A protocol for high-throughput phenotyping, suitable for quantitative trait analysis in mice.
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.
Solberg
Leah C
LC
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford Roosevelt Drive, Oxford, OX3 7BN, UK.
Valdar
William
W
Gauguier
Dominique
D
Nunez
Graciela
G
Taylor
Amy
A
Burnett
Stephanie
S
Arboledas-Hita
Carmen
C
Hernandez-Pliego
Polinka
P
Davidson
Stuart
S
Burns
Peter
P
Bhattacharya
Shoumo
S
Hough
Tertius
T
Higgs
Douglas
D
Klenerman
Paul
P
Cookson
William O
WO
Zhang
Youming
Y
Deacon
Robert M
RM
Rawlins
J Nicholas P
JN
Mott
Richard
R
Flint
Jonathan
J
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
D001786:Blood Glucose; D007328:Insulin