Human Molecular Genetics, Vol 7, 1239-1243, Copyright © 1998 by Oxford University Press
TJ Watnick, MA Gandolph, H Weber, HP Neumann and GG Germino
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.
ARTICLES
Gene conversion is a likely cause of mutation in PKD1
Department of Medicine, The Johns Hopkins University School of Medicine, 970 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  O. Symmons, A. Varadi, and T. Aranyi How Segmental Duplications Shape Our Genome: Recent Evolution of ABCC6 and PKD1 Mendelian Disease Genes Mol. Biol. Evol., December 1, 2008; 25(12): 2601 - 2613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rossetti, M. B. Consugar, A. B. Chapman, V. E. Torres, L. M. Guay-Woodford, J. J. Grantham, W. M. Bennett, C. M. Meyers, D. L. Walker, K. Bae, et al. Comprehensive Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2143 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Harris, K. T. Bae, S. Rossetti, V. E. Torres, J. J. Grantham, A. B. Chapman, L. M. Guay-Woodford, B. F. King, L. H. Wetzel, D. A. Baumgarten, et al. Cyst Number but Not the Rate of Cystic Growth Is Associated with the Mutated Gene in Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3013 - 3019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Lyons, D. S. Biller, C. A. Erdman, M. J. Lipinski, A. E. Young, B. A. Roe, B. Qin, and R. A. Grahn Feline Polycystic Kidney Disease Mutation Identified in PKD1 J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2548 - 2555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Whelan and N. Goldman Estimating the Frequency of Events That Cause Multiple-Nucleotide Changes Genetics, August 1, 2004; 167(4): 2027 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Patel, L. Lu, R. T. Blaszak, and J. J. Bissler PKD1 intron 21: triplex DNA formation and effect on replication Nucleic Acids Res., February 27, 2004; 32(4): 1460 - 1468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Burtey, A M Lossi, J Bayle, Y Berland, and M Fontes Mutation screening of the PKD1 transcript by RT-PCR J. Med. Genet., June 1, 2002; 39(6): 422 - 429. [Full Text] [PDF]
|
|
|
|
|
|
M Luijten, R Fahsold, C Mischung, A Westerveld, P Nurnberg, and T J M Hulsebos Limited contribution of interchromosomal gene conversion to NF1 gene mutation J. Med. Genet., July 1, 2001; 38(7): 481 - 485. [Full Text]
|
|
|
|
|
|
J. A. Clikeman, S. L. Wheeler, and J. A. Nickoloff Efficient Incorporation of Large (>2 kb) Heterologies Into Heteroduplex DNA: Pms1/Msh2-Dependent and -Independent Large Loop Mismatch Repair in Saccharomyces cerevisiae Genetics, April 1, 2001; 157(4): 1481 - 1491. [Abstract] [Full Text]
|
|
|
|
|
|
J.-M. CHEN, O. RAGUENES, C. FEREC, P. H DEPREZ, and C. VERELLEN-DUMOULIN A CGC>CAT gene conversion-like event resulting in the R122H mutation in the cationic trypsinogen gene and its implication in the genotyping of pancreatitis J. Med. Genet., November 1, 2000; 37(11): 36e - 36. [Full Text]
|
|
|
|
|
|
J. A. Nickoloff, D. B. Sweetser, J. A. Clikeman, G. J. Khalsa, and S. L. Wheeler Multiple Heterologies Increase Mitotic Double-Strand Break-Induced Allelic Gene Conversion Tract Lengths in Yeast Genetics, October 1, 1999; 153(2): 665 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bacolla, A. Jaworski, T. D. Connors, and R. D. Wells PKD1 Unusual DNA Conformations Are Recognized by Nucleotide Excision Repair J. Biol. Chem., May 18, 2001; 276(21): 18597 - 18604. [Abstract] [Full Text] [PDF]
|
|