Genetic and genealogic study of 33 Finnish HNPCC kindreds
- Univ. of Helsinki (Finland); and others
Two susceptibility loci for hereditary nonpolyposis colorectal cancer (HNPCC) have been identified: MSH2 on chromosome 2p and MLH1 on chromosome 3p. This study focuses on the role of the latter locus in 33 Finnish HNPCC kindreds. Of 9 families in which linkage studies were possible, 8 revealed linkage to markers on 3p. A haplotype of alleles from 9 loci extending 10 cM around MLH1 was conserved in 5 kindreds. All families with the shared large haplotype as well as two other 3p-linked families with different disease haplotypes showed an identical germline mutation of MLH1. The mutation consists of a heterozygous deletion of 165 bp corresponding to an exon. An additional 24 kindreds that could not be studied for linkage were tested for the presence of the above described deletion, and the mutation was found in 6. The ancestries of all kindreds were traced 3 to 13 generations back using data from the church parish registers. Of the 13 families with the 165 bp deletion in MLH1, 10 originated in a limited area in south-central Finland. At least 8 of these kindreds had a common ancestry. The remaining kindreds with the MLH1 mutation originated from another small region some 200 km away. The kindreds that did not show the characteristic germline mutation originated more evenly in different parts of the country. Our results suggest that a single MLH1 mutation is a widespread cause of HNPCC in the Finnish population.
- OSTI ID:
- 133550
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0278
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Site-specific hereditary nonpolyposis colorectal cancer (HNPCC) which develops almost exclusively in males in a large SA kindred is linked to the hMLH1 gene on chromosome 3
The age of human mutation: Genealogical and linkage disequilibrium analysis of the CLN5 mutation in the Finnish population