Genetic Linkage Map of Six Polymorphic DNA Markers Around the Gene for Familial Adenomatous Polyposis on Chromosome 5

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1990 Dec 1

PMID 1978564

Citations 13

Authors

M G Dunlop

A H Wyllie

Y Nakamura

C M Steel

H J Evans

R L White

C C Bird

Affiliations

Soon will be listed here.

Abstract

A genetic linkage map of six polymorphic DNA markers close to the gene (APC) for familial adenomatous polyposis (FAP) on chromosome 5q is reported. One hundred fifty-five typed members of nine FAP kindred provided more than 90 meioses for linkage analysis. A number of crucial recombination events have been identified which are informative at three or more loci, allowing confident ordering of parts of the map. There was no evidence of genetic heterogeneity, with all families showing linkage of at least one chromosome 5 marker to the gene. Recombination data and two-point linkage analysis support a locus order of centromere-pi 227-C11P11-ECB27-L5.62-APC-EF5.44-YN5.48-telomer e, although EF5.44 could lie in the interval L5.62-APC or ECB27-L5.62. No recombinants were identified between APC and either EF5.44 or YN5.48, but published deletion mapping in colorectal carcinomas and linkage analysis in FAP suggest that YN5.48 is 1-3 cM from APC. The present study suggests that YN5.48 and L5.62 delineate a small region of chromosome 5 within which the EF5.44 locus lies very close to the APC gene. These data not only allow use of flanking markers for presymptomatic diagnosis of FAP but also provide a high-density map of the region for isolation of the APC gene itself and for further assessment of the role of chromosome 5 deletions in the biology of sporadic colorectal cancer.

Citing Articles

Germ-line mutations in the first 14 exons of the adenomatous polyposis coli (APC) gene.

Olschwang S, Laurent-Puig P, Groden J, White R, Thomas G Am J Hum Genet. 1993; 52(2):273-9.

PMID: 8381580 PMC: 1682179.

Allele loss from 5q21 (APC/MCC) and 18q21 (DCC) and DCC mRNA expression in breast cancer.

Thompson A, Morris R, Wallace M, Wyllie A, Steel C, Carter D Br J Cancer. 1993; 68(1):64-8.

PMID: 8318422 PMC: 1968317. DOI: 10.1038/bjc.1993.287.

Linkage studies in Italian families with familial adenomatous polyposis.

Mareni C, Stella A, Origone P, Susca F, Montera M, Lonoce A Hum Genet. 1993; 90(5):545-50.

PMID: 8094067 DOI: 10.1007/BF00217456.

Congenital hypertrophy of the retinal pigment epithelium and mandibular osteomata as markers in familial colorectal cancer.

Hunt L, Robinson M, Hugkulstone C, Clarke B, Vernon S, Gregson R Br J Cancer. 1994; 70(1):173-6.

PMID: 8018532 PMC: 2033331. DOI: 10.1038/bjc.1994.271.

APC mutation analysis by chemical cleavage of mismatch and a protein truncation assay in familial adenomatous polyposis.

Prosser J, Condie A, Wright M, Horn J, Fantes J, Wyllie A Br J Cancer. 1994; 70(5):841-6.

PMID: 7524601 PMC: 2033526. DOI: 10.1038/bjc.1994.408.

References

Knudson Jr A . Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971; 68(4):820-3. PMC: 389051. DOI: 10.1073/pnas.68.4.820. View

Ashton-Rickardt P, Dunlop M, Nakamura Y, Morris R, Purdie C, Steel C . High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21-22. Oncogene. 1989; 4(10):1169-74. View

Nakamura Y, Lathrop M, Leppert M, Dobbs M, Wasmuth J, Wolff E . Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet. 1988; 43(5):638-44. PMC: 1715544. View

Cooke H, Brown W, Rappold G . Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature. 1985; 317(6039):687-92. DOI: 10.1038/317687a0. View

Bodmer W, Bailey C, Bodmer J, Bussey H, Ellis A, Gorman P . Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987; 328(6131):614-6. DOI: 10.1038/328614a0. View

Leppert M, Burt R, Hughes J, Samowitz W, Nakamura Y, Woodward S . Genetic analysis of an inherited predisposition to colon cancer in a family with a variable number of adenomatous polyps. N Engl J Med. 1990; 322(13):904-8. DOI: 10.1056/NEJM199003293221306. View

Bulow S . Familial polyposis coli. Dan Med Bull. 1987; 34(1):1-15. View

Meera Khan P, Tops C, vd Broek M, Breukel C, Wijnen J, Oldenburg M . Close linkage of a highly polymorphic marker (D5S37) to familial adenomatous polyposis (FAP) and confirmation of FAP localization on chromosome 5q21-q22. Hum Genet. 1988; 79(2):183-5. DOI: 10.1007/BF00280563. View

Varesco L, Thomas H, Cottrell S, Murday V, Fennell S, Williams S . CpG island clones from a deletion encompassing the gene for adenomatous polyposis coli. Proc Natl Acad Sci U S A. 1989; 86(24):10118-22. PMC: 522387. DOI: 10.1073/pnas.86.24.10118. View

10.

Cannon-Albright L, Skolnick M, Bishop D, Lee R, Burt R . Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988; 319(9):533-7. DOI: 10.1056/NEJM198809013190902. View

11.

Sondergaard J, Svendsen L, Witt I, Bulow S, Lauritsen K, Tetens G . Mandibular osteomas in the cancer family syndrome. Br J Cancer. 1985; 52(6):941-3. PMC: 1977264. DOI: 10.1038/bjc.1985.281. View

12.

Tops C, Wijnen J, Griffioen G, von Leeuwen I, Vasen H, den Hartog Jager F . Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers. Lancet. 1989; 2(8676):1361-3. DOI: 10.1016/s0140-6736(89)91968-5. View

13.

MACKLIN M . Inheritance of cancer of the stomach and large intestine in man. J Natl Cancer Inst. 1960; 24:551-71. DOI: 10.1093/jnci/24.3.551. View

14.

Leppert M, Dobbs M, Scambler P, OConnell P, Nakamura Y, Stauffer D . The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987; 238(4832):1411-3. DOI: 10.1126/science.3479843. View

15.

Reed T, Neel J . A genetic study of multiple polyposis of the colon with an appendix deriving a method of estimating relative fitness. Am J Hum Genet. 1955; 7(3):236-63. PMC: 1716610. View

16.

Lovett E . Family studies in cancer of the colon and rectum. Br J Surg. 1976; 63(1):13-18. DOI: 10.1002/bjs.1800630103. View

17.

Woolf C . A genetic study of carcinoma of the large intestine. Am J Hum Genet. 1958; 10(1):42-7. PMC: 1931863. View

18.

Dunlop M, Steel C, Wyllie A, Bird C, Evans H . Linkage analysis in familial adenomatous polyposis: order of C11P11 (D5S71) and pi 227 (D5S37) loci at the apc gene. Genomics. 1989; 5(2):350-3. DOI: 10.1016/0888-7543(89)90068-2. View

19.

Duncan J, Kyle J . Family incidence of carcinoma of the colon and rectum in north-east Scotland. Gut. 1982; 23(2):169-71. PMC: 1419542. DOI: 10.1136/gut.23.2.169. View

20.

Lynch H, Kimberling W, Albano W, Lynch J, Biscone K, Schuelke G . Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource. Cancer. 1985; 56(4):934-8. DOI: 10.1002/1097-0142(19850815)56:4<934::aid-cncr2820560439>3.0.co;2-i. View