DNA segment in chromosome 9q34 which is duplicated in a sporadic case of Tuberous sclerosis encodes a new gene with homology to oncogenes in the Ras signaling pathway
- Univ. of California, Irvine, CA (United States); and others
The TSC1 gene has been mapped to a 1 megabase region on chromosome 9q34. This region is flanked by markers D9S125 and D9S114. D9S10 and D9S66 loci map within this region. In a sporadic case of Tuberous sclerosis we demonstrated the presence of a DNA duplication using probes for the D9S10, and D9S66 loci and cosmids which overlap the telomeric end of the D9S66 cosmid. The duplication was demonstrated by analysis of the D9S66 polymorphism which revealed the presence of two maternal alleles in the patient. It was also demonstrated using FISH to analyze metaphase and interphase chromosomes, and by pulsed field gel electrophoresis which revealed novel M1u1 fragments in patient cellular DNA examined using as probes unique sequence regions of D9S10, or unique sequence regions of cosmids flanking the telomeric end of D9S66. There was no evidence for duplication of DBH or ABL. We carried out DNA sequence analysis of regions of D9S10 and cosmids which overlap D9S10 at its telomeric end, and determined that these cosmids contain exons with regions of high homology to portions of the Vav oncogene. We used a unique sequence region of D9S10 to examine mRNA and demonstrated a transcript of 4 kb. These studies are important since they have refined the map position of the TSC1 locus and secondly because they have led to the identification of a new oncogene with high homology to oncogenes in the RAS signalling pathway.
- OSTI ID:
- 133390
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0118
- 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
Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1
Mapping cosmid contigs to intervals on chromosome 9q34 by FISH