Complex segregation analysis of nonsyndromic cleft lip/palate in amerindian/caucasian admixture populations from Colombia

Abstract

ABSTRACT: The present study was undertaken to examine the pattern of inheritance of cleft lip and palate (CLP) in pedigrees ascertained from localities belonging to Cundiboyacense altiplano, Colombia. This population has long been known to be the result of the admixture between Amerindian/Spaniard communities five centuries ago. Ninety-eight extended and multigenerational pedigrees, constituted by 125 nuclear components and 651 records were analyzed. Nine hypothetical models were contrasted using likelihood ratio tests. The hypotheses of no familial transmission, multifactorial component compared against that of the existence of a major gene only, the existence of a recessive major gene, that of non major component in the mixed model and that of the non transmission of major effect (t1=12= t3) were rejected. In contrast, hypotheses postulating a major locus (dominant, codominant) and that of no polygenic component in the mixed model could not be rejected. The major gene model without restrictions in d was the most parsimonious. Thus far, the most parsimonious model is that of a major gene (dominant-codominant) without multifactorial effects. Thus, it must be emphasized that, at least in the Colombian communities, environmental components in predisposing to CLP, as has been pointed out in those hypothesis involving fungicides and some kind of avitaminosis, must be discarded and the genetic mendelian factors must be the focus of research.

RESUMEN: El presente estudio fue realizado para evaluar el patrón hereditario de labio/paladar hendido (LPH) en genealogías analizadas en localidades pertenecientes al altiplano cundiboyacense colombiano. Esta población se originó hace cinco siglos como resultado de la mezcla entre las comunidades Amerindia e Hispánica. Se analizaron 98 genealogías multigeneracionales extendidas, constituidas por 125 componentes nucleares y 651 individuos. Se contrastaron nueve modelos hipotéticos mediante el test de verosimilitud. Las hipótesis de no-transmisión familiar y el componente multifactorial, comparadas contra la hipótesis de existencia de un gen mayor y de un gen mayor recesivo, y la no-existencia del componente mayor en el modelo mixto y no-transmisión de efectos mayores (t1=12=t3), fueron refutadas. En contraste, no pudieron refutarse las hipótesis postulando un locus mayor (dominante, codominante) y un componente no poligénico en el modelo mixto. El modelo de gen mayor (dominante, codominante) sin efectos multifactoriales fue el más parsimonioso. En conclusión, debe enfatizarse que, por lo menos en las comunidades colombianas, deben descartarse las hipótesis que involucren componentes ambientales, tales como fungicidas y algunos tipos de avitaminosis como factores que predisponen al desarrollo de LPH, y enfocar las investigaciones en la determinación de dichos factores mendelianos.