Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1990 Dec;47(6):982–987.

Genetic linkage map of six polymorphic DNA markers around the gene for familial adenomatous polyposis on chromosome 5.

M G Dunlop 1, A H Wyllie 1, Y Nakamura 1, C M Steel 1, H J Evans 1, R L White 1, C C Bird 1
PMCID: PMC1683900  PMID: 1978564

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.

Full text

PDF
982

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashton-Rickardt P. G., Dunlop M. G., Nakamura Y., Morris R. G., Purdie C. A., Steel C. M., Evans H. J., Bird C. C., Wyllie A. H. High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21-22. Oncogene. 1989 Oct;4(10):1169–1174. [PubMed] [Google Scholar]
  2. Bodmer W. F., Bailey C. J., Bodmer J., Bussey H. J., Ellis A., Gorman P., Lucibello F. C., Murday V. A., Rider S. H., Scambler P. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987 Aug 13;328(6131):614–616. doi: 10.1038/328614a0. [DOI] [PubMed] [Google Scholar]
  3. Bonelli L., Martines H., Conio M., Bruzzi P., Aste H. Family history of colorectal cancer as a risk factor for benign and malignant tumours of the large bowel. A case-control study. Int J Cancer. 1988 Apr 15;41(4):513–517. doi: 10.1002/ijc.2910410407. [DOI] [PubMed] [Google Scholar]
  4. Bülow S. Familial polyposis coli. Dan Med Bull. 1987 Mar;34(1):1–15. [PubMed] [Google Scholar]
  5. Cannon-Albright L. A., Skolnick M. H., Bishop D. T., Lee R. G., Burt R. W. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988 Sep 1;319(9):533–537. doi: 10.1056/NEJM198809013190902. [DOI] [PubMed] [Google Scholar]
  6. Cooke H. J., Brown W. R., Rappold G. A. Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature. 1985 Oct 24;317(6039):687–692. doi: 10.1038/317687a0. [DOI] [PubMed] [Google Scholar]
  7. Duncan J. L., Kyle J. Family incidence of carcinoma of the colon and rectum in north-east Scotland. Gut. 1982 Feb;23(2):169–171. doi: 10.1136/gut.23.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dunlop M. G., Steel C. M., Wyllie A. H., Bird C. C., Evans H. J. Linkage analysis in familial adenomatous polyposis: order of C11P11 (D5S71) and pi 227 (D5S37) loci at the apc gene. Genomics. 1989 Aug;5(2):350–353. doi: 10.1016/0888-7543(89)90068-2. [DOI] [PubMed] [Google Scholar]
  9. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leppert M., Burt R., Hughes J. P., Samowitz W., Nakamura Y., Woodward S., Gardner E., Lalouel J. M., White R. Genetic analysis of an inherited predisposition to colon cancer in a family with a variable number of adenomatous polyps. N Engl J Med. 1990 Mar 29;322(13):904–908. doi: 10.1056/NEJM199003293221306. [DOI] [PubMed] [Google Scholar]
  11. Leppert M., Dobbs M., Scambler P., O'Connell P., Nakamura Y., Stauffer D., Woodward S., Burt R., Hughes J., Gardner E. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987 Dec 4;238(4832):1411–1413. doi: 10.1126/science.3479843. [DOI] [PubMed] [Google Scholar]
  12. Lovett E. Family studies in cancer of the colon and rectum. Br J Surg. 1976 Jan;63(1):13–18. doi: 10.1002/bjs.1800630103. [DOI] [PubMed] [Google Scholar]
  13. Lynch H. T., Kimberling W., Albano W. A., Lynch J. F., Biscone K., Schuelke G. S., Sandberg A. A., Lipkin M., Deschner E. E., Mikol Y. B. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource. Cancer. 1985 Aug 15;56(4):934–938. doi: 10.1002/1097-0142(19850815)56:4<934::aid-cncr2820560439>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  14. MACKLIN M. T. Inheritance of cancer of the stomach and large intestine in man. J Natl Cancer Inst. 1960 Mar;24:551–571. doi: 10.1093/jnci/24.3.551. [DOI] [PubMed] [Google Scholar]
  15. Meera Khan P., Tops C. M., vd Broek M., Breukel C., Wijnen J. T., Oldenburg M., vd Bos J., van Leeuwen-Cornelisse I. S., Vasen H. F., Griffioen G. 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 Jun;79(2):183–185. doi: 10.1007/BF00280563. [DOI] [PubMed] [Google Scholar]
  16. Nakamura Y., Lathrop M., Leppert M., Dobbs M., Wasmuth J., Wolff E., Carlson M., Fujimoto E., Krapcho K., Sears T. Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet. 1988 Nov;43(5):638–644. [PMC free article] [PubMed] [Google Scholar]
  17. REED T. E., NEEL J. V. A genetic study of multiple polyposis of the colon with an appendix deriving a method of estimating relative fitness. Am J Hum Genet. 1955 Sep;7(3):236–263. [PMC free article] [PubMed] [Google Scholar]
  18. Sasaki M., Okamoto M., Sato C., Sugio K., Soejima J., Iwama T., Ikeuchi T., Tonomura A., Miyaki M., Sasazuki T. Loss of constitutional heterozygosity in colorectal tumors from patients with familial polyposis coli and those with nonpolyposis colorectal carcinoma. Cancer Res. 1989 Aug 15;49(16):4402–4406. [PubMed] [Google Scholar]
  19. Solomon E., Voss R., Hall V., Bodmer W. F., Jass J. R., Jeffreys A. J., Lucibello F. C., Patel I., Rider S. H. Chromosome 5 allele loss in human colorectal carcinomas. Nature. 1987 Aug 13;328(6131):616–619. doi: 10.1038/328616a0. [DOI] [PubMed] [Google Scholar]
  20. Stewart G. D., Bruns G. A., Wasmuth J. J., Kurnit D. M. An anonymous DNA segment (II227) maps to the long arm of human chromosome 5 and identifies a BstXI polymorphism (D5S26). Nucleic Acids Res. 1987 May 11;15(9):3939–3939. doi: 10.1093/nar/15.9.3939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Søndergaard J. O., Svendsen L. B., Witt I. N., Bülow S., Lauritsen K. B., Tetens G. Mandibular osteomas in the cancer family syndrome. Br J Cancer. 1985 Dec;52(6):941–943. doi: 10.1038/bjc.1985.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tops C. M., Wijnen J. T., Griffioen G., von Leeuwen I. S., Vasen H. F., den Hartog Jager F. C., Breukel C., Nagengast F. M., van der Klift H. M., Lamers C. B. Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers. Lancet. 1989 Dec 9;2(8676):1361–1363. doi: 10.1016/s0140-6736(89)91968-5. [DOI] [PubMed] [Google Scholar]
  23. Varesco L., Thomas H. J., Cottrell S., Murday V., Fennell S. J., Williams S., Searle S., Sheer D., Bodmer W. F., Frischauf A. M. CpG island clones from a deletion encompassing the gene for adenomatous polyposis coli. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10118–10122. doi: 10.1073/pnas.86.24.10118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  25. WOOLF C. M. A genetic study of carcinoma of the large intestine. Am J Hum Genet. 1958 Mar;10(1):42–47. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES