Nonsyndromic cleft lip with or without cleft palate in west Bengal, India: evidence for an autosomal major locus.
Ninety extended families having one or more individuals affected with nonsyndromic cleft lip (CL) with or without cleft palate (CL/P) were ascertained in rural West Bengal, India. These families included 138 affected people, 64% of whom had CL alone and 66% of whom were male. Multiple-affected-member ("multiplex") pedigrees were less common than single-affected-member ("simplex") pedigrees, composing 34% of all extended pedigrees. There was no difference between multiplex and simplex pedigrees in the frequency of affected persons with CL alone, but multiplex pedigrees had a lower frequency of affected males (58%) than did simplex pedigrees (76%; P = .02). Complex segregation analysis using the POINTER computer program rejected both the hypothesis of no familial transmission (P < .0001) and the hypothesis that familiarity could be explained solely by a multifactorial/threshold model (P < .05). The hypothesis of major-locus inheritance alone could not be rejected. Among major-locus models examined, strictly recessive inheritance was rejected (P < .0001), but codominant and dominant models were not. Neither the addition of a multifactorial component nor the addition of a proportion of sporadic cases to the major-locus model improved the fit of the data. In conclusion, the results of complex segregation analysis were consistent with a dominant or codominant major-locus mode of inheritance of CL/P in these families.
Ray
A K
AK
University of Toronto, Alberta, Canada.
Field
L L
LL
Marazita
M L
ML
D000328:Adult; D016009:Chi-Square Distribution; D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003241:Consanguinity; D003433:Crosses, Genetic; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007194:India; D016013:Likelihood Functions; D008297:Male; D008957:Models, Genetic; D011995:Recombination, Genetic; D012744:Sex Ratio