Detection of mutations in health care: Strategy for retinoblastoma
- Univ. of Toronto and Visible Genetics, Inc., Ontario (Canada); and others
For diseases such as retinoblastoma, diagnosis of germline mutations in the RB1 gene is the only effective way to predict which members of a family will develop tumors, since each family has its own unique mutation. In order to develop a routine clinical test for mutation identification, we are using retinoblastoma as a model system for three reasons: the genetics of retinoblastoma are well understood; most of the heritable retinoblastomas are caused by new germline mutations; and the consequences of mutation identification and carrier status are clear. The mutations responsible for retinoblastoma fall into three broad classes: deletions, insertions and/or rearrangements, missense or nonsense point mutations, and translocations. Each class requires a different detection technique. Initial screening by quantitative amplification of each exon detects large and small deletions and insertions. Samples for which all exons appear normal are then directly sequenced. Samples that still appear to be normal are studied by FISH with probes flanking RB1 in order to detect translocations. Data analysis, lab coordination and patient reporting are managed using new software to efficiently handle the large amounts of data collected. The software techniques and strategy for mutation identification will be applicable to any genetic disease locus with a high proportion of new mutations, for example other tumor suppressor loci.
- OSTI ID:
- 133491
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0219
- 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
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Related Subjects
BASIC STUDIES
99 MATHEMATICS
COMPUTERS
INFORMATION SCIENCE
MANAGEMENT
LAW
MISCELLANEOUS
SENSE ORGANS DISEASES
DIAGNOSIS
PATIENTS
GENES
GENE MUTATIONS
TRANSCRIPTION
GENE AMPLIFICATION
HUMAN CHROMOSOMES
CHROMOSOMAL ABERRATIONS
DETECTION
DATA PROCESSING
COMPUTER CODES
RETINA
DNA SEQUENCING
DNA HYBRIDIZATION
FLUORESCENCE
PROBES