Skip to main content
SpringerLink
Log in

Mapping eight new polymorphisms in 11q13 in the vicinity of multiple endocrine neoplasia type 1: identification of a new distal recombinant

  • Review Article
  • Published:
Human Genetics Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that predisposes affected individuals to neoplasms of the parathyroid glands, endocrine pancreas, anterior pituitary, and carcinoids. The MEN1 locus has been localized by family studies to 11q13, flanked by markers PGA and D11S97. Eight new polymorphisms located in three separate radiation-reduced somatic cell hybrid segregation groups were developed. The order of the new markers, within the context of previously described loci, was determined by linkage analysis on the Venezuelan reference pedigree. Four independent MEN1 families, consisting of 57 affected individuals, and 70 individuals at-risk for the disease were genotyped. Sixteen people inherited a chromosome that shows recombination between a linked marker and the disease. The nearest proximal and distal markers that show recombination with the disease are D11S822 and GSTP1, respectively, thereby narrowing the candidate region for MEN1 by 50% on the distal side. Using these loci in haplotype analysis, an accurate presymptomatic molecular diagnostic test has been developed. These new markers in 11q13 linked to MEN1 also facilitate the genetic and physical characterization of this very gene-rich region.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bale AE, Norton JA, Wong EL, Fryburg JS, Maton PN, Oldfield EH, Streeten E, Aurbach GD, Brandi ML, Friedman E, Spiegel AM, Taggart RT, Marx SJ (1991) Allelic loss on chromosome 11 in hereditary and sporadic tumors related to familial multiple endocrine neoplasia type 1. Cancer Res 51:1154–1157

    Google Scholar 

  • Bale SJ, Bale AE, Stewart K, Dachowski L. McBride OW, Glaser T, Green JE, Mulvihill JJ, Brandi M, Sakaguchi K, et al (1989) Linkage analysis of multiple endocrine neoplasia type 1 with INT2 and other markers on chromosome 11. Genomics 4:320–322

    Google Scholar 

  • Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331

    Google Scholar 

  • Brandi ML, Weber G, Svensson A, Falchett A, Tonelli F, Catello R, Furlani L, Scappaticci S, Fraccaro M, Larsson C (1993) Homozygotes for the autosomal dominant neoplasia syndrome (MEN1). Am J Hum Genet 53:1167–1172

    Google Scholar 

  • Browne DL, Gault J, Thompson MB, Hauge XY, Evans GA, Litt M (1991) Dinucleotide repeat polymorphism at the D11S527 locus. Nucleic Acids Res 19:4790

    Google Scholar 

  • Bystrom C, Larsson C, Blomberg C, Sandelin K, Falkmer U, Skogseid B, Oberg K, Werner S, Nordenskjold M (1990) Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. Proc Natl Acad Sci USA 87:1968–1972

    Google Scholar 

  • Call KM, Glaser T, Ito CY, Bucker AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60:509–520

    Google Scholar 

  • Casey G, Smith R, McGillivray D, Peters G, Dickson C (1986) Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene. Mol Cell Biol 6:502–510

    Google Scholar 

  • Cooperative Human Linkage Center, (CHLC): Murray JC et al (1994) A comprehensive human linkage map with centimorgan density. Science 265:2049–2054

    Google Scholar 

  • Cutler RE, Reiss E, Ackermann LA (1964) Familial hyperparathyroidism: a kindred involving eleven cases with a discussion of primary chief-cell hyperplasia. N Engl J Med 270:859–865

    Google Scholar 

  • Feinberg AP, Vogelstein B (1983) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13

    Google Scholar 

  • Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093

    Google Scholar 

  • Forsman K, Graff C, Nordstrom S, Johansson K, Westermark E, Lundgren E, Gustavson K-H, Wadelius C, Holmgren G (1992) The gene for Best's macular dystrophy is located at 11q13 in a Swedish family. Clin Genet 42:156–159

    Google Scholar 

  • Foroud T, Wei S, Ziv Y, Sobel E, Lange E, Chao A, Goradia T, Huo Y et al (1991) Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium. Am J Hum Genet 49:1263–1279

    Google Scholar 

  • Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323:543–636

    Google Scholar 

  • Fujimori M, Wells SA Jr, Nakamura Y (1992) Fine-scale mapping of the gene responsible for multiple endocrine neoplasia type 1 (MEN1). Am J Hum Genet 50:399–403

