Molecular mapping of the tubby (tub) mutation on mouse chromosome 7

Using 180 F2 progeny of a C57BL6/J >< CAST/Ei tub/+F1 intersubspecific intercross, a map of 28 molecular markers (including eight genes) on chromosome 7 surrounding the tub locus was generated. Using 33 obese F2 progeny, tub was localized approximately 50-52 cM distal to the centromere on mouse chromosome 7 in the interval defined proximally by hemoglobin beta (Hbb), D7Mit38, D7Mit2l7, D7Mit37, D7Mit96, and D7Mit33 and distally by D7Mit98. Using 39 obese F2 progeny from a similar intersubspecific intercross, a telomeric boundary of the interval defining tub was defined by D7Mit53; the order centromere-Hbb/tub-D7Mit53/ D7Mit328/D7Mit220-parathyroid hormone (Pth)-calcitonin (Calc)-zona pellucida 2 (2p2) was established. By combining the data from the two crosses, the most likely gene order on mouse chromosome 7 is centromere-Hbb-tub-Pth-Calc, thus making it likely that the human homolog of tub resides on 17p15, where the gene order HBB-PTH-CALC is conserved. Assignment of the human tubby homolog to 17p15 allows selection and development of polymorphic molecular markers that can be used to examine segregation of a human homolog of tubby in pedigrees segregating for obesity. The gene sulfonylurea receptor was eliminated as a candidate gene for tubby on the basis of its map position, approximately 3.1 +/- 3.1 cM centromeric of tyrosinase and approximately 14.9 +/- 4.8 cM centromeric of Hbb.