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Uniparental disomy as a cause for congenital malformations and or developmental delay in inherited apparently balanced chromosomal rearrangements Lopez-Rangel, Elena


Chromosomal translocations are said to be balanced if there is no apparent gain or loss of genetic material. Apparently balanced chromosomal rearrangements are usually associated with a normal phenotype [Therman 1986, Daniel 1988]. However the frequency of mental retardation and congenital anomalies appears to be increased among individuals who carry a de novo or an inherited apparently balanced chromosomal rearrangement [Funderburk et. al. 1977, Aymeet. al. 1979, Fryns et. al. 1986, Howard-Peebles and Friedman1986]. Uniparental disomy occurs when both chromosomes in a pair are inherited from one parent instead of one of the chromosomes being inherited from each parent [Searle et. al. 1985, Cattanach et. al.1985, Lyon et. al. 1985]. Uniparental disomy has recently been established as a cause for congenital anomalies and mental retardation in humans [Spence et. al. 1988, Voss et. al. 1989, Nicholls et. al. 1989, Henry et. al. 1991, Knoll et. al. 1989, Wanget. al. 1991, Temple et. al. 1991, Pentao 1992]. In mice, uniparental disomy for any chromosome may be produced by mating animals that carry certain chromosomal rearrangements which alter normal meiotic segregation [Cattanach 1985, Cattanach 1986, Cattanach 1988, Cattanach 1989). We have investigated the possibility that uniparental disomy may cause mental retardation and malformations in carriers of an inherited apparently balanced chromosomal translocation. We studied 7 families in which one or more childen with congenital anomalies and mental retardation have inherited an apparently balanced translocation from a carrier parent. In order to establish the parental origin of the chromosomes, we collected blood from both parents and the affected child. We determined the parental origin of each of the chromosomes involved in the translocations using DNA probes that detect highly polymorphic loci which have been previously mapped to these chromosomes [Nakamura et al. 1987,Lathrop et al. 1988, Nakamura et al. 1988, Boerwinkle et al. 1989,Batanian 1990, Standen et al. 1990, Weber et al. 1991, Zoghbi et al. 1991, Ranum et al. 1991, Scharf et al. 1992, Litt et al. 1992].We were able to rule out uniparental disomy for each of the chromosomes involved in the translocation in every patient except one who had inherited an apparently balanced translocation from a carrier parent and who presented with malformations and/or developmental delay. In one patient uniparental disomy was ruled out for one of the chromosomes in the translocation but the markers was uninformative for the other chromosome. We conclude that uniparental disomy is not a common occurence in carriers of inherited apparently balanced reciprocal translocations who present with congenital anomalies and/or developmental delay.

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