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Genetic Heterogeneity in Tuberous Sclerosis. Study of a Large Collaborative Dataset
- Source :
- Annals of the New York Academy of Sciences. 615:256-264
- Publication Year :
- 1991
- Publisher :
- Wiley, 1991.
-
Abstract
- Tuberous sclerosis (TSC) is a multisystem autosomal dominant hamartosis whose genetics is complicated by reduced penetrance and widely varying clinical expression. Results of linkage analyses have variously suggested two different locations for a TSC gene. A collaborative dataset has been assembled to clarify the issue of genetic heterogeneity. We have now analyzed the data from a combined sample of 111 families. Using Ott's HOMOG programs, we completed three tests of homogeneity: (1) for chromosome 9q, (2) for chromosome 11q, and (3) for the combined 9q and 11q data. For test 1 the chi-square (1 df) was 21.54 (p less than 0.001), for test 2 the chi-square (1 df) was 0.13 (p greater than 0.35), and for test 3 the chi-square (2 df) was 37.61 (p less than 0.0001). Additionally, we examined the combined data for evidence that a third, as yet unlinked locus exists. Results of this last test were suggestive but not significant. Clearly loci for TSC are present on both chromosomes 9q and 11q. The maximum likelihood estimate of the proportion of chromosome 9q-linked families is 0.38, for chromosome 11q-linked families is 0.47, and for the unlinked type 0.15. Alternative explanations for these latter families include chance sampling of recombinants, nongenetic phenocopies, or misclassification.
- Subjects :
- Genetics
Phenocopy
Likelihood Functions
Genetic Linkage
Genetic heterogeneity
Chromosomes, Human, Pair 11
General Neuroscience
Chromosome
Locus (genetics)
Biology
medicine.disease
Penetrance
General Biochemistry, Genetics and Molecular Biology
Tuberous sclerosis
History and Philosophy of Science
Tuberous Sclerosis
Genetic linkage
medicine
Humans
Chromosomes, Human, Pair 9
Gene
Polymorphism, Restriction Fragment Length
Genes, Dominant
Subjects
Details
- ISSN :
- 17496632 and 00778923
- Volume :
- 615
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi.dedup.....59598e26f3715c00a925397f3e8deee4