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Comparative mapping on the mouse and human X chromosomes of a human cDNA clone encoding the vasopressin renal-type
C J Faust1, J C Gonzales, A Seibold
1Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
Abstract:
Mutations in the gene for the human renal-type vasopressin receptor (V2R) have recently been identified in patients with nephrogenic diabetes insipidus (NDI). Both V2R and NDI have been independently mapped to Xq28. Using a combination of genetic and physical mapping, we have localized the murine V2r locus to within 100 kb of L1Cam on the mouse X chromosome in a region syntenic with human Xq28. Based on conserved gene order of mouse and human loci in this region, physical mapping using DNA derived from human lymphoblasts has established that the corresponding human loci V2R and L1CAM are linked within 210 kb. The efficiency and precision of genetic mapping of V2r and other loci in the mouse suggest that it might be easier to map additional human genes in the mouse first and infer the corresponding human location. More precise physical mapping in man could then be performed using pulsed-field gel electrophoresis and/or yeast artificial chromosomes.
Insights
Genetic mapping identified the mouse V2r gene near L1Cam on the X chromosome. This finding aids in understanding human nephrogenic diabetes insipidus (NDI) by providing a model for gene localization and physical mapping.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Mutations in the human vasopressin V2 receptor (V2R) gene are linked to nephrogenic diabetes insipidus (NDI).
- Both the V2R gene and NDI have been mapped to chromosome Xq28.
Purpose of the Study:
- To map the murine V2r locus on the mouse X chromosome.
- To establish the physical and genetic linkage between V2r and L1Cam in mice.
- To leverage mouse models for improved human gene mapping.
Main Methods:
- Combined genetic and physical mapping techniques in mice.
- Analysis of DNA from human lymphoblasts for physical mapping.
- Utilized conserved syntenic regions between mouse and human X chromosomes.
Main Results:
- The murine V2r locus was localized within 100 kb of the L1Cam gene on the mouse X chromosome.
- The mouse chromosomal region is syntenic with human Xq28.
- Human V2R and L1CAM loci were found to be linked within 210 kb.
Conclusions:
- The mouse X chromosome provides an efficient system for mapping genes homologous to human X-linked disorders.
- The proximity of V2r and L1Cam in mice facilitates comparative mapping with humans.
- This approach can guide more precise physical mapping of human genes using techniques like pulsed-field gel electrophoresis and yeast artificial chromosomes.