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The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource

Sudden infant death syndrome (SIDS) is the unexpected death of an infant under one year of age that remains unexplained after a thorough investigation. Despite SIDS remaining a diagnosis of exclusion with an unexplained etiology, it is widely accepted that SIDS can be caused by environmental and/or...

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Autores principales: Johannsen, Emma B., Baughn, Linda B., Sharma, Neeraj, Zjacic, Nicolina, Pirooznia, Mehdi, Elhaik, Eran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913088/
https://www.ncbi.nlm.nih.gov/pubmed/33540853
http://dx.doi.org/10.3390/genes12020216
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author Johannsen, Emma B.
Baughn, Linda B.
Sharma, Neeraj
Zjacic, Nicolina
Pirooznia, Mehdi
Elhaik, Eran
author_facet Johannsen, Emma B.
Baughn, Linda B.
Sharma, Neeraj
Zjacic, Nicolina
Pirooznia, Mehdi
Elhaik, Eran
author_sort Johannsen, Emma B.
collection PubMed
description Sudden infant death syndrome (SIDS) is the unexpected death of an infant under one year of age that remains unexplained after a thorough investigation. Despite SIDS remaining a diagnosis of exclusion with an unexplained etiology, it is widely accepted that SIDS can be caused by environmental and/or biological factors, with multiple underlying candidate genes. However, the lack of biomarkers raises questions as to why genetic studies on SIDS to date are unable to provide a clearer understanding of the disease etiology. We sought to improve the identification of SIDS-associated genes by reviewing the SIDS genetic literature and objectively categorizing and scoring the reported genes based on the strength of evidence (from C1 (high) to C5 (low)). This was followed by analyses of function, associations between genes, the enrichment of gene ontology (GO) terms, and pathways and gender difference in tissue gene expression. We constructed a curated database for SIDS gene candidates consisting of 109 genes, 14 of which received a category 4 (C4) and 95 genes received the lowest category of C5. That none of the genes was classified into the higher categories indicates the low level of supporting evidence. We found that genes of both scoring categories show distinct networks and are highly diverse in function and involved in many GO terms and pathways, in agreement with the perception of SIDS as a heterogeneous syndrome. Genes of both scoring categories are part of the cardiac system, muscle, and ion channels, whereas immune-related functions showed enrichment for C4 genes. A limited association was found with neural development. Overall, inconsistent reports and missing metadata contribute to the ambiguity of genetic studies. Considering those parameters could help improve the identification of at-risk SIDS genes. However, the field is still far from offering a full-pledged genetic test to identify at-risk infants and is still hampered with methodological challenges and misunderstandings of the vulnerabilities of vital biological mechanisms.
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spelling pubmed-79130882021-02-28 The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource Johannsen, Emma B. Baughn, Linda B. Sharma, Neeraj Zjacic, Nicolina Pirooznia, Mehdi Elhaik, Eran Genes (Basel) Article Sudden infant death syndrome (SIDS) is the unexpected death of an infant under one year of age that remains unexplained after a thorough investigation. Despite SIDS remaining a diagnosis of exclusion with an unexplained etiology, it is widely accepted that SIDS can be caused by environmental and/or biological factors, with multiple underlying candidate genes. However, the lack of biomarkers raises questions as to why genetic studies on SIDS to date are unable to provide a clearer understanding of the disease etiology. We sought to improve the identification of SIDS-associated genes by reviewing the SIDS genetic literature and objectively categorizing and scoring the reported genes based on the strength of evidence (from C1 (high) to C5 (low)). This was followed by analyses of function, associations between genes, the enrichment of gene ontology (GO) terms, and pathways and gender difference in tissue gene expression. We constructed a curated database for SIDS gene candidates consisting of 109 genes, 14 of which received a category 4 (C4) and 95 genes received the lowest category of C5. That none of the genes was classified into the higher categories indicates the low level of supporting evidence. We found that genes of both scoring categories show distinct networks and are highly diverse in function and involved in many GO terms and pathways, in agreement with the perception of SIDS as a heterogeneous syndrome. Genes of both scoring categories are part of the cardiac system, muscle, and ion channels, whereas immune-related functions showed enrichment for C4 genes. A limited association was found with neural development. Overall, inconsistent reports and missing metadata contribute to the ambiguity of genetic studies. Considering those parameters could help improve the identification of at-risk SIDS genes. However, the field is still far from offering a full-pledged genetic test to identify at-risk infants and is still hampered with methodological challenges and misunderstandings of the vulnerabilities of vital biological mechanisms. MDPI 2021-02-02 /pmc/articles/PMC7913088/ /pubmed/33540853 http://dx.doi.org/10.3390/genes12020216 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Johannsen, Emma B.
Baughn, Linda B.
Sharma, Neeraj
Zjacic, Nicolina
Pirooznia, Mehdi
Elhaik, Eran
The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource
title The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource
title_full The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource
title_fullStr The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource
title_full_unstemmed The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource
title_short The Genetics of Sudden Infant Death Syndrome—Towards a Gene Reference Resource
title_sort genetics of sudden infant death syndrome—towards a gene reference resource
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913088/
https://www.ncbi.nlm.nih.gov/pubmed/33540853
http://dx.doi.org/10.3390/genes12020216
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