ABSTRACT
Background: In the search of the major genes responsible for the genetic etiology of Nonsyndromic Cleft Lip and Palate (NSCLP), an association study between this malformation and four molecular markers, F13A1 and EDN1 (6p), D17S579 (17q) and BCL3 (19q), was done. Aim: To determine, in a Chilean population, the presence of NSCLP susceptibility regions, as proposed for Caucasian populations in the 6p, 17q and 19q chromosomal regions. Material and Methods: A sample of unrelated NSCLP patients, that belonged to Simplex (Sx) and Multiplex (Mx) families, was analyzed. Blood donors were used as a control group (Co). The DNA of the four markers was amplified by means of PCR, their products analyzed by PAGE denaturants and visualized by silver staining. Statistical analysis was performed using c2 log ratio. Results: Allele frequency distribution of D17S579 was significantly different in all patients with NSCLP and their subgroups, when compared to control subjects. Significant differences in EDN1 frecuency were observed between the total groups of NSCLP patients and those pertaining to the Mx subgroup, when compared to controls. Differences in F13A1 distribution were only observed between NSCLP-Mx patients and controls. There was a slight difference in BCL3 distribution, between the total sample of NSCLP patients and controls. Conclusions: Our results support the hypothesis of the existence of cleft susceptibility regions in 6p and 17q. The small significance of BCL3, suggests that ethnicity can influence the interactions between involved genes
Subject(s)
Humans , Male , Female , Phenotype , Cleft Lip , Cleft Palate , Microsatellite Repeats/genetics , Alleles , Gene FrequencyABSTRACT
Background: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial defect. Association studies have suggested that a cleftinglocus is located on chromosome 4q at or near two microsatellite markers D4S175 and D4S192. Aim: To test the hypothesis on the possible presence of a clefting locus on chromosome 4q. Material and methods: We carried out an association study on a sample of unrelated NSCLP patients, of their unaffected relatives and in controls. Both probands and relatives were further analyzed depending if they originated from simplex or multiplex families. DNA was analyzed with two PCR markers close to the putative NSCLP locus, dinucleotide repeats D4S175 and D4S192. PCR products were resolved by PAGE and visualized by silver staining. Statistical analysis was performed by means of c2 log ratio. Results: Significant differences between NSCLP and controls were observed when comparing the allele frequency distribution of D4S192 both in the total sample as well as in NSCLP-multiplex and simplex cases. No significant differences for D4S175 were observed in any of the comparisons. Unaffected relatives showed significant differences with controls both for D4S175 and D4S192. Conclusions: Our results support the hypothesis that a NSCLP locus maps on chromosome 4q close to the microsatellite marker D4S192. No differences were observed between NSCLP multiplex and simplex cases versus controls, implying that they do not represent different etiologic entities. The results of the present and previous studies in the same group of patients support the hypothesis that several major interacting genes participate in the etiology of NSCLP