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Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis

Unraveling of the HLA-related immunogenetic basis of several immune disorders is complex due to the extensive HLA polymorphism and strong linkage-disequilibrium between HLA loci. A lack of in phase sequence information, a relative deficiency of high resolution genotyping including non-coding regions...

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Autores principales: Kishore, Amit, Petrek, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210504/
https://www.ncbi.nlm.nih.gov/pubmed/30410504
http://dx.doi.org/10.3389/fgene.2018.00503
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author Kishore, Amit
Petrek, Martin
author_facet Kishore, Amit
Petrek, Martin
author_sort Kishore, Amit
collection PubMed
description Unraveling of the HLA-related immunogenetic basis of several immune disorders is complex due to the extensive HLA polymorphism and strong linkage-disequilibrium between HLA loci. A lack of in phase sequence information, a relative deficiency of high resolution genotyping including non-coding regions and ambiguous haplotype assignment make it difficult to compare findings across association studies and to attribute a causal role to specific HLA alleles/haplotypes in disease susceptibility and modification of disease phenotypes. Earlier, historical antibody and DNA-based methods of HLA typing, primarily of low resolution at antigen/alellic group levels, yielded “indicative” findings which were partially improved by high-resolution DNA-based typing. Only recently, next-generation sequencing (NGS) approaches based on deep-sequencing of the complete HLA genes combined with bioinformatics tools began to provide the access to complete information at an allelic level. Analyzing HLA with NGS approaches, therefore, promises to provide further insight in the etiopathogenesis of several immune disorders in which HLA associations have been implicated. These range from coeliac disease and rheumatological conditions to even more complex disorders, such as type-1 diabetes, systemic lupus erythematosus and sarcoidosis. A systemic disease of unknown etiology, sarcoidosis has previously been associated with numerous HLA variants and also other gene polymorphisms, often in linkage with the HLA region. To date, the biological significance of these associations has only partially been defined. Therefore, more precise assignments of HLA alleles/haplotypes using NGS approaches could help to elucidate the exact role of HLA variation in the multifaceted etiopathogenesis of sarcoidosis, including epigenetic mechanisms. NGS-based HLA analyses may be also relevant for defining variable clinical phenotypes and for predicting the disease course or the response to current/plausible novel therapies.
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spelling pubmed-62105042018-11-08 Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis Kishore, Amit Petrek, Martin Front Genet Genetics Unraveling of the HLA-related immunogenetic basis of several immune disorders is complex due to the extensive HLA polymorphism and strong linkage-disequilibrium between HLA loci. A lack of in phase sequence information, a relative deficiency of high resolution genotyping including non-coding regions and ambiguous haplotype assignment make it difficult to compare findings across association studies and to attribute a causal role to specific HLA alleles/haplotypes in disease susceptibility and modification of disease phenotypes. Earlier, historical antibody and DNA-based methods of HLA typing, primarily of low resolution at antigen/alellic group levels, yielded “indicative” findings which were partially improved by high-resolution DNA-based typing. Only recently, next-generation sequencing (NGS) approaches based on deep-sequencing of the complete HLA genes combined with bioinformatics tools began to provide the access to complete information at an allelic level. Analyzing HLA with NGS approaches, therefore, promises to provide further insight in the etiopathogenesis of several immune disorders in which HLA associations have been implicated. These range from coeliac disease and rheumatological conditions to even more complex disorders, such as type-1 diabetes, systemic lupus erythematosus and sarcoidosis. A systemic disease of unknown etiology, sarcoidosis has previously been associated with numerous HLA variants and also other gene polymorphisms, often in linkage with the HLA region. To date, the biological significance of these associations has only partially been defined. Therefore, more precise assignments of HLA alleles/haplotypes using NGS approaches could help to elucidate the exact role of HLA variation in the multifaceted etiopathogenesis of sarcoidosis, including epigenetic mechanisms. NGS-based HLA analyses may be also relevant for defining variable clinical phenotypes and for predicting the disease course or the response to current/plausible novel therapies. Frontiers Media S.A. 2018-10-25 /pmc/articles/PMC6210504/ /pubmed/30410504 http://dx.doi.org/10.3389/fgene.2018.00503 Text en Copyright © 2018 Kishore and Petrek. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Kishore, Amit
Petrek, Martin
Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis
title Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis
title_full Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis
title_fullStr Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis
title_full_unstemmed Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis
title_short Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis
title_sort next-generation sequencing based hla typing: deciphering immunogenetic aspects of sarcoidosis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210504/
https://www.ncbi.nlm.nih.gov/pubmed/30410504
http://dx.doi.org/10.3389/fgene.2018.00503
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