Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1992 Feb;29(2):75–80. doi: 10.1136/jmg.29.2.75

A linkage map of 10 loci flanking the Marfan syndrome locus on 15q: results of an International Consortium study.

M Sarfarazi 1, P Tsipouras 1, R Del Mastro 1, M Kilpatrick 1, P Farndon 1, M Boxer 1, A Bridges 1, C Boileau 1, C Junien 1, C Hayward 1, et al.
PMCID: PMC1015843  PMID: 1613769

Abstract

Members of an International Consortium for Linkage Analysis of the Marfan Syndrome (MFS1) have pooled data for joint analysis in an attempt to determine the precise location of the MFS1 gene and the order of 10 DNA markers on 15q. Five laboratories performed a total of 2111 genotypes in 22 families consisting of 225 affected and 248 normal subjects. For each marker a mean of 98 meioses was informative. D15S48 and D15S1 were identified as the closest linked markers with 99% upper confidence intervals of 12% and 13% respectively. We have used the CRI-MAP program to construct the most likely order as: D15S24-D15S25-D15S1-MFS1-D15S48-D15S49+ ++-(D15S45/S51)-(D15S29/S38). Placement of D15S2 in relation to -D15S1-D15S48- cannot be determined with certainty. The genetic map of these markers extends 53.6 cM in males and 65.0 cM in females with a sex averaged map of 60.7 cM. The sex difference was statistically significant (p = 0.005). Linkage heterogeneity between 22 MFS1 families was documented (p = 0.009) necessitating the exclusion of one family from the analysis. However, comparison of the remaining 21 families for two point and multipoint lod scores showed no evidence for linkage heterogeneity of the MFS1 locus.

Full text

PDF
78

Selected References

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

  1. Barker D., Schafer M., White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell. 1984 Jan;36(1):131–138. doi: 10.1016/0092-8674(84)90081-3. [DOI] [PubMed] [Google Scholar]
  2. Beighton P., de Paepe A., Danks D., Finidori G., Gedde-Dahl T., Goodman R., Hall J. G., Hollister D. W., Horton W., McKusick V. A. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581–594. doi: 10.1002/ajmg.1320290316. [DOI] [PubMed] [Google Scholar]
  3. Blanton S. H., Sarfarazi M., Eiberg H., de Groote J., Farndon P. A., Kilpatrick M. W., Child A. H., Pope F. M., Peltonen L., Francomano C. A. An exclusion map of Marfan syndrome. J Med Genet. 1990 Feb;27(2):73–77. doi: 10.1136/jmg.27.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boileau C., Jondeau G., Bonaiti C., Coulon M., Delorme G., Dubourg O., Bourdarias J. P., Junien C. Linkage analysis of five fibrillar collagen loci in a large French Marfan syndrome family. J Med Genet. 1990 Feb;27(2):78–81. doi: 10.1136/jmg.27.2.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brissenden J. E., Page D. C., de Martinville B., Trowsdale J., Botstein D., Francke U. Regional assignments of three polymorphic DNA segments on human chromosome 15. Genet Epidemiol. 1986;3(4):231–239. doi: 10.1002/gepi.1370030404. [DOI] [PubMed] [Google Scholar]
  6. Dausset J. Le centre d'étude du polymorphisme humain. Presse Med. 1986 Oct 18;15(36):1801–1802. [PubMed] [Google Scholar]
  7. Dietz H. C., Cutting G. R., Pyeritz R. E., Maslen C. L., Sakai L. Y., Corson G. M., Puffenberger E. G., Hamosh A., Nanthakumar E. J., Curristin S. M. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337–339. doi: 10.1038/352337a0. [DOI] [PubMed] [Google Scholar]
  8. Dietz H. C., Pyeritz R. E., Hall B. D., Cadle R. G., Hamosh A., Schwartz J., Meyers D. A., Francomano C. A. The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics. 1991 Feb;9(2):355–361. doi: 10.1016/0888-7543(91)90264-f. [DOI] [PubMed] [Google Scholar]
  9. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  10. Fujimoto E., Nakamura Y., Ballard L., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pEFD49.2) on chromosome 15. Nucleic Acids Res. 1988 Nov 25;16(22):10943–10943. doi: 10.1093/nar/16.22.10943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujimoto E., Nakamura Y., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pEFD49.3) on chromosome 15. Nucleic Acids Res. 1988 Nov 25;16(22):10944–10944. doi: 10.1093/nar/16.22.10944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fujimoto E., Nakamura Y., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pEFZ33) on chromosome 15. Nucleic Acids Res. 1988 Nov 25;16(22):10946–10946. doi: 10.1093/nar/16.22.10946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kainulainen K., Pulkkinen L., Savolainen A., Kaitila I., Peltonen L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990 Oct 4;323(14):935–939. doi: 10.1056/NEJM199010043231402. [DOI] [PubMed] [Google Scholar]
  14. Keats B. J., Sherman S. L., Morton N. E., Robson E. B., Buetow K. H., Cartwright P. E., Chakravarti A., Francke U., Green P. P., Ott J. Guidelines for human linkage maps: an international system for human linkage maps (ISLM, 1990). Genomics. 1991 Mar;9(3):557–560. doi: 10.1016/0888-7543(91)90426-f. [DOI] [PubMed] [Google Scholar]
  15. Lander E. S., Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. doi: 10.1073/pnas.84.8.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lee B., Godfrey M., Vitale E., Hori H., Mattei M. G., Sarfarazi M., Tsipouras P., Ramirez F., Hollister D. W. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991 Jul 25;352(6333):330–334. doi: 10.1038/352330a0. [DOI] [PubMed] [Google Scholar]
  17. Nakamura Y., Lathrop M., O'Connell P., Leppert M., Lalouel J. M., White R. A mapped set of DNA markers for human chromosome 15. Genomics. 1988 Nov;3(4):342–346. doi: 10.1016/0888-7543(88)90125-5. [DOI] [PubMed] [Google Scholar]
  18. Ott J. Linkage analysis and family classification under heterogeneity. Ann Hum Genet. 1983 Oct;47(Pt 4):311–320. doi: 10.1111/j.1469-1809.1983.tb01001.x. [DOI] [PubMed] [Google Scholar]
  19. Pyeritz R. E., McKusick V. A. The Marfan syndrome: diagnosis and management. N Engl J Med. 1979 Apr 5;300(14):772–777. doi: 10.1056/NEJM197904053001406. [DOI] [PubMed] [Google Scholar]
  20. Tsipouras P. A workshop on Marfan syndrome, 10 June 1989, Farmington, CT, USA. J Med Genet. 1990 Feb;27(2):139–140. doi: 10.1136/jmg.27.2.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tsipouras P., Sarfarazi M., Devi A., Weiffenbach B., Boxer M. Marfan syndrome is closely linked to a marker on chromosome 15q1.5----q2.1. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4486–4488. doi: 10.1073/pnas.88.10.4486. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES