DOI
https://doi.org/10.25772/AM0E-AW75
Defense Date
2010
Document Type
Thesis
Degree Name
Master of Science
Department
Human Genetics
First Advisor
Colleen Jackson-Cook
Abstract
While age-related sex chromosomal aneuploidy is a well-characterized phenomenon, the relationship between autosomal loss and age remains unclear. The emergence of the specific and highly sensitive fluorescence in situ hybridization (FISH) technology has enabled investigators to study interphase cells, thereby overcoming problems inherent with the study of metaphase spreads for acquired aneuploidy assessment. Despite all the advantages of this technique, there are some limitations that could be misleading when scoring interphase autosomal aneuploidy. In this study we show that sex chromosomal hypoploidy is correlated with age. By using a twin study design, we evaluated Y chromosome hypoploidy frequencies and found that loss of the Y chromosome is likely to be a multifactorial phenotype, being influenced by both genetic and environmental factors. An analysis of acquired aneuploidy frequencies for 13 autosomes in men showed that only one autosome, chromosome 3, had an age-related increase in acquired aberrations levels. Using a multi-probe study design, we determined that an apparent loss of fluorescent signal(s) could result from the coincident positioning (overlaying) of the repeat sequences targeted by the probes (due to either somatic homolog pairing or aggregation of the heterochromatic regions). Therefore, caution should be taken when performing autosomal FISH analysis to avoid overestimation of autosomal aneuploidy in uncultured leukocytes.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
December 2010