Mapping major quantitative trait loci for postnatal growth in an intersubspecific backcross between C57BL/6J and Philippine wild mice by using principal component analysis.

Abstract

A number of quantitative trait loci (QTLs) for postnatal growth have previously been reported in mice. As effects of the QTLs are usually small and similar to one another in magnitude, it is generally difficult to know which loci are major contributors to postnatal growth. We applied principal component analysis to a genome-wide search for QTLs affecting postnatal growth in body weight weekly recorded from 3 to 10 weeks of age in an intersubspecific backcross population of C57BL/6J inbred mice (Mus musculus domesticus) and wild mice (M. m. castaneus) captured in the Philippines, in order to discover new QTLs from a gene pool of the wild mice and uncover major loci underlying variation in postnatal growth. Principal component analysis classified phenotypic variation in body weights at different ages into two independent principal components: the first principal component (PC1) extracted information on the entire growth process and the second principal component (PC2) contrasted middle (3-6 weeks of age) with late (6-10 weeks) growth phases. Simple interval mapping and composite interval mapping revealed 10 significant QTLs with main effects on PC1 or PC2 on eight chromosomes. Of these, the six main-effect QTLs interacted epistatically with one another or three new additional QTLs on different chromosomal regions without main effects. Several of the identified QTLs with main effects and/or epistatic interaction effects appeared to be sex specific. These results suggest that the identified 13 QTLs, most of which affected the entire growth process, are very important contributors to complex genetic networks of postnatal growth.