Document Detail

Observational, hypothesis-driven and genomics research strategies for analyzing inherited differences in responses to infectious diseases.
MedLine Citation:
PMID:  22543957     Owner:  NLM     Status:  In-Data-Review    
The first phase of research on genetic factors influencing susceptibility to infectious diseases was observational and descriptive. It began with the identification of children and adults with selective and non-selective immunodeficiencies. The types of infections to which these patients are susceptible provided evidence for the roles of T-cells, B-cells, leukocytes, and complement in controlling infectious diseases. Later the biochemical bases for these deficiencies were characterized. For example, an abnormal tyrosine kinase is associated with X-linked agammaglobulinemia, and lack of adenosine deaminase results in severe combined immunodeficiency. The second strategy for analyzing inherited resistance to disease was hypothesis-driven. Observations on the distribution of the sickle-cell gene suggested that heterozygotes might be resistant to P. falciparum malaria. That proposal has been confirmed repeatedly. Persons heterozygous for other hemoglobin mutations and those with glucose-6-phosphate dehydrogenase deficiency also have some degree of resistance to malaria. The third, modern phase of research on susceptibility to infectious diseases is genomic. This powerful approach facilitated characterization of the mutations responsible for most of the above-mentioned defects. Moreover, genomics strategies make analyses of susceptibility to infections possible even when these are under multifactorial genetic control, as exemplified by malaria. This is likely to be true for most infectious diseases, so the genomic approach is an important way forward.
A C Allison
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Publication Detail:
Type:  Journal Article     Date:  2008-09-05
Journal Detail:
Title:  Public health genomics     Volume:  12     ISSN:  1662-4246     ISO Abbreviation:  Public Health Genomics     Publication Date:  2009  
Date Detail:
Created Date:  2012-04-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101474167     Medline TA:  Public Health Genomics     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  41-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2008 S. Karger AG, Basel.
Alavita Pharmaceuticals Inc., Mountain View, Calif., USA.
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