IDENTIFICATION AND CHARACTERIZATION OF A NOVEL CONSERVED DNA REPEAT

Homozygous In(10)17Rk mice contain a paracentric inversion within Chro mosome (Chr) 10 and exhibit a pygmy phenotype, suggesting that the dis tal inversion breakpoint is within the pygmy (pg) locus. In order to o btain the pygmy gene by positional cloning procedures, In(10)17Rk DNA was subjected to RFLP analysis with single-copy probes derived from th e wild-type pygmy locus. This analysis identified a DNA polymorphism i n the DBA/2J mouse strain on which the In(10)17Rk mutation was origina lly induced. A detailed characterization of this polymorphism revealed the presence of a novel, tandemly repeated DNA element. Copy number e stimation experiments indicate that there are approximately 100,000 co pies of this element in the haploid DBA/2J genome. PCR typing studies revealed the presence of the repeat at the pygmy locus of 6 of the 18 Mus domesticus strains analyzed. The absence of the repeat from the py gmy locus of 12 strains of the M. domesticus species and from the M. c aroli, M. spretus, M. castaneus, and M. molossinus species suggests th at the repeat could serve as a strain-specific hybridization probe in genetic mapping studies. Finally, the novel tandem DNA repeat is conse rved in both rat and human genomes as indicated by Southern hybridizat ion experiments.