[Possible association due to linkage disequilibrium of TGFA, RARA and BCL3 with nonsyndromic cleft lip with or without cleft palate in the Chilean population].
BACKGROUND
Nonsyndromic cleft lip/palate (NSCLP) is a congenital malformation with the characteristics of a complex genetic trait. Based on experimental evidences as well as on association and linkage studies candidate genes TGFA, RARA and BCL3 have been postulated as being involved in the genetic etiology of this pathology.


OBJECTIVE
To test the possible association due to linkage disequilibrium between microsatellite markers located at less than 1cM from the three candidate genes and nonsyndromic cleft lip/palate using the case-parents trio design.


METHODS
The sample consisted of 58 case-parents trios. Two microsatellite markers, flanking each one of the candidate genes were analyzed by means of the polymerase chain reaction (PCR) with fluorescent labeled microsatellite markers. Electrophoresis of the PCR products was performed on a laser-fluorescent automatic DNA sequencer. Nonparametric ETDT was used to analyze the genotype data.


RESULTS
Significant linkage disequilibrium was detected between D2S443 (TGFA) and NSCLP. Significance was almost reached between D17S800 (RARA) and NSCLP. Alleles 239bp (D2S443) and 172bp (D17S800) showed significant preferential transmission from heterozygous parents to affected offspring. In the case of BCL3 both markers showed no significant results.


CONCLUSIONS
The results of the present study do not show clear evidence that TGFA or RARA could be involved in the genetic etiology of NSCLP. Even though the importance of retinoic acid in the development of the embryo is well documented the results obtained for RARA are difficult to analyze. In relation to the possible role of BCL3 in NSCLP, recent information postulates that other genes located in the same chromosome region could be involved in NSCLP.
Suazo
José
J
Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.
Santos
José Luis
JL
Silva
Viviana
V
Jara
Lilian
L
Palomino
Hernán
H
Blanco
Rafael
R
D000483:Alleles; D000081242:B-Cell Lymphoma 3 Protein; D002677:Chile; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha