Gene conversion is a likely cause of mutation in PKD1

Terry J. Watnick, Michael A. Gandolph, Horst Weber, Hartmut P H Neumann, Gregory G. Germino

Research output: Contribution to journalArticle

Abstract

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease (PKD1) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1, and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.

Original languageEnglish (US)
Pages (from-to)1239-1243
Number of pages5
JournalHuman Molecular Genetics
Volume7
Issue number8
StatePublished - Aug 1998

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Gene Conversion
Mutation
Genes
Autosomal Dominant Polycystic Kidney
Chromosomes, Human, Pair 16
Pseudogenes
Hybrid Cells
Base Pairing
Exons
Rodentia
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

Watnick, T. J., Gandolph, M. A., Weber, H., Neumann, H. P. H., & Germino, G. G. (1998). Gene conversion is a likely cause of mutation in PKD1. Human Molecular Genetics, 7(8), 1239-1243.

Gene conversion is a likely cause of mutation in PKD1. / Watnick, Terry J.; Gandolph, Michael A.; Weber, Horst; Neumann, Hartmut P H; Germino, Gregory G.

In: Human Molecular Genetics, Vol. 7, No. 8, 08.1998, p. 1239-1243.

Research output: Contribution to journalArticle

Watnick, TJ, Gandolph, MA, Weber, H, Neumann, HPH & Germino, GG 1998, 'Gene conversion is a likely cause of mutation in PKD1', Human Molecular Genetics, vol. 7, no. 8, pp. 1239-1243.
Watnick TJ, Gandolph MA, Weber H, Neumann HPH, Germino GG. Gene conversion is a likely cause of mutation in PKD1. Human Molecular Genetics. 1998 Aug;7(8):1239-1243.
Watnick, Terry J. ; Gandolph, Michael A. ; Weber, Horst ; Neumann, Hartmut P H ; Germino, Gregory G. / Gene conversion is a likely cause of mutation in PKD1. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 8. pp. 1239-1243.
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