Thesis (M. Phil.)--University of Queensland, 2002. / Includes bibliographical references.

This thesis describes the development of: (i) an automatic chromosome analysis system capable of producing to a high degree of accuracy and consistency a correct classification for damaged chromosomes at a low cost and (ii) a parallel computer system to enable more rapid chromosome analysis. Chromosomes can be examined in a cytogenetics laboratory for a variety of purposes including an assessment of the affects of ionisation exposure on the genetic code of the cell. Scoring of chromosome aberrations caused by ionisation of radiation exposure, is possible by detecting dicentric chromosomes. In addition this approach provides a good biological radiation measure (dosimeter). However, currently manual methods are extremely time consuming and expensive with respect to labour costs. For the low radiation doses it is necessary to analyse a large number of chromosomes to identify a small number of damaged ones to score the number of aberrations. Consequently, the main objective of this research programme is to develop a rapid, low cost, and accurate automated chromosome analysis system. This research has concentrated solely on scoring dicentric chromosome since their characteristic shape is relatively easy to recognise in most cases and they most commonly created by exposure to radiation. The methods and theories considered in this thesis concerns chromosome image selection by automatic segment extraction using of the following: grey levels; image extraction by seed aggregation, a two dimensional function, a moment algorithm, for chromosome orientation; chromosome centreline determination; rapid detection of the chromosome centromere of the candidate. The new methods developed by the author and presented herein concern three steps or processes in automatic chromosome analysis. These include (i) a new segmentation scheme (ii) automatic selection the cell threshold grey scale level and (iii) the design a new methods capable of detecting bent chromosome with rapid determination the chromosome centromere. Parallel processing using the processor farm technique has been successfully developed to enable a more rapid chromosome classification system. The techniques described have been carefully tested and evaluated and have clearly demonstrated the potential application of the analysis methods by the author.

Zhong, Yangliu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 50-57). / Abstracts in English and Chinese. / Title Page --- p.i / Thesis Committee --- p.ii / Abstract (English Version) --- p.iv / Abstract (Chinese Version) --- p.V / Acknowledgement --- p.vi / Table of Contents --- p.viii / List of Tables --- p.X / List of Figures --- p.xii / List of Abbreviations and Symbols --- p.xiii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- DNA methylation --- p.1 / Chapter 1.2 --- Repair of m3T --- p.2 / Chapter 1.3 --- Objectives of this work --- p.3 / Chapter 1.4 --- DNA structure --- p.3 / Chapter 1.4.1 --- Nomenclature scheme for DNA --- p.3 / Chapter 1.4.2 --- Base pair scheme --- p.4 / Chapter 1.4.3 --- Sugar conformation --- p.5 / Chapter 1.4.4 --- Backbone conformation --- p.7 / Chapter 2 --- Materials and Methods --- p.9 / Chapter 2.1 --- Sample design --- p.9 / Chapter 2.2 --- Sample preparation --- p.10 / Chapter 2.3 --- NMR analysis --- p.10 / Chapter 2.3.1 --- Resonance assignment --- p.12 / Chapter 2.3.2 --- Determination of sugar conformation --- p.13 / Chapter 2.3.3 --- Determination of backbone conformation --- p.14 / Chapter 2.4 --- UV melting study --- p.15 / Chapter 3 --- Effect of m3T on Double-Helical Structures and Stabilities --- p.17 / Chapter 3.1 --- Resonance assignments --- p.17 / Chapter 3.2 --- Effect of m3T on double-helical DNA structures --- p.19 / Chapter 3.2.1 --- Base pairing mode --- p.19 / Chapter 3.2.2 --- Sugar conformation --- p.21 / Chapter 3.2.3 --- Backbone conformation --- p.22 / Chapter 3.3 --- Effect of m3T on double-helical DNA stabilities --- p.25 / Chapter 3.4 --- Discussion --- p.26 / Chapter 3.4.1 --- Single-strand requirement in FTO repair --- p.26 / Chapter 3.4.2 --- Relationship between m3T pairing structure and stability --- p.27 / Chapter 4 --- Effect of m3T Mispair on Double-Helical DNA Structures and Stabilities --- p.28 / Chapter 4.1 --- Resonance assignments --- p.28 / Chapter 4.2 --- Effect of m3T mispair on double-helical DNA structures --- p.32 / Chapter 4.2.1 --- Pairing mode of T m3T --- p.34 / Chapter 4.2.2 --- Pairing mode of G m3T --- p.35 / Chapter 4.2.3 --- Pairing mode of C.m3T --- p.35 / Chapter 4.3 --- Effect of m3T mispair on double-helical DNA stabilities --- p.36 / Chapter 4.4 --- Discussion --- p.36 / Chapter 4.4.1 --- Predominant mutation --- p.37 / Chapter 4.4.2 --- Relationship between m3T pairing structure and stabilities --- p.37 / Chapter 5 --- Conclusion and Future Work --- p.39 / Chapter Appendix I --- Proton chemical shift values (ppm) of AmT --- p.40 / Chapter Appendix II --- Proton chemical shift values (ppm) of RefAT --- p.41 / Chapter Appendix III --- Proton chemical shift values of NmT samples --- p.42 / Chapter Appendix IV --- "Σ1' and %S of TmT, GmT and CmT" --- p.45 / Chapter Appendix V --- "1H-31P HSQC spectra of (a) TmT, (b) GmT and (c) CmT" --- p.46 / Chapter Appendix VI --- "1H-31P COSY spectra of (a) TmT, (b) GmT and (c) CmT" --- p.47 / Chapter Appendix VII --- "31P chemical shifts, 3JH3'P and %Bi of TmT, GmT and CmT" --- p.48 / Chapter Appendix VIII --- "UV melting curves of RefAT, AmT, TmT, GmT and CmT" --- p.49 / References --- p.50

