Professor Duncan Bassett

Höppener JW, De Wit MJ, Simarro-Doorten AY, Roijers JF, van Herrewaarden HM, Lips CJ, Parente F, Quincey D, Gaudray P, Khodaei S, Weber G, Teh B, Farnebo F, Larsson C, Zhang CX, Calender A, Pannett AAJ, Forbes SA, Bassett JHD, Thakker RV, Lemmens I, Van de Ven WJ, Kas Ket al., 1998, A putative human zinc-finger gene (ZFPL1) on 11q13, highly conserved in the mouse and expressed in exocrine pancreas. The European Consortium on MEN 1, Genomics, Vol: 50, Pages: 251-259

In the process of identification of the multiple endocrine neoplasia type 1 gene, which was recently published, we isolated a novel gene in the 11q13 region. This gene (named ZFPL1, for zinc-finger protein-like 1) is expressed strongly in the exocrine pancreas as a 1.4-kb polyadenylated RNA encoding a putative protein of 310 amino acids. A mouse EST contig predicts an equally sized murine protein with 91% amino acid sequence identity to the human protein. No significant homology with known proteins could be found through database screening. However, zinc-finger-like domains and leucine-zipper-like motifs in the predicted ZFPL1 protein were identified, suggesting the presence of DNA-binding and dimerization domains possibly involved in transcription regulation. This notion is supported by the presence of a putative bipartite nuclear localization signal. This paper presents the full-length cDNA sequence for this gene, its genomic structure and chromosomal orientation, and expression studies by Northern blot hybridization and RNA in situ hybridization.

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, 1998, The search for the MEN1 gene. The European Consortium on MEN-1., J Intern Med, Vol: 243, Pages: 441-446, ISSN: 0954-6820

The search for the gene whose mutations predispose individuals to multiple endocrine neoplasia type 1 (MEN-1) started in 1988 when the MEN1 locus was assigned to 11q13, close to PYGM. It came to an end with the recent identification of a gene expressed ubiquitously which harbours inactivating mutations associated with MEN-1. During these nine years, the genetic linkage interval had been slowly reduced, and losses of heterozygosity (LOH) in MEN-1 tumours had given strong indications that MEN1 was a tumour suppressor gene. It is ironic that MEN1 was finally found to be located less than 100 kb telomeric to PYGM. From the beginning, this gene was the most tightly linked genetically to MEN-1. In addition, LOH had already shown (in 1990) that it was the most likely centromeric boundary of the MEN1 minimal region. We recently narrowed the critical region to 900 kb through meiotic mapping, and established a 1200-kb sequence-ready contig consisting of cosmids, bacterial artificial chromosomes (BACs) and P1-derived artificial chromosomes (PACs), including three gene clusters (19 genes and 3 expressed sequence tags). Taking LOH results into account, the gene was likely to be present in the 300-kb area telomeric to PYGM that we had covered with BACs. One of the novel genes that we have identified by cDNA selection in this region, SCG2 (Suppressor Candidate Gene 2), proved to be identical to the recently published MEN1 gene. Mutation analysis of SCG2 in 11 unrelated MEN-1 families identified one nucleotide sequence polymorphism and 10 different mutations that segregated with the disease.

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Lemmes I, Van de Ven WJM, Kas K, Zhang CX, Giraud S, Wautot V, Buisson N, Pugeat M, Peix JL, Caldener A, Parente F, Quincey D, Courseaux A, Carle GF, Gaudray P, De Wit MJ, Lips CJM, Höppener JWM, Khodaei S, Grant AL, Weber G, Teh BT, Farnebo F, Kytölä S, Grimmond S, Phelan C, Larsson C, Bassett JHD, Forbes DA, Pannett AAJ, Thakker RVet al., 1998, The search for the <i>MEN1</i> gene, 6th International Workshop on Multiple Endocrine Neoplasia and von Hippel-Lindau Disease, Publisher: WILEY, Pages: 441-446, ISSN: 0954-6820

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• Citations: 3

Bassett JHD, Forbes SA, Pannett AAJ, Lloyd SE, Christie PT, Wooding C, Edwards CR, Monson JP, Sampson J, Wass JAH, Harding B, Besser GM, Wheeler MH, Thakker RVet al., 1998, Characterization of mutations in patients with multiple endocrine neoplasia type 1, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 62, Pages: 232-244, ISSN: 0002-9297

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• Citations: 317

Bassett JHD, Pannett AAJ, Forbes SA, Thakker RV, McCarthy M, Read AP, Teh BT, Larsson C, Kytola S, Leisti J, Salmela P, Weber G, Giraud S, Zhang CX, Calender A, Hoppener JWM, vanAmstel HKP, Lips CJM, Kas K, VandeVen WJM, Gaudray Pet al., 1997, The European Consortium on MEN1 - Linkage disequilibrium studies in multiple endocrine neoplasia type 1 (MEN1), HUMAN GENETICS, Vol: 100, Pages: 657-665, ISSN: 0340-6717

