Molecular Genetics of Non-syndromic Cleft Palate and Van Derwoude Syndrome

(2001) Genetic heterogeneity and exclusion of a modifying locus at 17p11.2-p11.1 in Finnish families with van der Woude syndrome. (2001) Mapping of the second locus for the Van der Woude syndrome to chromosome 1p34. (2003) Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia. (2003) Linkage and linkage disequilibrium searched between non-syndromic cleft palate and four candidate loci. A genomewide scan of non-syndromic cleft palate only in Finnish multiplex families. Submitted. 5 ABBREVIATIONS bp base pair CATCH cardiac-abnormal facies-thymic hypoplasia-cleft palate-hypocalcemia cM centiMorgan CL cleft lip CP cleft palate CPH cleft of the hard palate CPS cleft of the soft palate CPO cleft palate only CPSM submucous cleft palate CL/P cleft lip with or without cleft palate del deletion dup duplication DNA deoxyribonucleic acid IBD identical by descent IBS identical by state IRF6 interferon regulatory factor 6 LD linkage disequilibrium LOD logarithm of odds Mb megabase MZ monozygous NPL non-parametric linkage analysis PCR polymerase chain reaction RS Robin sequence SNP single nucleotide polymorphism TDT transmission disequilibrium test TGFβ3 transforming growth factor beta3 VWS Van der Woude syndrome 6 ABSTRACT Background Cleft palate is one of the most common congenital malformations. The incidence of non-syndromic cleft palate only is ~1/1000 live births in Finland. The etiopathogenesis of clefts has been widely studied but is still poorly understood. It has been estimated that about half of the cases are nonsyndromic. Nonsyndromic cleft palate is considered to be a genetically complex, multifactorial disease. The aim of our research was to study genetic component influencing on non-syndromic CPO and Van der Woude syndrome (VWS), which is one of the most common cleft syndromes. We also wanted to study the role of collagens in Robin sequence (RS), which is a triad of cleft palate, micrognathia and glossoptosis.