Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset

J. L. Haines, J. Amos, J. Attwood, N. T. Bech-Hansen, M. Burley, P. M. Conneally, J. M. Connor, R. Fahsold, P. Flodman, A. Fryer, D. J J Halley, A. Jewell, L. A J Janssen, R. Kandt, H. Northrup, J. Osborne, Margaret A Pericak-Vance, S. Povey, J. Sampson

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 of 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 < 0.001), for test 2 the chi-square (1 df) was 0.13 (p > 0.35), and for test 3 the chi-square (2 df) was 37.61 (p < 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.

Original languageEnglish
Pages (from-to)256-264
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume615
StatePublished - Sep 4 1991
Externally publishedYes

Fingerprint

Tuberous Sclerosis
Genetic Heterogeneity
Chromosomes
Chi-Square Distribution
Likelihood Functions
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 2
Penetrance
Maximum likelihood
Genes
Datasets
Chromosome
Sampling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Haines, J. L., Amos, J., Attwood, J., Bech-Hansen, N. T., Burley, M., Conneally, P. M., ... Sampson, J. (1991). Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset. Annals of the New York Academy of Sciences, 615, 256-264.

Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset. / Haines, J. L.; Amos, J.; Attwood, J.; Bech-Hansen, N. T.; Burley, M.; Conneally, P. M.; Connor, J. M.; Fahsold, R.; Flodman, P.; Fryer, A.; Halley, D. J J; Jewell, A.; Janssen, L. A J; Kandt, R.; Northrup, H.; Osborne, J.; Pericak-Vance, Margaret A; Povey, S.; Sampson, J.

In: Annals of the New York Academy of Sciences, Vol. 615, 04.09.1991, p. 256-264.

Research output: Contribution to journalArticle

Haines, JL, Amos, J, Attwood, J, Bech-Hansen, NT, Burley, M, Conneally, PM, Connor, JM, Fahsold, R, Flodman, P, Fryer, A, Halley, DJJ, Jewell, A, Janssen, LAJ, Kandt, R, Northrup, H, Osborne, J, Pericak-Vance, MA, Povey, S & Sampson, J 1991, 'Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset', Annals of the New York Academy of Sciences, vol. 615, pp. 256-264.
Haines JL, Amos J, Attwood J, Bech-Hansen NT, Burley M, Conneally PM et al. Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset. Annals of the New York Academy of Sciences. 1991 Sep 4;615:256-264.
Haines, J. L. ; Amos, J. ; Attwood, J. ; Bech-Hansen, N. T. ; Burley, M. ; Conneally, P. M. ; Connor, J. M. ; Fahsold, R. ; Flodman, P. ; Fryer, A. ; Halley, D. J J ; Jewell, A. ; Janssen, L. A J ; Kandt, R. ; Northrup, H. ; Osborne, J. ; Pericak-Vance, Margaret A ; Povey, S. ; Sampson, J. / Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset. In: Annals of the New York Academy of Sciences. 1991 ; Vol. 615. pp. 256-264.
@article{5fac7bb8a35a4623805a4929093fef6c,
title = "Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset",
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 of 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 < 0.001), for test 2 the chi-square (1 df) was 0.13 (p > 0.35), and for test 3 the chi-square (2 df) was 37.61 (p < 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.",
author = "Haines, {J. L.} and J. Amos and J. Attwood and Bech-Hansen, {N. T.} and M. Burley and Conneally, {P. M.} and Connor, {J. M.} and R. Fahsold and P. Flodman and A. Fryer and Halley, {D. J J} and A. Jewell and Janssen, {L. A J} and R. Kandt and H. Northrup and J. Osborne and Pericak-Vance, {Margaret A} and S. Povey and J. Sampson",
year = "1991",
month = "9",
day = "4",
language = "English",
volume = "615",
pages = "256--264",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset

AU - Haines, J. L.

AU - Amos, J.

AU - Attwood, J.

AU - Bech-Hansen, N. T.

AU - Burley, M.

AU - Conneally, P. M.

AU - Connor, J. M.

AU - Fahsold, R.

AU - Flodman, P.

AU - Fryer, A.

AU - Halley, D. J J

AU - Jewell, A.

AU - Janssen, L. A J

AU - Kandt, R.

AU - Northrup, H.

AU - Osborne, J.

AU - Pericak-Vance, Margaret A

AU - Povey, S.

AU - Sampson, J.

PY - 1991/9/4

Y1 - 1991/9/4

N2 - 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 of 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 < 0.001), for test 2 the chi-square (1 df) was 0.13 (p > 0.35), and for test 3 the chi-square (2 df) was 37.61 (p < 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.

AB - 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 of 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 < 0.001), for test 2 the chi-square (1 df) was 0.13 (p > 0.35), and for test 3 the chi-square (2 df) was 37.61 (p < 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.

UR - http://www.scopus.com/inward/record.url?scp=0025835499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025835499&partnerID=8YFLogxK

M3 - Article

C2 - 1674844

AN - SCOPUS:0025835499

VL - 615

SP - 256

EP - 264

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -