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. 1991 Sep;49(3):674–681.

Complex segregation analysis of nonsyndromic cleft lip and palate.

J T Hecht 1, P Yang 1, V V Michels 1, K H Buetow 1
PMCID: PMC1683132  PMID: 1882845

Abstract

This study was undertaken to examine the inheritance pattern of nonsyndromic cleft lip with or without cleft palate (CL/P). Complex segregation analysis using the unified model as in POINTER and the regressive model as in REGD programs were applied to analyze a midwestern U.S. Caucasian population of 79 families ascertained through a proband with CL/F. In REGD, the dominant or codominant Mendelian major locus models of inheritance were the most parsimonious fit. In POINTER, besides the Mendelian major locus model, the multifactorial threshold (MF/T) model and the mixed model were also consistent with the observed data. However, the high heritability parameter of .93 (SD .063) in the MF/T model suggests that any random exogenous factors are unlikely to be the underlying mechanisms, and the mixed model indicates that this high heritability is accounted for by a major dominant locus component. These findings indicate that the best explanation for the etiology of CL/P in this study population is a putative major locus associated with markedly decreased penetrance. Molecular studies may provide further insight into the genetic mechanism underlying CL/P.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carter C. O. Genetics of common single malformations. Br Med Bull. 1976 Jan;32(1):21–26. doi: 10.1093/oxfordjournals.bmb.a071318. [DOI] [PubMed] [Google Scholar]
  2. Chung C. S., Beechert A. M., Lew R. E. Test of genetic heterogeneity of cleft lip with or without cleft palate as related to race and severity. Genet Epidemiol. 1989;6(5):625–631. doi: 10.1002/gepi.1370060507. [DOI] [PubMed] [Google Scholar]
  3. Chung C. S., Bixler D., Watanabe T., Koguchi H., Fogh-Andersen P. Segregation analysis of cleft lip with or without cleft palate: a comparison of Danish and Japanese data. Am J Hum Genet. 1986 Nov;39(5):603–611. [PMC free article] [PubMed] [Google Scholar]
  4. De Paepe A. Dominantly inherited cleft lip and palate. J Med Genet. 1989 Dec;26(12):794–794. doi: 10.1136/jmg.26.12.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Demenais F. M., Bonney G. E. Equivalence of the mixed and regressive models for genetic analysis. I. Continuous traits. Genet Epidemiol. 1989;6(5):597–617. doi: 10.1002/gepi.1370060505. [DOI] [PubMed] [Google Scholar]
  6. Demenais F., Le Merrer M., Briard M. L., Elston R. C. Neural tube defects in France: segregation analysis. Am J Med Genet. 1982 Mar;11(3):287–298. doi: 10.1002/ajmg.1320110305. [DOI] [PubMed] [Google Scholar]
  7. Elston R. C., Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. doi: 10.1159/000152448. [DOI] [PubMed] [Google Scholar]
  8. Fraser F. C. The genetics of cleft lip and cleft palate. Am J Hum Genet. 1970 May;22(3):336–352. [PMC free article] [PubMed] [Google Scholar]
  9. Hecht J. T., Annegers J. F., Kurland L. T. Epilepsy and clefting disorders: lack of evidence of a familial association. Am J Med Genet. 1989 Jun;33(2):244–247. doi: 10.1002/ajmg.1320330221. [DOI] [PubMed] [Google Scholar]
  10. Hecht J. T. Dominantly inherited cleft lip and palate. J Med Genet. 1990 Sep;27(9):597–597. doi: 10.1136/jmg.27.9.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kidd K. K., Spence M. A. Genetic analyses of pyloric stenosis suggesting a specific maternal effect. J Med Genet. 1976 Aug;13(4):290–294. doi: 10.1136/jmg.13.4.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lalouel J. M., Morton N. E. Complex segregation analysis with pointers. Hum Hered. 1981;31(5):312–321. doi: 10.1159/000153231. [DOI] [PubMed] [Google Scholar]
  13. Lalouel J. M., Rao D. C., Morton N. E., Elston R. C. A unified model for complex segregation analysis. Am J Hum Genet. 1983 Sep;35(5):816–826. [PMC free article] [PubMed] [Google Scholar]
  14. Marazita M. L., Spence M. A., Melnick M. Genetic analysis of cleft lip with or without cleft palate in Danish kindreds. Am J Med Genet. 1984 Sep;19(1):9–18. doi: 10.1002/ajmg.1320190104. [DOI] [PubMed] [Google Scholar]
  15. Melnick M., Bixler D., Fogh-Andersen P., Conneally P. M. Cleft lip+/-cleft palate: an overview of the literature and an analysis of Danish cases born between 1941 and 1968. Am J Med Genet. 1980;6(1):83–97. doi: 10.1002/ajmg.1320060108. [DOI] [PubMed] [Google Scholar]
  16. Morton N. E., MacLean C. J. Analysis of family resemblance. 3. Complex segregation of quantitative traits. Am J Hum Genet. 1974 Jul;26(4):489–503. [PMC free article] [PubMed] [Google Scholar]
  17. Reich T., James J. W., Morris C. A. The use of multiple thresholds in determining the mode of transmission of semi-continuous traits. Ann Hum Genet. 1972 Nov;36(2):163–184. doi: 10.1111/j.1469-1809.1972.tb00767.x. [DOI] [PubMed] [Google Scholar]
  18. Temple K., Calvert M., Plint D., Thompson E., Pembrey M. Dominantly inherited cleft lip and palate in two families. J Med Genet. 1989 Jun;26(6):386–389. doi: 10.1136/jmg.26.6.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wang J. H., Palmer R. M., Chung C. S. The role of major gene in clubfoot. Am J Hum Genet. 1988 May;42(5):772–776. [PMC free article] [PubMed] [Google Scholar]

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