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A gene for familial juvenile polyposis maps to chromosome 18q21.1
J R Howe1, J C Ringold, R W Summers
1Department of Surgery, University of Iowa College of Medicine, Iowa City, Iowa 52242-1086, USA. james-howe@uiowa.edu
Insights
Familial juvenile polyposis (FJP), a genetic disorder causing gastrointestinal polyps and cancer risk, has had its gene locus identified. Linkage analysis localized the FJP gene to chromosome 18q21.1, suggesting potential roles for DCC or DPC4.
Area of Science:
- Genetics
- Gastroenterology
- Oncology
Background:
- Familial juvenile polyposis (FJP) is an inherited condition characterized by hamartomatous polyps in the gastrointestinal tract.
- Individuals with FJP face an elevated risk of developing gastrointestinal cancers.
Purpose of the Study:
- To identify the genetic locus responsible for Familial Juvenile Polyposis (FJP) through a genome-wide screen.
- To investigate potential candidate genes within the identified chromosomal region.
Main Methods:
- Performed a focused genome screen using linkage analysis in a large family with FJP.
- Tested markers near known cancer-related genes and performed detailed analysis of recombinants.
Main Results:
- No linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS, CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1.
- Established linkage of FJP to chromosome 18q21.1, with a maximum LOD score of 5.00 at marker D18S1099.
- Narrowed the FJP gene location to an 11.9-cM interval between D18S1118 and D18S487, a region containing DCC and DPC4.
Conclusions:
- The primary gene responsible for FJP has been localized to chromosome 18q21.1.
- The tumor-suppressor genes DCC or DPC4 are potential candidates for causing FJP.
Abstract:
Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study was to perform a focused genome screen in a large family segregating FJP. No evidence for linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS, CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1. Linkage to FJP was established with several markers from chromosome 18q21.1. The maximum LOD score was 5.00, with marker D18S1099 (recombination fraction of .001). Analysis of critical recombinants places the FJP gene in an 11.9-cM interval bounded by D18S1118 and D18S487, a region that also contains the tumor-suppressor genes DCC and DPC4. These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by linkage, and they raise the possibility that either DCC or DPC4 could be responsible for FJP.