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• Citations: 9

Forbes SA, Pannett AAJ, Bassett JHD, Harding B, Wooding C, Thakker RV, Butler R, Ogilvie D, Anand R, Gaudray P, Weber G, Larsson C, Zhang CX, Calender A, Hoppener JWM, Lips CJM, Kas Ket al., 1997, Mapping of the gene encoding the B56 beta subunit of protein phosphatase 2A (PPP2R5B) to a 0.5-Mb region of chromosome 11q13 and its exclusion as a candidate gene for multiple endocrine neoplasia type 1 (MEN1), HUMAN GENETICS, Vol: 100, Pages: 481-485, ISSN: 0340-6717

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• Citations: 1

Lemmens I, Merregaert J, VandeVen WJM, Kas K, Zhang CX, Giraud S, Wautot V, Buisson N, DeWitte K, Salandre J, Lenoir G, Calender A, Parente F, Quincey D, Courseaux A, Carle GF, Gaudray P, DeWit MJ, Lips CJM, Hoppener JWM, Khodaei S, Grant AL, Weber G, Kytola S, Teh BT, Farnebo F, Grimmond S, Phelan C, Larsson C, Forbes SA, Bassett JHD, Pannett AAJ, Thakker RVet al., 1997, Construction of a 1.2-Mb sequence-ready contig of chromosome 11q13 encompassing the multiple endocrine neoplasia type 1 (MEN1) gene - The European consortium on type 1 (MEN1) gene, GENOMICS, Vol: 44, Pages: 94-100, ISSN: 0888-7543

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• Citations: 28

Lemmens I, VandeVen WJM, Kas K, Zhang CX, Giraud S, Wautot V, Buisson N, DeWitte K, Salandre J, Lenoir G, Pugeat M, Calender A, Parente F, Quincey D, Gaudray P, DeWit MJ, Lips CJM, Hoppener JWM, Khodaei S, Grant AL, Weber G, Kytola S, Teh BT, Farnebo F, Phelan C, Hayward N, Larsson C, Pannett AAJ, Forbes SA, Bassett JHD, Thakker RVet al., 1997, Identification of the multiple endocrine neoplasia type 1 (MEN1) gene, HUMAN MOLECULAR GENETICS, Vol: 6, Pages: 1177-1183, ISSN: 0964-6906

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• Citations: 483

Courseaux A, Grosgeorge J, Gaudray P, Pannett AAJ, Forbes SA, Williamson C, Bassett D, Thakker RV, Teh BT, Farnebo F, Shepherd J, Skogseid B, Larsson C, Giraud S, Zhang CX, Salandre J, Calender Aet al., 1996, Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13 - The European consortium on MEN1, GENOMICS, Vol: 37, Pages: 354-365, ISSN: 0888-7543

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• Citations: 84

Courseaux A, Grosgeorge J, Gaudray P, Pannett AAJ, Forbes SA, Williamson C, Bassett D, Thakker RV, Teh BT, Farnebo F, Shepherd J, Skogseid B, Larsson C, Giraud S, Zhang CX, Salandre J, Calender Aet al., 1996, Definition of the Minimal MEN1 Candidate Area Based on a 5-Mb Integrated Map of Proximal 11q13, Genomics, Vol: 37, Pages: 345-356

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449

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BASSETT JHD, THAKKER RV, 1995, MOLECULAR-GENETICS OF DISORDERS OF CALCIUM HOMEOSTASIS, BAILLIERES CLINICAL ENDOCRINOLOGY AND METABOLISM, Vol: 9, Pages: 581-608, ISSN: 0950-351X

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• Citations: 5

Bassett JHD, Thakker RV, 1995, Genetic and molecular biological aspects of endocrine disease, Genetic and molecular biological aspects of endocrine disease, Editors: Thakker, Pages: 581-608, ISBN: 9780702019456

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Hirst MC, Bassett JH, Roche A, Davies KEet al., 1992, Preparation of radiolabelled hybridization probes by STS labelling., Trends Genet, Vol: 8, Pages: 6-7, ISSN: 0168-9525

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Hirst MC, Bassett JHD, Roche A, Davies KEet al., 1992, Preparation of radiolabelled hybridisation probes by STS labelling, Trends in Genetics, Vol: 8, Pages: 5-6

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Hirst MC, Roche A, Flint TJ, Bassett JHD, Davies KEet al., 1991, Linear order of new and established DNA markers around the Fragile site at Xq27.3, Genomics, Vol: 10, Pages: 243-249

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