Nephrogenic Diabetes Insipidus: Close Linkage with Markers from the Distal Long Arm of the Human X Chromosome

Title: Nephrogenic Diabetes Insipidus: Close Linkage with Markers from the Distal Long Arm of the Human X Chromosome
Authors: van Oost, Bernard A.; Monnens, Leo A.H.; van der Heyden, H.; Ropers, Hilger H.; Knoers, Nine; Willems, J.
Publisher: Human Genetics
Date Published: September 01, 1988
Reference Number: 259
Ten families with nephrogenic diabetes insipidus (NDI) have been analysed for restriction fragment length polymorphisms (RFLPs). A search for linkage was performed using various chromosome-specific single-copy DNA probes of known regional assignment to the human X chromosome. Close linkage was found between the disease locus and the markers DXS52, DXS15, DXS134 and the F8 gene. This result assigns the NDI gene to the subtelomeric region of the long arm of the X chromosome. The regional localization of the gene by the identification of closely linked markers should have repercussions for genetic counselling and prevention in NDI families.

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)

The inheritance pattern for congenital nephrogenic diabetes insipidus (NDI) has been shown to be X-linked recessive. That means the gene that, when mutated, is responsible for NDI (which is referred to as the NDI gene) is located on the X chromosome. Finding out where on the X chromosome the NDI gene may be requires a different type of analysis called linkage analysis. This incorporates the use of genetic markers: any stretch of DNA, such as a gene, that has been identified and/or whose chromosomal location is known. Researchers use genetic markers to help them locate the chromosomal position of other genes; they know where the marker is located, and if the marker proves to be closely linked with the gene in question, then the gene's location can be assumed to be close to the markers to which they are listed.

Knoers, et al., took blood samples containing DNA material from a group of ten families with NDI patients. In all they had 19 NDI patients and 95 family members to draw from. They used seven DNA markers whose position on the X chromosome was known. Tight linkage was found between the NDI gene and four of the markers: DXS15, DXS52, F8 and DXS134. All these markers are located within band Xq28 on the X chromosome and are closely linked. Therefore, it is likely the NDI gene is also located in the Xq28 region of the X chromosome. Further, since all the families showed this linkage, it is likely that there is only a single gene responsible for NDI.

The authors found no evidence of a reciprocal exchange of genetic material between the NDI gene and each of the four markers. Thus, they could not determine where the NDI gene was positioned in relation to the markers. However, the observed lack of exchange between NDI and the four Xq28 markers suggests that the physical distance between them is very small. These closely linked markers should help diagnosticians determine if females in NDI families carry the NDI gene. This should also enable clinicians to perform accurate prenatal diagnosis of fetuses in NDI families. Such early detection can ensure timely and appropriate management of NDI, which can help prevent any complication of this disorder from arising.