Cloning and characterization of tuberous sclerosis determining genes on 9q and 16p
- Erasmus Univ., Rotterdam (Netherlands); and others
Tuberous sclerosis (TSC) is an autosomal dominant multisystem disorder, characterized by the widespread development of hamartomata. TSC is genetically heterogeneous, with trait causing loci on 9q34 and 16p13.3. Last year the TSC2 gene on 16p13.3 has been identified by the European Chromosome 16 TSC Consortium. The TSC2 gene acts as a tumour suppressor gene and encodes a 198 kD protein (tuberin) with a small region of homology to the rap1-GTPase-activating-protein. Allowing for heterogeneity, we have performed a linkage analysis on 14 Dutch and British families. Combined analysis (ICA) of both chromosomal regions revealed an overall lod score (under heterogeneity) of 8.92. We assigned the TSC1 locus to a region in between the Abelson oncogene and the ABO bloodgroup locus. On chromosome 16 the peak lod score was obtained at marker 16AC2.5. This finding confirms the accuracy of the imaginary chromosome approach (ICA), since 16AC2.5 is known to be at less than 200 kb from TSC2. The proportion of ABO linked families (TSC1) was estimated to be 65%. In the ABO region we have mapped about 200 cosmids in 6 contigs ranging from 40 to more than 300 kb. With respect to TSC2 we focused on the construction of a full length cDNA clone and the generation of antibodies against fusion proteins and synthetic peptides. These are being utilized in studies on the cellular localization, the tissue distribution and the normal and impaired function of tuberin.
- OSTI ID:
- 134025
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0761
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Molecular analysis of tuberous sclerosis complex (TSC1) on chromosome 9q34
Hamartomas from patients with tuberous sclerosis show loss of heterozygosity for chromosome 9q34