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Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1

Published online by Cambridge University Press:  01 July 1997

D. HUMPHREY
Affiliation:
Experimental Medicine Division, Brigham and Women's Hospital, 221 Longwood Ave. Boston, MA 02115
J. KWIATKOWSKA
Affiliation:
Experimental Medicine Division, Brigham and Women's Hospital, 221 Longwood Ave. Boston, MA 02115
E. P. HENSKE
Affiliation:
Experimental Medicine Division, Brigham and Women's Hospital, 221 Longwood Ave. Boston, MA 02115
J. L. HAINES
Affiliation:
Neurogenetics Unit, Massachusetts General Hospital, Boston, MA 02114
D. HALLEY
Affiliation:
Department of Clinical Genetics, Erasmus University Rotterdam and Academic Hospital, Rotterdam, the Netherlands
M. van SLEGTENHORST
Affiliation:
Department of Clinical Genetics, Erasmus University Rotterdam and Academic Hospital, Rotterdam, the Netherlands
D. J. KWIATKOWSKI
Affiliation:
Experimental Medicine Division, Brigham and Women's Hospital, 221 Longwood Ave. Boston, MA 02115
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Abstract

RALGDS is a 115 kDa protein which was identified by its ability to enhance guanine nucleotide exchange for the ras family member ral. It also binds to activated ras and rap1, and appears to function as part of a signalling complex in downstream events following rap1 activation. Here we report the identification of full-length cDNA clones for human RALGDS, isolated from a brain cDNA library. The predicted protein has strong sequence homology to rat and murine isoforms of RALGDS in the N- and C-terminal regions, but an internal region (aa 250–380) shows relatively high divergence with only 42% identical amino acid residues. The human RALGDS gene is contained within a 30 kb region of 9q34, approximately 200 kb proximal to the ABO gene, within the current critical region for the tuberous sclerosis gene TSC1. Partial genomic structure was determined; it consists of at least 11 exons. Based upon analysis of Southern blots from 110 TSC patients, genomic DNA SSCP analysis, and RT-PCR analysis which demonstrated RNA expression of both alleles in patients from 9q34-linked TSC families using intragenic polymorphisms, we conclude that RALGDS is not likely to be TSC1.

Type
Research Article
Copyright
© University College London 1997

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