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Genetic and other factors that contribute to variability in cytogenetic expression in fragile X males.

Variability in cytogenetic expression of fragile X has been observed by many investigators. One recent study of families of fragile X brothers concluded that frequency of expression was almost completely controlled by genetic factors. We investigated the extent of genetic control over frequency of expression by evaluating fragile X families from 3 different sources using hierarchal analysis of variance model to calculate the intraclass correlation and the index of heritability, h2. Proportion of variance attributable to families was computed from 2 estimation procedures: 1) a least squares method and 2) a maximum likelihood technique. Results were comparable with one another and indicated that, although genetic factors were significant, differences between laboratories contributed a larger proportion of the total estimated variance. These results partly confirmed previous findings but indicated that the degree of genetic control over the proportion of affected cells was lower than recently suggested.