Novel Cleft Susceptibility Genes in Chromosome 6q

• Published in: Journal of dental research Vol. 89; no. 9; pp. 927 - 932
• Main Authors: Letra, A., Menezes, R., Fonseca, R.F., Govil, M., McHenry, T., Murphy, M.J., Hennebold, J.D., Granjeiro, J.M., Castilla, E.E., Orioli, I.M., Martin, R., Marazita, M.L., Bjork, B.C., Vieira, A.R.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.09.2010; International Association for Dental Research; SAGE PUBLICATIONS, INC
• Subjects: Animals; Biological and medical sciences; Brazil; Case-Control Studies; Chi-Square Distribution; Chromosomes, Human, Pair 6; Cleft Lip - genetics; Cleft Palate - genetics; Databases, Genetic; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Gene Frequency; Genetic Loci; Genetic Predisposition to Disease; Haplotypes; Humans; Linkage Disequilibrium; Medical sciences; Mice; Monomeric Clathrin Assembly Proteins - genetics; Non tumoral diseases; Otorhinolaryngology. Stomatology; Palate, Hard - embryology; Polymorphism, Single Nucleotide; Research Reports; Serine Endopeptidases - genetics; Serine Proteases - genetics; White People - genetics; Brazil; chromosome 6q; polymorphism; cleft lip/palate; fine mapping; Human; Cartography; Cleft palate; Cleft lip; Stomatology; Family study; Chromosome 6; Genotype; Congenital cleft; Congenital disease; Gene; Malformation; Risk factor; Genetics; Oral cavity disease; Haplotype; Polymorphism
• ISSN: 0022-0345; 1544-0591; 1544-0591
• DOI: 10.1177/0022034510370004

Cleft lip/palate is a defect of craniofacial development. In previous reports, chromosome 6q has been suggested as a candidate region for cleft lip/palate. A multipoint posterior probability of linkage analysis of multiplex families from the Philippines attributed an 88% probability of harboring a cleft-susceptibility gene to a narrower region on bands 6q14.2-14.3. We genotyped 2732 individuals from families and unrelated individuals with and without clefts to investigate the existence of possible cleft-susceptibility genes in this region. We found association of PRSS35 and SNAP91 genes with cleft lip/palate in the case-control cohort and in Caucasian families. Haplotype analyses support the individual associations with PRSS35. We found Prss35 expression in the head and palate of mouse embryos at critical stages for palatogenesis, whereas Snap91 was expressed in the adult brain. We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene.