Domain altering SNPs in the human proteome and their impact on signaling pathways.

Single nucleotide polymorphisms (SNPs) constitute an important mode of genetic variations observed in the human genome. A small fraction of SNPs, about four thousand out of the ten million, has been associated with genetic disorders and complex diseases. The present study focuses on SNPs that fall o...

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Autores principales:	Yichuan Liu, Aydin Tozeren
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0bd048d52cb94e90851e1a194a335be7
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spelling	oai:doaj.org-article:0bd048d52cb94e90851e1a194a335be72021-11-18T06:34:49ZDomain altering SNPs in the human proteome and their impact on signaling pathways.1932-620310.1371/journal.pone.0012890https://doaj.org/article/0bd048d52cb94e90851e1a194a335be72010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20886114/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Single nucleotide polymorphisms (SNPs) constitute an important mode of genetic variations observed in the human genome. A small fraction of SNPs, about four thousand out of the ten million, has been associated with genetic disorders and complex diseases. The present study focuses on SNPs that fall on protein domains, 3D structures that facilitate connectivity of proteins in cell signaling and metabolic pathways. We scanned the human proteome using the PROSITE web tool and identified proteins with SNP containing domains. We showed that SNPs that fall on protein domains are highly statistically enriched among SNPs linked to hereditary disorders and complex diseases. Proteins whose domains are dramatically altered by the presence of an SNP are even more likely to be present among proteins linked to hereditary disorders. Proteins with domain-altering SNPs comprise highly connected nodes in cellular pathways such as the focal adhesion, the axon guidance pathway and the autoimmune disease pathways. Statistical enrichment of domain/motif signatures in interacting protein pairs indicates extensive loss of connectivity of cell signaling pathways due to domain-altering SNPs, potentially leading to hereditary disorders.Yichuan LiuAydin TozerenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e12890 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yichuan Liu Aydin Tozeren Domain altering SNPs in the human proteome and their impact on signaling pathways.
description	Single nucleotide polymorphisms (SNPs) constitute an important mode of genetic variations observed in the human genome. A small fraction of SNPs, about four thousand out of the ten million, has been associated with genetic disorders and complex diseases. The present study focuses on SNPs that fall on protein domains, 3D structures that facilitate connectivity of proteins in cell signaling and metabolic pathways. We scanned the human proteome using the PROSITE web tool and identified proteins with SNP containing domains. We showed that SNPs that fall on protein domains are highly statistically enriched among SNPs linked to hereditary disorders and complex diseases. Proteins whose domains are dramatically altered by the presence of an SNP are even more likely to be present among proteins linked to hereditary disorders. Proteins with domain-altering SNPs comprise highly connected nodes in cellular pathways such as the focal adhesion, the axon guidance pathway and the autoimmune disease pathways. Statistical enrichment of domain/motif signatures in interacting protein pairs indicates extensive loss of connectivity of cell signaling pathways due to domain-altering SNPs, potentially leading to hereditary disorders.
format	article
author	Yichuan Liu Aydin Tozeren
author_facet	Yichuan Liu Aydin Tozeren
author_sort	Yichuan Liu
title	Domain altering SNPs in the human proteome and their impact on signaling pathways.
title_short	Domain altering SNPs in the human proteome and their impact on signaling pathways.
title_full	Domain altering SNPs in the human proteome and their impact on signaling pathways.
title_fullStr	Domain altering SNPs in the human proteome and their impact on signaling pathways.
title_full_unstemmed	Domain altering SNPs in the human proteome and their impact on signaling pathways.
title_sort	domain altering snps in the human proteome and their impact on signaling pathways.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0bd048d52cb94e90851e1a194a335be7
work_keys_str_mv	AT yichuanliu domainalteringsnpsinthehumanproteomeandtheirimpactonsignalingpathways AT aydintozeren domainalteringsnpsinthehumanproteomeandtheirimpactonsignalingpathways
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Domain altering SNPs in the human proteome and their impact on signaling pathways.

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