Resumen Dentro de los defectos congénitos más frecuentes se encuentran las fisuras labio y/o palatinas (FL/P), presentando una prevalencia de alrededor de 1:1.000 nacimientos vivos. El 70% de FL/P son de tipo no sindrómico, lo cual hace referencia a que se encuentran como un defecto aislado sin anomalías adicionales. Poseen una etiología compleja con un componente tanto ambiental como genético. Con el desarrollo de tecnologías de secuenciación del genoma humano se han identificado variantes polimórficas que pueden estar asociadas al fenotipo de FL/P y por tal motivo pueden contribuir a la etiología multifactorial de éstas. En esta revisión se describen las variantes comúnmente asociadas y su papel en la etiología de las FL/P. Los SNPs localizados en los genes IFR6, MSX1, VAX1, PAX9, CHD1, FGF1, GREM1 y WNT3 se han relacionado significativamente con la presencia de FL/P, y las variantes ubicadas en los genes APC, GSK3, DVL2, BMP4, ABCA4, BHMT, NTN1, TBX1, EPHA3, FAM49A, MGMT, MMP3, TIMP2 y NOG aunque se ha reportado su asociación con la presencia de las fisuras orofaciales aún no es clara su relación con dicho fenotipo. Es importante realizar estudios de identificación de variantes genéticas que involucren poblaciones específicas con el fin de poder comprender la etiología de las FL/P no sindrómicas.

Abstract Among the most frequent congenital defects are cleft lip and/or palate (CL/P), with a prevalence of 1:1,000 live births. 70% of CL/P are non-syndromic, which means that they are found as an isolated defect without additional anomalies. They have a complex etiology with both an environmental and genetic component. By the development of human genome sequencing technologies have been identified polymorphic variants that may be associated with the CL/P phenotype and therefore may contribute to the multifactorial etiology of these. This review describes the commonly associated variants and their role in the etiology of CL/P. The SNPs located in the genes IFR6, MSX1, VAX1, PAX9, CHD1, FGF1, GREM1 and WNT3 have been significantly related to the presence of CL/P, and the variants located in the genes APC, GSK3, DVL2, BMP4, ABCA4, BHMT, NTN1, TBX1, EPHA3, FAM49A, MGMT, MMP3, TIMP2 y NOG, although its association with the presence of orofacial fissures has been reported, its relationship with this phenotype is not yet clear. It is important to carry out studies to identify genetic variants that involve specific populations in order to understand the etiology of non-syndromic CL/P.

The hRAD54 gene is a key member of the RAD52 epistasis group involved in repair of double-strand breaks (DSB) by homologous recombination (HR). Thus, alterations of the normal function of these genes could generate genetic instability, shifting the normal process of the cell cycle, leading the cells to develop into cancer. In this work we analyzed exon 18 of the hRAD54 gene, which has been previously reported by our group to carry a silent polymorphism, 2290 C/T (Ala730Ala), associated to meningiomas. We performed a PCR-SSCP method to detect the polymorphism in 239 samples including leukemia and normal control population. The results revealed that the 2290 C/T polymorphism has frequencies of 0.1 for the leukemia and 0.1 for the control group. These frequencies show no statistical differences. Additionally, we dissected the leukemia group in chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) to evaluate the polymorphism. The frequencies found in these subgroups were 0.14 for CML and 0.05 for ALL. We found statistically significant differences between CML patients and the control group (p < 0.05) but we did not find significant differences between ALL and the control group (p > 0.05). These results suggest a possible link between the 2290 C/T polymorphism of the hRAD54 gene and CML.

We analyzed the consequences of aerial spraying with glyphosate added to a surfactant solution in the northern part of Ecuador. A total of 24 exposed and 21 unexposed control individuals were investigated using the comet assay. The results showed a higher degree of DNA damage in the exposed group (comet length = 35.5 µm) compared to the control group (comet length = 25.94 µm). These results suggest that in the formulation used during aerial spraying glyphosate had a genotoxic effect on the exposed individuals.