Pleiotropic patterns of quantitative trait loci for 70 murine skeletal traits

Abstract

Quantitative trait locus (QTL) studies of a skeletal trait or a few related skeletal components are becoming commonplace, but as yet there has been no investigation of pleiotropic patterns throughout the skeleton. We present a comprehensive survey of pleiotropic patterns affecting mouse skeletal morphology in an intercross of LG/J and SM/J inbred strains (N = 1040), using QTL analysis on 70 skeletal traits. We identify 798 single-trait QTL, coalescing to 105 loci that affect on average 7-8 traits each. The number of traits affected per locus ranges from only 1 trait to 30 traits. Individual traits average 11 QTL each, ranging from 4 to 20. Skeletal traits are affected by many, small-effect loci. Significant additive genotypic values average 0.23 standard deviation (SD) units. Fifty percent of loci show codominance with heterozygotes having intermediate phenotypic values. When dominance does occur, the LG/J allele tends to be dominant to the SM/J allele (30% vs. 8%). Over- and underdominance are relatively rare (12%). Approximately one-fifth of QTL are sex specific, including many for pelvic traits. Evaluating the pleiotropic relationships of skeletal traits is important in understanding the role of genetic variation in the growth and development of the skeleton.

Figure 1.—

Skeletal traits included in the study. (A–C) Cranial traits. (D) Mandible traits. (E) Innominate traits. (F) Vertebral traits, coded V#XN, where “#” is vertebral number, “X” is type (thoracic, lumbar, or caudal), and “N” is trait (1, 2, 3, C, or L, shown). (G) Foot traits. (H) Sacral traits. (I) Scapular traits. Not shown: body weights, tail length, long bone lengths. Figure after Anatomy of the Laboratory Mouse (Cook 1965).

Figure 2.—

Map of pleiotropic loci. Lengths of chromosomes are shown at the bottom. Bars indicate confidence intervals. The pleiotropic locus name is located at the position of maximum LPR for the locus.