Estudio de asociación por desequilibrio de ligamiento entre los genes TGFA, RARA, y BCL3 y fisura labiopalatina no sindrómica (FLPNS) en la población chilena / 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. Aim: 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. Patients and 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.

La variación genética de MSX1 presenta un dimorfismo sexual en la fisura labiopalatina no sindrómica en la población chilena / Genetic variation of MSX1 has a sexual dimorphism in non syndromic cleft palate in the Chilean population

Background: Recent studies in mice have demonstrated that the Msx-1 homebox gene is implicated in cleft palate. Thus, it has been suggested that its human homologue, MSX1 (HOX-7), located in chromosome 4 could be involved in the etiology of non syndromic cleft lip palate. Aim: To study the linkage between non syndromic cleft palate and variations of MSX1 gene. Patients and methods: Seventy three patients with non syndromic cleft lip palate (34 simplex and 37 multiplex), 127 unaffected relatives of the cases (61 relatives of simplex cases and 66 relatives of multiplex cases) and 77 controls were studied. DNA was extracted from leukocytes and the intragenic microsatellite sequence was amplified by PCR. Results: A polymorphism of four alleles was observed, 1 (175 bp), 2 (173 bp), 3 (171 bp) and 4 (169 bp). Alleles 2 and 4 showed a joint variation in males with multiplex cleft lip palate and in their respective unaffected male relatives, that was significant when compared with male controls. Instead, the joint variation of alleles 1 and 4 of unaffected female relatives had significant differences with female controls. Females with multiplex cleft lip palate differed from female controls only in allele 1. Conclusions: These results support the hypothesis of a genetic heterogeneity in the etiology of non syndromic cleft lip palate

Morfología dentaria en la evaluación de la etnicidad poblacional / Evaluation of Population ethnicity based on dental morphology

Las características morfológica dentarias, como diente en pala y tubérculo de Carabelli, han sido ampliamente utilizadas en estudios antropológicos y genéticos, dada su alta heredabilidad. La utilización de marcadores genéticos sanguíneos ha permitido establecer una gradiente sociogenética para la población de Santiago que se ha correlacionado en forma directa con la susceptibilidad de esas poblaciones a las fisuras labiopalatinas. Se determinaron las frecuencias poblacionales de marcadores genéticos morfológicos dentarios y serológicos en tres poblaciones de distintos sectores de Santiago (privado, público y fisurados). Se compararon las distancias genéticas respecto a las poblaciones originarias. Los resultados demuestran una gradiente sociogenética similar a la encontrada con los marcadores serológicos aunque más próximas a las poblaciones indígenas. Se concluye que estos rasgos pueden ser una herramienta útil para la evaluación del grado de miscegenación de una determinada población

Diferencias celulares y moleculares en la susceptibilidad a la fisura palatina en el ratón / Cellular and molecular differences in the susceptibility to cleft palate on mice

The aim of this study was to identify possible candidate genes for the susceptibility to cleft palate. We studied hyaluronic and glycoprotein levels with morphometric and histochemical techniques, in palatine process of 13 and 14 days old mouse embryos of strains A/Sn and C/57 BL, that are respectively susceptible and resistant to glucocorticoid and non steroid anti-inflammatory drug induced cleft palate. At 13 days, in palatine process of the resistant strain and when these are still vertical, there was a significantly higher amount of extracellular matrix, constituted principally by hyaluronic acid. These differences disappeared at 14 days, when the processes became horizontal. The basal membrane of the medial palatine epithelium of the susceptible strain, showed interruptions due to a lower amount of glycoproteins. It is concluded that the observed differences in the amount and quality of these molecules, are a consequence of genetic differences that could determine the susceptibility to cleft palate

Agentes medioambientales en la susceptibilidad a las fisuras faciales en el norte de Chile / Environmental agents in facial clefts susceptibility in the north of Chile

En dos hospitales de la II Región, el de Calama y el de Chuquicamata, se analizó la incidencia de fisuras labiales con o sin fisura palatina y de fisura palatina sola. Una tasa de fisuras de 1,47 por mil RNV entre los 17.687 nacimientos consecutivos fue determinado en los dos hospitales. Las tasas por hospital variaron considerablemente obteniéndose en Calama una tasa de 1,07 x 1.000 y en Chuquicamata de 2,37 x 1.000 RNV, la más alta encontrada en Chile. El porcentaje de mezcla indígena de las poblaciones hospitalarias, basado en el estudio de las frecuencias de los grupos sanguíneos ABO y Rh(d) indican que ambas poblaciones tienen un alto, pero similar grado de mezcla (47,1 y 49,1 por ciento, respectivamente). Al correlacionar los grados de mezcla indígena con las tasas de fisuras obtenidas en otros estudios, se aprecia que en Calama el valor es menor a lo esperado, lo que podría estar relacionado con el medio ambiente estresante de la zona