Analysis of Aneuploidy Frequencies in Sperm from Patients with Hereditary Nonpolyposis Colon Cancer and an hMSH2 Mutation
| Autor: | Alfred Rademaker, Leona Barclay, Renée H. Martin, Jane Green, Evelyn Ko |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Heterozygote congenital hereditary and neonatal diseases and abnormalities DNA Repair DNA repair Base Pair Mismatch Newfoundland and Labrador Cancer Hereditary nonpolyposis colon (HNPCC) Aneuploidy Biology Meiosis Gene Frequency Report Chromosome Segregation Proto-Oncogene Proteins medicine Genetics Humans Genetics(clinical) Allele frequency Genetics (clinical) In Situ Hybridization Fluorescence Sex Chromosomes hMSH2 mutation Fluorescence in situ hybridization Chromosome nutritional and metabolic diseases Exons Middle Aged medicine.disease Sperm Colorectal Neoplasms Hereditary Nonpolyposis Diploidy Spermatozoa digestive system diseases DNA-Binding Proteins MutS Homolog 2 Protein Mutation (genetic algorithm) Mutation Chromosome(s) Abnormalities DNA mismatch repair |
| Zdroj: | The American Journal of Human Genetics. 66(3):1149-1152 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/302805 |
| Popis: | Hereditary nonpolyposis colon cancer (HNPCC) has been shown to be caused by mutations in the mismatch repair genes hMSH2, hMLH1, hPMS1, and hPMS2. Recent evidence has demonstrated that mutations in mismatch repair genes disrupt meiosis in mice. A large HNPCC kindred in Newfoundland, Canada, has an hMSH2 mutation-an A--T transversion at the +3 position of the splice-donor site of exon 5. We have studied sperm from men with this hMSH2 mutation, since it is possible that mismatch repair mutations in humans might also have an effect on meiosis and normal segregation of chromosomes. The frequencies of aneuploid and diploid sperm were determined in 10 men with the hMSH2 mutation, by use of multicolor FISH analysis for chromosomes 13, 21, X, and Y. A minimum of 10,000 sperm per man was studied per chromosome probe. Control individuals consisted of men in the same kindred with HNPCC who did not carry the mutation and of other normal men from Newfoundland. A total of 321,663 sperm were analyzed: 200,905 sperm were from men carrying the hMSH2 mutation and 120,758 sperm were from control men. There was a significantly increased frequency of disomy 13, disomy 21, XX, and diploidy in mutation carriers compared with control men. These results suggest that the hMSH2 mutation may affect meiosis in humans. |
| Databáze: | OpenAIRE |
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