International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

Oral Presentation

Monday 18 November

20:30 - 20:45 HRS

THE GENETIC ARCHITECTURE OF EXPLORATORY AND FEAR-LIKE BEHAVIOR IN MICE: A COMPARISON OF THREE STRATEGIES FOR FINE MAPPING QTLs

H Gershenfeld
UT Southwestern

Co-Authors: 1) Lou Y, 1) Zhang S, 1) Amstein T, 2) Anyango M, 1) Mohibullah N, 2) Osoti A,2) King R, 2) Iraqi F
Institutions: 1) UT Southwestern, 2)International Livestock Research Institute

BACKGROUND: Prior work with (AxB) F2 and N2 crosses have defined loci on chr 1, 10, and 19 that influence open field (OF) and Light-Dark (LD) behaviors by quantitative trait loci (QTL) mapping in mice. METHODS: Interval Specific Congenic Strains (ISCS) for the telomeric chr 10 containing the Exq QTL were bred and studied. (AxB)F12 Advanced Intercross Line (AIL) mice (N=1130) and the (AxBxA) RI strain panel (N=26) were also phenotyped, genotyped, and mapped. RESULTS: The ISCS data suggest that the Exq locus is composed of two linked loci on distal chr. 10. The difficulties of a telomeric location are illustrated. The Exq locus mapped robustly with high statistical significance for LD behavior in the AIL. Surprisingly, the large regions containing OF loci on chr. 1 were localized to regions with weakly suggestive LOD scores, each explaining ~1% of the variance. RI strains were relatively unhelpful. CONCLUSIONS: These results suggest that gene interactions between linked loci may explain some of the non-replications and difficulties of genome mapping. Three findings may be generalizable to complex trait mapping, namely that 1) behavior results from inheriting "many small things" (i.e.,modest effect loci explaining 1-5% of the variance), 2) the congenic data suggest gene interactions exist where only combinations of loci have detectable effects, and 3) the genetic architecture underlying complex traits becomes the critical determinant of fine mapping success, highlighting the difference of loci acting in isolation in congenic strains versus the F12 AIL. Support: NIH Grant RO1 MH58882, Southwestern Medical Foundation, THECB