title: A protocol for high-throughput phenotyping, suitable for quantitative trait analysis in mice.
abstract: Whole-genome genetic association studies in outbred mouse populations represent a novel approach to identifying the molecular basis of naturally occurring genetic variants, the major source of quantitative variation between inbred strains of mice. Measuring multiple phenotypes in parallel on each mouse would make the approach cost effective, but protocols for phenotyping on a large enough scale have not been developed. In this article we describe the development and deployment of a protocol to collect measures on three models of human disease (anxiety, type II diabetes, and asthma) as well as measures of mouse blood biochemistry, immunology, and hematology. We report that the protocol delivers highly significant differences among the eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6 J, DBA/2 J, and LP/J), the progenitors of a genetically heterogeneous stock (HS) of mice. We report the successful collection of multiple phenotypes from 2000 outbred HS animals. The phenotypes measured in the protocol form the basis of a large-scale investigation into the genetic basis of complex traits in mice designed to examine interactions between genes and between genes and environment, as well as the main effects of genetic variants on phenotypes.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford Roosevelt Drive, Oxford, OX3 7BN, UK.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Solberg
authors.forename: William
authors.initials: W
authors.lastname: Valdar
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Graciela
authors.initials: G
authors.lastname: Nunez
authors.forename: Amy
authors.initials: A
authors.lastname: Taylor
authors.forename: Stephanie
authors.initials: S
authors.lastname: Burnett
authors.forename: Carmen
authors.initials: C
authors.lastname: Arboledas-Hita
authors.forename: Polinka
authors.initials: P
authors.lastname: Hernandez-Pliego
authors.forename: Stuart
authors.initials: S
authors.lastname: Davidson
authors.forename: Peter
authors.initials: P
authors.lastname: Burns
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Tertius
authors.initials: T
authors.lastname: Hough
authors.forename: Douglas
authors.initials: D
authors.lastname: Higgs
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: William O
authors.initials: WO
authors.lastname: Cookson
authors.forename: Youming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Deacon
authors.forename: J Nicholas P
authors.initials: JN
authors.lastname: Rawlins
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000818:Animals; D001007:Anxiety / Q000097:blood / Q000235:genetics / Q000523:psychology; D001249:Asthma / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D001522:Behavior, Animal; D001786:Blood Glucose / Q000032:analysis; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D016678:Genome; D005951:Glucose Tolerance Test; D016130:Immunophenotyping; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D010991:Plethysmography; D019655:Quantitative Trait, Heritable; D013045:Species Specificity; D014945:Wound Healing
chemical_list: D001786:Blood Glucose; D007328:Insulin