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Host Genomics in Infectious Diseases

Understanding mechanisms by which genetic variants predispose to complications of infectious diseases can lead to important benefits including the development of biomarkers to prioritize vaccination or prophylactic therapy. Family studies, candidate genes in animal models, and the absence of well-de...

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Autor principal: Loeb, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Infectious Diseases and Korean Society for Chemotherapy 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848513/
https://www.ncbi.nlm.nih.gov/pubmed/24396626
http://dx.doi.org/10.3947/ic.2013.45.3.253
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author Loeb, Mark
author_facet Loeb, Mark
author_sort Loeb, Mark
collection PubMed
description Understanding mechanisms by which genetic variants predispose to complications of infectious diseases can lead to important benefits including the development of biomarkers to prioritize vaccination or prophylactic therapy. Family studies, candidate genes in animal models, and the absence of well-defined risks where the complications are rare all can point to genetic predisposition. The most common approach to assessing genetic risk is to conduct an association study, which is a case control study using either a candidate gene approach or a genome wide approach. Although candidate gene variants may focus on potentially causal variants, because other variants across the genome are not tested these studies frequently cannot be replicated. Genome wide association studies need a sizable sample and usually do not identify causal variants but variants which may be in linkage disequilibrium to the actual causal variant. There are many pitfalls that can lead to bias in such studies, including misclassification of cases and controls, use of improper phenotypes, and genotyping errors. These studies have been limited to common genes and rare variants may not be detected. As the use of next generation sequencing becomes more common, it can be anticipated that more variants will be confirmed. The purpose of this review article is to address the issue of genomics in infectious diseases with an emphasis on the host. Although there are a plentitude of studies that focus on the molecular characteristics of pathogens, there are far fewer studies that address the role of human genetics in the predisposition to infection or more commonly its complications. This paper will review both the approaches used to study host genetics in humans and the pitfalls associated with some of these methods. The focus will be on human disease and therefore discussion of the use of animal models will be limited to those where there are genes that have been replicated in humans. The paper will focus on common genetic variants that account for complex traits such as infectious diseases using examples from flaviviruses.
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spelling pubmed-38485132014-01-06 Host Genomics in Infectious Diseases Loeb, Mark Infect Chemother Review Article Understanding mechanisms by which genetic variants predispose to complications of infectious diseases can lead to important benefits including the development of biomarkers to prioritize vaccination or prophylactic therapy. Family studies, candidate genes in animal models, and the absence of well-defined risks where the complications are rare all can point to genetic predisposition. The most common approach to assessing genetic risk is to conduct an association study, which is a case control study using either a candidate gene approach or a genome wide approach. Although candidate gene variants may focus on potentially causal variants, because other variants across the genome are not tested these studies frequently cannot be replicated. Genome wide association studies need a sizable sample and usually do not identify causal variants but variants which may be in linkage disequilibrium to the actual causal variant. There are many pitfalls that can lead to bias in such studies, including misclassification of cases and controls, use of improper phenotypes, and genotyping errors. These studies have been limited to common genes and rare variants may not be detected. As the use of next generation sequencing becomes more common, it can be anticipated that more variants will be confirmed. The purpose of this review article is to address the issue of genomics in infectious diseases with an emphasis on the host. Although there are a plentitude of studies that focus on the molecular characteristics of pathogens, there are far fewer studies that address the role of human genetics in the predisposition to infection or more commonly its complications. This paper will review both the approaches used to study host genetics in humans and the pitfalls associated with some of these methods. The focus will be on human disease and therefore discussion of the use of animal models will be limited to those where there are genes that have been replicated in humans. The paper will focus on common genetic variants that account for complex traits such as infectious diseases using examples from flaviviruses. The Korean Society of Infectious Diseases and Korean Society for Chemotherapy 2013-09 2013-09-27 /pmc/articles/PMC3848513/ /pubmed/24396626 http://dx.doi.org/10.3947/ic.2013.45.3.253 Text en Copyright © 2013 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Loeb, Mark
Host Genomics in Infectious Diseases
title Host Genomics in Infectious Diseases
title_full Host Genomics in Infectious Diseases
title_fullStr Host Genomics in Infectious Diseases
title_full_unstemmed Host Genomics in Infectious Diseases
title_short Host Genomics in Infectious Diseases
title_sort host genomics in infectious diseases
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848513/
https://www.ncbi.nlm.nih.gov/pubmed/24396626
http://dx.doi.org/10.3947/ic.2013.45.3.253
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