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Pathog Dis. 2014 Jul;71(2):234-48. doi: 10.1111/2049-632X.12160. Epub 2014 Mar 11.

Mapping complex traits using families of recombinant inbred strains: an overview and example of mapping susceptibility to Candida albicans induced illness phenotypes.

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1
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA.

Abstract

This overview and data-based example indicate how large families of recombinant inbred (RI) strains can be used to identify genetic loci and genes that underlie complex phenotypic differences among inbred mice. The RI approach requires no a priori expectations or assumptions about mechanisms that influence the phenotype, other than that variability is partly heritable. RI strains, which are produced by inbreeding the F2 progeny of two parental strains for at least 20 generations, have two major advantages. First, numerous subjects with identical genotypes can be analyzed to determine the average phenotype associated with that genotype, and second, it becomes practical to systematically accumulate large genome and phenome data sets for entire RI families, including sequence data, transcriptomes for many organs, and cell types and extensive data on gene-by-pathogen interactions. This enables the construction of far more sophisticated models of disease cause and progression. To illustrate the use of the systems genetics approach to infectious disease, we designed a simple study using three complementary families of RI strains (CXB, BXD, and AXB/BXA) that are differentially susceptible to intravenous challenge with the yeast Candida albicans.

KEYWORDS:

QTL; infection; inflammation; locomotor activity; temperature

PMID:
24535895
DOI:
10.1111/2049-632X.12160
[Indexed for MEDLINE]
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