The International Complex Trait Consortium

A New Panel of Recombinant Inbred Strains from ILS and ISS

Beth Bennett1, Thomas E. Johnson1, Robert W. Williams2

1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309-0447
2University of Tennessee Health Science Center, Center of Genomics and Bioinformatics, Memphis, TN 38163 USA

This is the first report of the use of a new incipient recombinant inbred (RI) series (LXS; “Lexus”) derived from Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) parental strains. This RI series, with over 90% of the strains fully inbred, has 79 strains still extant, and is the largest mouse RI panel in existence. RI strains of mice are useful for determining genetic correlations, heritability estimates, and for genetic mapping. A large panel of RI strains provides impressive power for genetic mapping because within strain genotypes are identical, allowing for replication in phenotypic assays. For example, in an RI panel of 25 strains, when independent confirmation of the QTL is planned, a QTL accounting for 26% of the genetic variance can be detected reliably (power > 0.8). With 100 strains, a QTL accounting for 7% of the genetic variance can be detected. Once the strain genotypes are completed, with dense marker coverage, mapping of desired traits involves testing each strain and then combining phenotypic data with genotype data (which will be available on our web site) in a mapping algorithm such as MapManagerQTL. Females in generations 13 and 20 were weighed at 30-day intervals between 30 and 150 days. Putative QTLs for this body weight at these ages have been identified. One QTL on chromosome 5 emerged at 90, 120, and 150 days with a maximum LRS of 14.6. We have also begun to use this panel to map genetically a variety of alcohol-related traits including acute functional tolerance, very rapid acute functional tolerance, hypothermia following high dose ethanol, and low dose activation. We also plan to make these mice available to the mouse research community. We screened 813 microsatellite markers over all 20 mouse chromosomes; 361 were polymorphic, giving an average coverage of 1 marker every 4.4 cM. To date, they have been genotyped for 233 microsatellite markers producing a strain distribution pattern with an average map coverage of one marker every 6.9 cM. Genotyping began upon completion of marker screening at approximately generation 18 of inbreeding, when about 96% of the loci should be fixed. All parents (from harem matings) of any given incipient strain were genotyped, allowing us to determine if the marker locus was fixed. Markers at approximately 4.8 cM coverage of the genome have now been typed.

[This work was supported by NIH: RO1 AA11984 and P20 MH62009]