Colocalization of the Gene for Nephrogenic Diabetes Insipidus (DIR) and the Vasopressin Type 2 Receptor Gene (AVPR2) in the Xq28 Region

Title: Colocalization of the Gene for Nephrogenic Diabetes Insipidus (DIR) and the Vasopressin Type 2 Receptor Gene (AVPR2) in the Xq28 Region
Authors: Ouweland, Ans M.W. van den; Knoop, M.T.; Knoers, Nine; Markslag, P.W.B.; Rocchi, Mariano; Warren, Ph.D., Stephen T.; Ropers, Hilger H.; Fahrenholz, Falk; Monnens, Leo A.H.; van Oost, Bernard A.
Publisher: Genomics
Date Published: August 01, 1992
Reference Number: 302
The gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) have both been localized in the Xqter region by genetic mapping and functional expression studies, respectively. In this paper genetic evidence that the DIR locus is localized distal to the DXS305 locus and that the functional gene for the V2 receptor is localized between the markers DXS269 and F8 is presented. These further refinements in the localization of both genes strengthen the assumption that both genes are identical and provide a rationale for cloning the gene by reversed genetics strategies.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Researchers will often employ a genetic marker or a group of genetic markers to try to determine the chromosomal location of a particular gene. A genetic marker is a segment of DNA, such as a gene, that can be identified, or whose chromosomal location is known. Since its location is known, it can be used to map or locate other genes. Any gene which has a known phenotype (i.e. the researchers know the trait the gene expresses) that can be used to track the presence of or absence of other genes on the same piece of DNA may be called a genetic marker.

Researchers analyze a series of genetic crossings (exchanges of genetic material) to see if whenever the expression of their marker occurs, the expression of the gene they are looking for occurs. If they find the two occur together at a high enough percentage, then the researchers can infer the gene and the markers are linked and are located close to each other.

Researchers have long suspected that the gene that, when mutated, causes nephrogenic diabetes insipidus (NDI) is the vasopressin-2 receptor (AVPR2) gene. Previous linkage analysis had located the NDI gene to the Xqter region of the X chromosome. The AVPR2 gene also has been located in the Xqter region. This strengthens the suspicion that the NDI gene and the AVPR2 gene are one and the same. In this paper, van den Ouweland, et al., report on their work which further refines and clarifies the location of both the NDI gene and the AVPR2 gene.

Using the genetic markers DXS305 and DX552, the researchers found that the location of the NDI gene was 10,000 times more likely to be beyond marker DXS305 than near to it. The authors then mapped the AVPR2 gene more precisely. Previous studies where researchers injected X chromosome fragments into cell cultures, and then measured for AVPR2 activity, indicated that X chromosome fragments that carried at least the Xq27-qter region showed signs of AVPR2 activity. van den Ouweland, et al, using the same methodology, showed that the X segment shared by all the cell cultures that showed AVPR2 activity (which indicates the presence of the AVPR2 gene) fall between the FMR1 and FVIII genes on the X chromosome.

Combining these findings with the previous linkage analysis enabled the authors to determine that both the NDI gene and the AVPR2 gene are located in the X128 region of the X chromosome within a very small region flanked by markers DXS305 and FVIII. This refinement of localization of both genes strengthens the suspicion that the NDI gene and the AVPR2 gene are one and the same.