Coherent somatic mutation in autoimmune disease.

<h4>Background</h4>Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and dele...

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Autor principal:	Kenneth Andrew Ross
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae1e64c871ee4c7daeda51dd5a3e3330
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spelling	oai:doaj.org-article:ae1e64c871ee4c7daeda51dd5a3e33302021-11-25T06:09:50ZCoherent somatic mutation in autoimmune disease.1932-620310.1371/journal.pone.0101093https://doaj.org/article/ae1e64c871ee4c7daeda51dd5a3e33302014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24988487/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation.<h4>Results</h4>Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (p<3.0x10(-7)). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed.<h4>Conclusions</h4>The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases.Kenneth Andrew RossPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101093 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenneth Andrew Ross Coherent somatic mutation in autoimmune disease.
description	<h4>Background</h4>Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation.<h4>Results</h4>Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (p<3.0x10(-7)). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed.<h4>Conclusions</h4>The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases.
format	article
author	Kenneth Andrew Ross
author_facet	Kenneth Andrew Ross
author_sort	Kenneth Andrew Ross
title	Coherent somatic mutation in autoimmune disease.
title_short	Coherent somatic mutation in autoimmune disease.
title_full	Coherent somatic mutation in autoimmune disease.
title_fullStr	Coherent somatic mutation in autoimmune disease.
title_full_unstemmed	Coherent somatic mutation in autoimmune disease.
title_sort	coherent somatic mutation in autoimmune disease.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ae1e64c871ee4c7daeda51dd5a3e3330
work_keys_str_mv	AT kennethandrewross coherentsomaticmutationinautoimmunedisease
_version_	1718414123901911040

Coherent somatic mutation in autoimmune disease.

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