THE EFFECTS OF AGE AND HETEROCHROMATIN ON FREQUENCIES OF ACQUIRED CHROMOSOMAL ANEUPLOIDY IN UNCULTURED HUMAN LEUKOCYTES

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Human Genetics

Year dc:date.available

2010

Author dc:creator

• Aboalela, Noran

Contributors dc:contributor

• Colleen Jackson-Cook

• Aging
• Cytogenetic
• Aneuploidy
• Acquired
• Age
• Hypoploidy
• Chromosome
• Medical Genetics
• Medical Sciences
• Medicine and Health Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/167

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1166