Semester

Fall

Date of Graduation

2009

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Biochemistry

Committee Chair

Sharon Wenger.

Abstract

Study One. An estimated five percent of individuals with unexplained mental retardation (MR) have chromosomally unbalanced subtelomere regions. Around half of these individuals inherited the imbalance from a parent with a balanced rearrangement. The frequency of carriers for cryptic balanced translocations is unknown. To determine this frequency, blood samples received from 565 out of 978 phenotypically normal, unrelated individuals were examined using fluorescent in situ hybridization (FISH) probes to analyze all subtelomere regions. No balanced subtelomeric rearrangements were identified. The frequency of balanced cryptic translocations in the general population was estimated to be 1/8,000 from the literature. However, three females out of 379 (0.8%) in this study were determined to be mosaic with regard to the X chromosome. This is a higher frequency than the 1 in 1000 (0.1%) reported incidence for sex chromosome aneuploidies. Study Two . From a clinically abnormal population, 256 patients with unexplained MR and normal karyotypes were tested for subtelomere rearrangements using FISH probes. Nine were abnormal (3.5%), in which five were deletions and four were deletion/duplications. Two polymorphisms (0.7%) were observed. Parents for five of the abnormal cases were evaluated and all but one was inherited from a parent with a balanced subtelomeric translocation or the same deletion with a similar abnormal phenotype. Study Three. Most human telomere length studies have focused on the overall length of telomeres within a cell. Very few studies have examined telomere length for individual chromosome arms. The relationship between chromosome arm size and the relative length of the associated telomere was studied in cultured lymphocytes from 17 individuals using quantitative FISH (Q-FISH). A statistically significant positive correlation (p<0.0001) was found between telomere length and the size of the associated chromosome arm.

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