Detection of mutations in health care: Strategy for retinoblastoma

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133491

Dunn, J M; Du, D; Mostachfi, H ^[1]

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1. 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--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
CHROMOSOMAL ABERRATIONS
COMPUTER CODES
DATA PROCESSING
DETECTION
DIAGNOSIS
DNA HYBRIDIZATION
DNA SEQUENCING
FLUORESCENCE
GENE AMPLIFICATION
GENE MUTATIONS
GENES
HUMAN CHROMOSOMES
PATIENTS
PROBES
RETINA
SENSE ORGANS DISEASES
TRANSCRIPTION