    Google Scholar 

  • Gerhard DS, Lawrence E, Wu J, Chua H, Ma N, Bland S, Jones C (1992) Isolation of 1001 new markers from human chromosome 11, excluding the region of 11p13–p15. 5, and their sublocalization by a new series of radiation-reduced somatic cell hybrids. Genomics 13:1133–1142

    Google Scholar 

  • Goldsmith RE, Sizemore GW, Chen I-W, Zalme E, Altemeier A (1976) Familial hyperparathyroidism: description of a large kindred with physiologic observations and a review of the literature. Ann Intern Med 84:36–43

    Google Scholar 

  • Gyapay G, Morisette J, Vignal A, Dib C et al (1994) The 1993–94 Genethon human linkage map. Nat Genet 7 [Suppl]:246–339

    Google Scholar 

  • Haines JL, Trofatter JA, Tanzi RE, Watkins P, Wexler NS, Conneally PM, Gusella JF (1992) Chromosome 21 genetic linkage data set based on the Venezuelan reference pedigree. Cytogenet Cell Genet 59:88–89

    Google Scholar 

  • Iwasaki H, Stewart PW, Dilley WG, Holt MS, Steinbrueck TD, Wells SA, Donis-Keller H (1992) A minisatellite and a microsatellite polymorphism within 1. 5 kb at the human muscle glycogen phosphorylase (PYGM) locus can be amplified by PCR and have combined informativeness of PIC 0. 95. Genomics 13:7–15

    Google Scholar 

  • Janson M, Larsson C, Werelius B, Jones C, Glaser T, Nakamura Y, Jones CP, Nordenskjold M (1991) Detailed physical map of human chromosomal region 11q12–13 shows high meiotic recombination rate around the MEN 1 locus. Proc Natl Acad Sci USA 88:10609–10613

    Google Scholar 

  • Julier C, Nakamura Y, Lathrop M, O'Connell P, Lepper M, Litt M, Mohandas T, Lalouel J, White R (1990) A detailed genetic map of the long arm of chromosome 11. Genomics 7:335–345

    Google Scholar 

  • Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stocker E, Day KH III, Johnson BE, Skolnick MH (1994) A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440

    Google Scholar 

  • Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823

    Google Scholar 

  • Lander ES, Green P (1987) Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci USA 84:2363–2367

    Google Scholar 

  • Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85–87

    Google Scholar 

  • Larsson C, Weber G, Kvanta E, Lewis K, Janson M, Jones C, Glaser T, Evans G, Nordenskjold M (1992a) Isolation and mapping of polymorphic cosmid clones used for sublocalization of the multiple endocrine neoplasia type 1 (MEN1) locus. Hum Genet 89:187–193

    Google Scholar 

  • Larsson C, Shepherd J, Nakamura Y, Blomber C, Weber G, Werelius B, Hayward N, Teh B, Tokino T, Seizinger B, Skogseid B, Oberg K, Nordenskjold M (1992b) Predictive testing for multiple endocrine neoplasia type 1 using DNA polymorphisms. J Clin Invest 89:1344–1349

    Google Scholar 

  • Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446

    Google Scholar 

  • Leppert M, Baird L, Anderson K, Otterud B, Lupski JR, Lewis RA (1994) Bardet-Biedl syndrome is linked to DNA markers on chromosome 11q and is genetically heterogeneous. Nat Genet 7:108–112

    Google Scholar 

  • Li Y, Muller B, Fuhrman C, Nouhuys EC van, Laqua H, Humphries P, Scwinger E, Gal A (1992) The autosomal dominant familial exudative vitreoretinopathy locus maps on 11q and is closely linked to D11S533. Am J Hum Genet 51:749–754

    Google Scholar 

  • Litt M, Kramer P, Hauge XY, Weber JL, Wang Z, Wilkie PJ, Holt MS, Mishra S, Donis-Keller H, Warnich L, Retief AE, Jones C, Weissenbach J (1993) A microsatellite-based index map of human chromosome 11. Hum Mol Genet 2:909–913

    Google Scholar 

  • Maslen C, Jones C, Glaser T, Sheehy R, Magenis RE, Kellogg J, Litt M (1987) Seven polymorphic loci mapping to human chromosomal region 11q22-qter. Cytogenet Cell Genet 46:656

    Google Scholar 

  • Moffatt MF (1993) Dinucleotide repeat polymorphism at the D11S480 locus. Hum Mol Genet 2:492

    Google Scholar 

  • Murray JC, Buetow KH, Weber JL, Ludigsen S, Scherpbier-Heddema T, Manion F, Quillen J, Sheffield VC, Sunden S, Duyk GM (1994) A comprehensive human linkage map with centimorgan density. Science 265:2049–2054

