Combined segregation and linkage analysis of nonsyndromic orofacial cleft in two candidate regions

We applied a complex segregation analysis to 46 pedigrees with a total of 1 21 nuclear families and 660 individuals, to verify hypotheses regarding the inheritance of OFC and linkage with markers on chromosomes 6 and 2. The PO INTER program for segregation analysis strongly rejected the hypothesis of no familial transmission of OFC in these families. When the hypothesis of a two-locus model was tested with COMDs, the analysis showed the presence of at least two loci and the model assuming a dominant major gene and a reces sive modifier locus was statistically accepted. Given the fitted two-locus model, we tested for a possible linkage between the major OFC locus and the two markers studied. For D6S259, the estimate of the recombination fractio n was theta = 0.098, corresponding to a LOD score around 2.1. On the contra ry, the data analysis concerning the D2S378 marker showed an estimate of th e recombination fraction not significantly different from the independence hypothesis.