their epistatic interactions in controlling the development of these diseases are shown. Four susceptible and one resistant HLA alleles are shared by GD and HT. Two HLA alleles associated with GD or HT control the titers of autoantibodies to thyroid antigens. All these observations led us to propose a new model for the development of GD and HT. Hematopoietic stem cell t...Continue Reading

Citations

Jun 15, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Effie W PetersdorfTao Wang
Sep 21, 2019·Human Genetics·Mohit K MidhaKuo-Ping Chiu
Feb 6, 2020·Annual Review of Immunology·Shimon SakaguchiNaganari Ohkura
Dec 6, 2017·Molecular Medicine Reports·Ting-Jun JiangPeng Fu
Aug 7, 2019·Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society for Pediatric Endocrinology·Tomohiro HoriToshiyuki Fukao
Apr 10, 2020·Endocrinology·Liang YinJie Shen

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