    Google Scholar 

  • Nakamura Y, Larsson C, Julier C, Bystrom C, Skogseid B, Wells S, Oberg K, Carlson M, Taggart T, O'Connell P, Leppert M, Lalouel J-M, Nordenskjold M, White R (1989) Localization of the genetic defect in multiple endocrine neoplasia type 1 within a small region of chromosome 11. Am J Hum Genet 44:751–755

    Google Scholar 

  • Nobori T, Miura K, Wu DJ, Lois A, Takabayash K, Carson DA (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368:753–756

    Google Scholar 

  • Polymeropoulos MH, Xiao H, Rath DS, Merril CR (1991) Dinucleotide repeat polymorphism at the int-2 proto-oncogene locus (INT2). Nucleic Acids Res 18:1468

    Google Scholar 

  • Radford DM, Ashley SW, Wells SA Jr, Gerhard DS (1990) Loss of heterozygosity of markers on chromosome 11 in tumors from patients with multiple endocrine neoplasia syndrome type 1. Cancer Res 50:6529–6533

    Google Scholar 

  • Smith CM, Bora PS, Bora NS, Jones C, Gerhard DS (1995) Genetic and radiation-reduced somatic cell hybrid sublocalization of the human GSTP1 gene. Cytogen Cell Genet (in press)

  • Stafford AN, Rider SH, Hopkin JM, Cookson WO, Monaco AP (1994) A 2. 8 Mb YAC contig in 11q12–q13 localizes candidate genes for atopy: FceRIβ and CD20. Hum Mol Genet 3:779–785

    Google Scholar 

  • Stone EM, Nichols BE, Streb LM, Kumura AE, Sheffield VC (1992 a) Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. Nat Genet 1:246–250

    Google Scholar 

  • Stone EM, Kimura AE, Folk JC, Bennett SR, Nichols BE, Streb LM, Sheffield VC (1992b) Genetic linkage of autosomal dominant neovascular inflammatory vitreoretinopathy to chromosome 11q13. Hum Mol Genet 1:685–689

    Google Scholar 

  • Taggart RT, Mohandas TK, Shows TB, Bell GI (1985) Variable numbers of pepsinogen genes are located in the centromeric region of human chromosome 11 and determine the high-frequency electrophoretic polymorphism. Proc Natl Acad Sci USA 82:6240–6244

    Google Scholar 

  • Tanigami A, Tokino T, Takita K-I, Takiguchi S, Nakamura Y (1992) A 14-Mb physical map of the region at chromosome 11q13 harboring the MEN1 locus and the tumor amplicon region. Genomics 13:16–20

    Google Scholar 

  • Tedder TF, Streuli M, Schlossman SF, Saito H (1988) Isolation and structure of a cDNA encoding the B1(CD20) cell-surface antigen of human B lymphocytes. Proc Natl Acad Sci USA 85:208–212

    Google Scholar 

  • Thakker RV, Bouloux P, Wooding C, Chotai K, Borad PM, Spurr NK, Besser GM, O'Riorday JLH (1989) Association of tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N Engl J Med 321:218–224

    Google Scholar 

  • Thakker RV, Wooding C, Pang JT, Farren B, Harding B, Anderson DC, Besser GM, Bouloux P, Brenton DP, Buchanan KD, Edwards CR, Heath DA, Jackson CE, et al (1993) Linkage analysis of 7 polymorphic markers at chromosome 11q11. 2–11q13 in 27 multiple endocrine neoplasia type I families. Ann Hum Genet 57:17–25

    Google Scholar 

  • Young RP, Sharp PA, Lynch JR, Faux JA, Lathrop GM, Cookson WOCM, Hopkin JM (1992) Confirmation of genetic linkage between atopic IgE responses and chromosome 11q13. J Med Genet 29:236–238

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics, Washington University School of Medicine, 63 110, St. Louis, MO, USA

    Carissa M. Smith & Daniela S. Gerhard

  2. Department of Surgery, Washington University School of Medicine, 63 110, St. Louis, MO, USA

    Samuel A. Wells

Authors
  1. Carissa M. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samuel A. Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela S. Gerhard
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, C.M., Wells, S.A. & Gerhard, D.S. Mapping eight new polymorphisms in 11q13 in the vicinity of multiple endocrine neoplasia type 1: identification of a new distal recombinant. Hum Genet 96, 377–387 (1995). https://doi.org/10.1007/BF00191793

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00191793

Keywords

Search

Navigation