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Identification of a deletion in the mismatch repair gene, MSH2, using mouse-human cell hybrids monosomal for chromosome 2.

Authors :
Pyatt RE
Nakagawa H
Hampel H
Sedra M
Fuchik MB
Comeras I
de la Chapelle A
Prior TW
Source :
Clinical genetics [Clin Genet] 2003 Mar; Vol. 63 (3), pp. 215-8.
Publication Year :
2003

Abstract

Hereditary non-polyposis colorectal cancer is characterized by mutations in one of the DNA mismatch repair genes, primarily MLH1, MSH2, or MSH6. We report here the identification of a genomic deletion of approximately 11.4 kb encompassing the first two exons of the MSH2 gene in two generations of an Ohio family. By Southern blot analysis, using a cDNA probe spanning the first seven exons of MSH2, an alteration in each of three different enzyme digests (including a unique 13-kb band on HindIII digests) was observed, which suggested the presence of a large alteration in the 5' region of this gene. Mouse-human cell hybrids from a mutation carrier were then generated which contained a single copy each of human chromosome 2 on which the MSH2 gene resides. Southern blots on DNA from the cell hybrids demonstrated the same, unique 13-kb band from one MSH2 allele, as seen in the diploid DNA. DNA from this same monosomal cell hybrid failed to amplify in polymerase chain reactions (PCRs) using primers to exons 1 and 2, demonstrating the deletion of these sequences in one MSH2 allele, and the breakpoints involving Alu repeats were identified by PCR amplification and sequence analysis.<br /> (Copyright Blackwell Munksgaard, 2003)

Details

Language :
English
ISSN :
0009-9163
Volume :
63
Issue :
3
Database :
MEDLINE
Journal :
Clinical genetics
Publication Type :
Academic Journal
Accession number :
12694232
Full Text :
https://doi.org/10.1034/j.1399-0004.2003.00040.x