Fine-mapping of a quantitative trait locus (QTL) affecting skeletal size in mice

CHRISTIANS, JK *; BINGHAM, V; KEIGHTLEY, PD; University of Edinburgh, United Kingdom: Fine-mapping of a quantitative trait locus (QTL) affecting skeletal size in mice

Many traits of medical, agricultural or evolutionary significance show continuous variation (e.g., body size), rather than having discrete, one-or-the-other states (e.g., blood types). In recent years, numerous studies have used molecular markers to identify chromosomal regions that influence continuous variation in a variety of traits (i.e., quantitative trait loci, or QTL). While mapping the position of QTL with sufficient precision to identify the underlying genes has proven extremely difficult, our experimental system promises the potential to achieve the necessary resolution thanks to a relatively large effect size and a trait that is easily measured. We are investigating a QTL affecting adult tail length originally identified in an F2 population of C57BL/6J x DBA/2J mice. By testing a large population of progeny from parents that are recombinant within the region of the QTL (ca. 1000 offspring from 61 parents recombinant within a 13 centimorgan interval), we have refined its position to a region of approximately 2 centimorgans (~ 4 megabases) containing an estimated 30 genes. Preliminary results indicate that this QTL has a general effect on skeletal size, affecting the length of the humerus, femur, tibia, mandible, scapula, pelvic girdle and a tail bone. However, no significant effect was found on the number of bones in the tail or on the dimensions of the ulna, skull, or first vertebra. Pleiotropic effects of the QTL on fecundity, as well as the interaction between genotype and environment (i.e., litter size) will also be discussed.

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