Elsevier

Genomics

Volume 11, Issue 4, December 1991, Pages 931-940
Genomics

Regular article
cDNA cloning of the type 1 neurofibromatosis gene: Complete sequence of the NF1 gene product

https://doi.org/10.1016/0888-7543(91)90017-9Get rights and content

Abstract

Von Recklinghausen neurofibromatosis, or type 1 neurofibromatosis (NF1), is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the embryonic neural crest. Portions of the gene have been recently identified by positional cloning, and sequence analysis has shown homology to the GTPase activating protein (GAP) family. In this report we present the results of an extensive cDNA walk resulting in the cloning of the complete coding region of the NF1 transcript. Analysis of the sequences reveals an open reading frame of 2818 amino acids, although alternatively spliced products may code for different protein isoforms. The gene extends for approximately 300 kb on chromosome 17, with its promoter in a CpG-rich island.

References (65)

  • P. Klein et al.

    The detection and classification of membrane-spanning proteins

    Biochim. Biophys. Acta

    (1985)
  • M. Koenig et al.

    Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals

    Cell

    (1987)
  • G.A. Martin et al.

    The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21

    Cell

    (1990)
  • P. O'Connell et al.

    The human homolog of murine Evi-2 lies between two von Recklinghausen neurofibromatosis translocations

    Genomics

    (1990)
  • M. Otsu et al.

    Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60 c-src complexes, and P13 kinase

    Cell

    (1991)
  • B. Rubinfeld et al.

    Molecular cloning of a GTPase activating protein specific for the Krev-1 protein p21rap1

    Cell

    (1991)
  • D. Viskochil et al.

    Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus

    Cell

    (1990)
  • G. Xu et al.

    The neurofibromatosis type 1 gene encodes a protein related to GAP

    Cell

    (1990)
  • G. Xu et al.

    The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae

    Cell

    (1990)
  • H. Adari et al.

    Guanosine triphosphate activating protein (GAP) interacts with the p21 ras effector binding domain

    Science

    (1988)
  • W.D. Benton et al.

    Screening lambdagt recombinant clones by hybridization to single plaques in situ

    Science

    (1977)
  • G. Bollag et al.

    Differential regulation of rasGAP and neurofibromatosis gene product activities

    Nature

    (1991)
  • A. Buchberg et al.

    Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway

    Nature

    (1990)
  • C. Cales et al.

    The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product

    Nature

    (1988)
  • T.E. Carey et al.

    Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells

  • F. Crowe et al.
  • J. Devereux et al.

    A comprehensive set of sequence analysis programs for the VAX

    Nucleic Acids Res

    (1984)
  • D. Diekmann et al.

    Bcr encodes a GTPase-activating protein for p21 ras

    Nature

    (1991)
  • J.W. Fountain et al.

    Physical mapping of the von Recklinghausen neurofibromatosis region on chromosome 17

    Am. J. Hum. Genet

    (1989)
  • J.W. Fountain et al.

    Physical mapping of a translocation breakpoint in neurofibromatosis

    Science

    (1989)
  • D. Ginsburg et al.

    Human von Willebrand factro (VWF): Isolation of cDNA clones and chromosomal localization

    Science

    (1985)
  • T.W. Glover et al.

    Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis

    Genes Chrom. Cancer

    (1991)
  • Cited by (379)

    View all citing articles on Scopus
    View full text