Genome-Wide Association Studies For Lactation Performance In Mice
Palaniappan Ramanathan, Peter Thomson, Ian Martin, Christopher Moran and Peter Williamson - University of Sydney
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 . 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.
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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.