Physical Delineation of a 700-kb Region Overlapping theLooptailMutation on Mouse Chromosome 1
Copyright policy )Physical Delineation of a 700-kb Region Overlapping theLooptailMutation on Mouse Chromosome 1
The mouse looptail (Lp) mutation is an established model for neural tube defects with homozygous Lp embryos showing an open neural tube from the caudal midbrain to the tip of the tail. Heterozygous Lp mice are characterized by a "looped-tail" and wobbly head movements. The Lp gene has been mapped to a 0.6-cM interval on mouse chromosome 1 delineated by two clusters of markers, Fcer1gamma/Usf1/D1Mit113/D1Wsu1 on the proximal side and Fcer1alpha/Spna1/D1Mit149 distally. In the present study, we have created a high-resolution physical map of the Lp genetic interval that is based on long-range restriction mapping by PFGE, fluorescence in situ hybridization analysis of interphase nuclei and extended chromatid fibers, and the assembly of a cloned contig. This contig consists of 25 independent and overlapping BAC clones and 3 YAC clones. The combined analysis indicates that the 0.6-cM genetic interval for Lp corresponds to a minimal physical interval of 700 kb that is delineated by D1Mit113 proximally (two crossovers) and Fcer1alpha distally (one crossover). The overall gene order and intergene distances for the region were determined to be D1Mit113-<150 kb-Nhlh1-250 kb-Atp1alpha2-280 kb-Fcer1alpha. Partial sequencing of BAC clones from the contig yielded 42 new STS markers for this region of mouse chromosome 1. Sequence analysis of the BAC clones and assignment of ESTs from the human transcript map to the cloned contig allowed the placement of four new transcription units within this region: Pc326, Kiaa0253, and Pea15 were positioned in the Nhlh1/Atp1alpha2 nonrecombinant interval, while Girk3 was located distal to Atp1alpha2.
- Ontario Institute for Cancer Research Canada
- University Health Network Canada
- McGill University Canada
- Princess Margaret Cancer Centre Canada
Molecular Sequence Data, Restriction Mapping, Chromosomes, Bacterial, Physical Chromosome Mapping, Contig Mapping, Mice, Mutation, Animals, Humans, Electrophoresis, Polyacrylamide Gel, Neural Tube Defects, Chromosomes, Artificial, Yeast, In Situ Hybridization, Fluorescence, Sequence Tagged Sites
Molecular Sequence Data, Restriction Mapping, Chromosomes, Bacterial, Physical Chromosome Mapping, Contig Mapping, Mice, Mutation, Animals, Humans, Electrophoresis, Polyacrylamide Gel, Neural Tube Defects, Chromosomes, Artificial, Yeast, In Situ Hybridization, Fluorescence, Sequence Tagged Sites
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