2.50
Hdl Handle:
http://hdl.handle.net/10033/237071
Title:
The genome architecture of the Collaborative Cross mouse genetic reference population.
Abstract:
The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multiparental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.
Citation:
The genome architecture of the Collaborative Cross mouse genetic reference population. 2012, 190 (2):389-401 Genetics
Journal:
Genetics
Issue Date:
Feb-2012
URI:
http://hdl.handle.net/10033/237071
DOI:
10.1534/genetics.111.132639
PubMed ID:
22345608
Type:
Article
Language:
en
ISSN:
1943-2631
Appears in Collections:
Publications of JRG Infection Genetics (INFG)

Full metadata record

DC FieldValue Language
dc.date.accessioned2012-08-02T13:57:39Z-
dc.date.available2012-08-02T13:57:39Z-
dc.date.issued2012-02-
dc.identifier.citationThe genome architecture of the Collaborative Cross mouse genetic reference population. 2012, 190 (2):389-401 Geneticsen_GB
dc.identifier.issn1943-2631-
dc.identifier.pmid22345608-
dc.identifier.doi10.1534/genetics.111.132639-
dc.identifier.urihttp://hdl.handle.net/10033/237071-
dc.description.abstractThe Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multiparental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Geneticsen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBreedingen_GB
dc.subject.meshCrosses, Geneticen_GB
dc.subject.meshExtinction, Biologicalen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFounder Effecten_GB
dc.subject.meshGenomeen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshLinkage Disequilibriumen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred Strainsen_GB
dc.subject.meshReproductionen_GB
dc.titleThe genome architecture of the Collaborative Cross mouse genetic reference population.en
dc.typeArticleen
dc.identifier.journalGeneticsen_GB

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