Linkage analysis of candidate regions in Swedish nonsyndromic cleft lip with or without cleft palate families

Objective: To analyze linkage of five candidate regions for nonsyndromic cl eft lip with or without palate (CLP) on chromosome 2p13, So, 6p23, and 19q1 3; in addition chromosome 1q32, the locus for van der Woude syndrome, on Sw edish CLP families. Design: Three to five linked microsatellite markers were selected from each candidate region. Polymerase chain reaction (PCR) with fluorescent-labeled microsatellite markers was performed on DNA samples from the participating families. Electrophoresis of the PCR products was performed on a laser-flu orescent DNA sequencer. The genotype data were analyzed with multipoint lin kage analysis. Modes of inheritance tested included two autosomal dominant, an autosomal recessive, and a nonparametric model. Multipoint logarithm of odds (LOD) scores were also calculated by assuming genetic heterogeneity. Participants: Nineteen Swedish multigenerational families with at least two first-degree relatives affected with CLP, Greater than 50% of the families studied show vertical transmission of the clefting phenotype and both inte r- and intrafamilial variability were noted. Results: Cumulative multipoint LOD scares for the whole group of families c alculated under autosomal dominant modes of inheritance were negative in al l regions and less than -2 except chromosome 6p23. LOD scores calculated un der recessive inheritance and the nonparametric model were inconclusive. Th ere was no significant evidence of genetic heterogeneity among the sample g roup. Conclusions: The group of Swedish CLP families did not demonstrate signific ant linkage to any of the five candidate regions examined. This might sugge st a new but yet unknown CLP locus or loci in this family group. However, b ecause linkage could not be excluded in some individual families, they shou ld still be tested with candidate genes from these regions.