NDLI: Collaborative Cross mice and their power to map host susceptibility to Aspergillus fumigatus infection

Content Provider	PubMed Central
Author	Durrant, Caroline Hanna, Tayem Yalcin, Binnaz James, Cleak Leo, Goodstadt Villena, Fernando Pardo-manuel De Mott, Richard Iraqi, Fuad A.
Copyright Year	2011
Abstract	The Collaborative Cross (CC) is a genetic reference panel of recombinant inbred lines of mice, designed for the dissection of complex traits and gene networks. Each line is independently descended from eight genetically diverse founder strains such that the genomes of the CC lines, once fully inbred, are fine-grained homozygous mosaics of the founder haplotypes. We present an analysis of 120 CC lines, from a cohort of the CC bred at Tel Aviv University in collaboration with the University of Oxford, which at the time of this study were between the sixth and 12th generations of inbreeding and substantially homozygous at 170,000 SNPs. We show how CC genomes decompose into mosaics, and we identify loci that carry a deficiency or excess of a founder, many being deficient for the wild-derived strains WSB/EiJ and PWK/PhJ. We phenotyped 371 mice from 66 CC lines for a susceptibility to Aspergillus fumigatus infection. The survival time after infection varied significantly between CC lines. Quantitative trait locus (QTL) mapping identified genome-wide significant QTLs on chromosomes 2, 3, 8, 10 (two QTLs), 15, and 18. Simulations show that QTL mapping resolution (the median distance between the QTL peak and true location) varied between 0.47 and 1.18 Mb. Most of the QTLs involved contrasts between wild-derived founder strains and therefore would not segregate between classical inbred strains. Use of variation data from the genomes of the CC founder strains refined these QTLs further and suggested several candidate genes. These results support the use of the CC for dissecting complex traits.
Related Links	http://dx.doi.org/10.1101/gr.118786.110
Ending Page	1248
Page Count	10
Starting Page	1239
File Format	PDF
ISSN	10889051
e-ISSN	15495469
Journal	Genome Research
Issue Number	8
Volume Number	21
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2011-08-01
Access Restriction	Open
Rights Holder	Cold Spring Harbor Laboratory Press
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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