Genome-Wide Association Studies For Lactation Performance In Mice

Reproductive performance in mouse inbred strains is a highly variable trait as there are few strains which are highly fecund and easy to maintain while others are poor breeders and difficult to maintain. Although differences in lactation performance among a few inbred strains have been reported but this trait has not been comprehensively studied in a wide range of strains so as to perform genotype-phenotype correlation studies. Mouse models with varied lactation performance have a significant relevance in identifying novel genes associated with lactation performance in the high producing dairy cow. Lactation performance assessed indirectly by measuring pup weight gain among 11 different inbred strains of mice, identified QSi5 and FVB inbred strains as having greater lactation capacity whereas DBA/1, SJL and CBA/CaH were demonstrated to be low lactating strains. Whole genome association studies for this trait were performed with all markers from the first inbred mouse haplotype map both by single SNP and Haploview generated haplotype blocks.

A QTL for neonatal growth Neogq1 closely associated with lactation performance identified on chromosome 9 was fine mapped by adopting an integrated gene mapping strategy [1, 2]. Combining data from haplotype association analysis, regions of shared ancestry and gene expression profiling a quantitative trait gene (QTG) was found underlying the neonatal growth QTL. Comparative genomics approaches have helped us to map this QTL region to a meta-milk yield QTL on proximal chromosome 10 in cattle including this QTG. The Neogq1 gene was significantly over-represented in the high lactating QSi5 strain of mice relative to the CBA strain of mice.

Previously a unique nurturing ability QTL Naq1 was identified on mouse chromosome 5 and 12 genes were identified as primary candidate genes [3]. A single haplotype block of about 10.9 kb length with the highest chromosome-wide association for lactation performance was identified within the confidence interval of this QTL region on chromosome 5. This haplotype block overlapped with candidate genes that play a crucial role in reproduction.

References:

1.    Liljander, M., et al., Identification of genetic regions of importance for reproductive performance in female mice. Genetics., 2006. 173(2): p. 901-9. Epub 2006 Mar 17.
2.    Cervino, A.C., et al., An integrated in silico gene mapping strategy in inbred mice. Genetics., 2007. 175(1): p. 321-33. Epub 2006 Oct 8.
3.    Suto, J. and K. Sekikawa, Further mapping and characterization of Naq1, a quantitative trait locus responsible for maternal inferior nurturing ability in RR mice. J Vet Med Sci., 2004. 66(9): p. 1033-8.