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Host genomics in infectious diseases.

ABSTRACT: 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.

SUBMITTER: Loeb M

PROVIDER: S-EPMC3848513 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Host genomics in infectious diseases.

Loeb Mark M

Infection & chemotherapy 20130927 3

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 stu ...[more]

PMID: 24396626

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Project description:Environmentally growing pathogens present an increasing threat for human health, wildlife and food production. Treating the hosts with antibiotics or parasitic bacteriophages fail to eliminate diseases that grow also in the outside-host environment. However, bacteriophages could be utilized to suppress the pathogen population sizes in the outside-host environment in order to prevent disease outbreaks. Here, we introduce a novel epidemiological model to assess how the phage infections of the bacterial pathogens affect epidemiological dynamics of the environmentally growing pathogens. We assess whether the phage therapy in the outside-host environment could be utilized as a biological control method against these diseases. We also consider how phage-resistant competitors affect the outcome, a common problem in phage therapy. The models give predictions for the scenarios where the outside-host phage therapy will work and where it will fail to control the disease. Parameterization of the model is based on the fish columnaris disease that causes significant economic losses to aquaculture worldwide. However, the model is also suitable for other environmentally growing bacterial diseases.Transmission rates of the phage determine the success of infectious disease control, with high-transmission phage enabling the recovery of the host population that would in the absence of the phage go asymptotically extinct due to the disease. In the presence of outside-host bacterial competition between the pathogen and phage-resistant strain, the trade-off between the pathogen infectivity and the phage resistance determines phage therapy outcome from stable coexistence to local host extinction.We propose that the success of phage therapy strongly depends on the underlying biology, such as the strength of trade-off between the pathogen infectivity and the phage-resistance, as well as on the rate that the phages infect the bacteria. Our results indicate that phage therapy can fail if there are phage-resistant bacteria and the trade-off between pathogen infectivity and phage resistance does not completely inhibit the pathogen infectivity. Also, the rate that the phages infect the bacteria should be sufficiently high for phage-therapy to succeed.

Dataset Information

Host genomics in infectious diseases.

Publications

Host genomics in infectious diseases.

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