Defense Date


Document Type


Degree Name

Doctor of Philosophy


Human Genetics

First Advisor

Judith A. Brown


I have studied 26 children who have a de novo rearrangement of the acrocentric chromosomes in order to understand the formation of these aberrations. The families include '25 probands ascertained for Robertsonian-type translocations, 13 between nonhomologous chromosomes and 12 between homologs, and one rea(21;21)(q22;q22). The parental origins of the de novo rearrangements were determined in 26/26 families using QFQ and NOR variants and/or RFLP analyses. While there was no overall difference in the sex distribution of the parents of origin, there were more maternally derived nonhomologous ("true" Robertsonian) translocations (8 mat: 5 pat) and more paternally derived homologous rearrangements (4 mat: 9 pat). A role of the NOR in de novo formation of acrocentric rearrangements was suggested by a significantly higher incidence of dNOR variants in the parents in whom the rearrangements originated (11/26) as compared to their normal spouses (1/26) and a control population (5/50) (p<0.0001). The dNOR variant was found both in parents in whom de novo Robertsonian.translocations and homologous rearrangements had occurred. Additionally, both the parents in whom rearrangements originated and their spouses had significantly higher NOR scores than the controls. This suggests that higher NOR scores in the parents may have contributed to the survival of their offspring with de novo acrocentric rearrangements since these rearrangements generally resulted in the loss of two NORs. However, compensation in NOR scores or satellite associations was not evident in these probands. RFLP analysis of rearrangements between homologous chromosomes resulting in secondary trisomy in 8 cases suggested that these rearrangements were isochromosomes, derived from one parental chromosome. Four of the homologous rearrangements were dicentric suggesting that these rearrangements may have resulted from U-type exchanges in the NOR or short arm.


Scanned, with permission from the author, from the original print version, which resides in University Archives.


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