In order to recover new mutant alleles of the Polycomb group gene Additional sex combs (Asx), mutagenized chromosomes were screened over the putative Asx allele XT129. Thirteen new mutant strains that fail to complement XT129 were recovered. Unexpectedly, the thirteen strains sorted into four complementation groups. Recombination mapping suggests that each complementation group represents a separate locus. The largest group fails to complement a deletion of Asx and maps in the vicinity of 2-72, the published location of Asx. All new mutant strains enhance the phenotype of Polycomb mutant flies and are not allelic to any previously discovered second chromosome Polycomb group genes. Therefore, the new mutants may be considered putative new members of the Polycomb group. This study suggests that Asx belongs to a sub-group of genes displaying intergenic non-complementation. / Science, Faculty of / Zoology, Department of / Graduate

Thesis (Honors)--College of William and Mary, 2008. / Includes bibliographical references (leaf 43). Also available via the World Wide Web.

Thesis (M.S.)--Rochester Institute of Technology, 2007. / Typescript. Includes bibliographical references (p. 44-46).

The standard genetic code (SGC) is the cipher used by nearly all organisms to transcribe information stored in DNA and translate it into its amino acid counterparts. Since the early 1960s, researchers have observed that the SGC is structured so that similar codons encode amino acids with similar physiochemical properties. This structure has been hypothesized to buffer the SGC against transcription or translational error because single nucleotide mutations usually either are silent or impart minimal effect on the containing protein. We herein briefly review different theories for the origin of that structure. We also briefly review different computational experiments designed to quantify buffering capacity for the SGC. We report on computational Monte Carlo simulations that we performed using a computer program that we developed, AGCT. In the simulations, the SGC was ranked against other, hypothetical genetic codes (HGC) for its ability to minimize physiochemical distances between amino acids encoded by codons separated by single nucleotide mutations. We analyzed unappreciated structural aspects and neglected properties in the SGC. We found that error measure type affected SGC ranking. We also found that altering stop codon positions had no effect on SGC ranking, but including stop codons in error calculations improved SGC ranking. We analyzed 49 properties individually and identified conserved properties. Among these, we found that long-range non-bonded energy is more conserved than is polar requirement, which previously was considered to be the most conserved property in the SGC. We also analyzed properties in combinations. We hypothesized that the SGC is organized as a compromise among multiple properties. Finally, we used AGCT to test whether different theories on the origin of the SGC could explain more convincingly the buffering capacity in the SGC. We found that, without accounting for transition/transversion biases, the SGC ranking was modest enough under constraints imposed by the coevolution and four column theories that it could be explained due to constraints associated with either theory (or both theories); however, when transition/transversion biases were included, only the four column theory returned a SGC ranking modest enough that it could be explained due to constraints associated with that theory. / Thesis / Master of Science (MSc) / The standard genetic code (SGC) is the cipher used almost universally to transcribe information stored in DNA and translate it to amino acid counterparts. Since the mid 1960s, researchers have recognized that the SGC is organized so that similar three-nucleotide RNA codons encode amino acids with similar properties; researchers consequently hypothesized that the SGC is structured to minimize effects from transcription or translation errors. This hypothesis has been tested using computer simulation. I briefly review results from those studies, complement them by analyzing unappreciated structural aspects and neglected properties, and test two theories on the origin of the SGC.

Studies have discovered higher frequencies of single nucleotide polymorphisms (SNPs) in different mitochondrial genes are associated with subnormozoospermia. However, the frequencies of SNPs in ND1 and ND2 are not unknown. The present research was aimed to determine the frequencies of SNPs in ND1 and ND2 genes of the mitochondrial genome in fertile and subfertile men and whether changes in codon usage was associated with fertility phenotypes. Total genomic DNA from 157 semen samples was extracted using the proteinase K/SDS digestion procedure, followed by phenol/chloroform purification and ethanol precipitation. ND1 and ND2 genes were amplified respectively from 80 and 92 DNA samples from different fertility groups. Each PCR product was sequenced to identify mutations. Codon change resulting from a nucleotide substitution was determined by comparison with a reference mtDNA sequence obtained from the NCBI database. The frequency of codon usage in the reference mtDNA was determined by the computer program MEGA version 2.1. Eleven synonymous nucleotide substitutions and two non-synonymous substitutions were found in this study. Four SNPs were previously characterized; all SNPs were homoplasmic. None of the SNPs were likely to affect the function of the proteins on the basis of the hydrophobicity plots or secondary structure predictions. Sixty two percent of synonymous mutations were found to change from a high to a low relative codon usage values; 37% of synonymous mutations changed from a low to a high relative usage value. Chi-square (χ²) test (χ²= 0.067 with 1 d.f.) showed that there was no significant difference at the 5% level between these changes. Thus, change in codon usage was not related to semen quality in men. Further, there were no statistically significant differences in the observed frequencies of SNPs of fertile and subfertile men. However, the sample size was small and this study was only focused on a single NZ Caucasian population. Further study including larger and more diverse population samples may provide further insight into the functional importance of codon usage and its relevance to fertility

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Vita. / Bibliography: leaves 211-223. / by Douglas Elliott Koshland. / Ph.D.

DNA is the pharmacological target for most platinum drugs; however, the majority of these drugs show little or no specificity for particular base pairs. Considerable progress has been made in the design of sequence selective compounds, such that an antiparallel association of a polyamide can have high affinity for selected DNA base pairs. Hairpin polyamides have distinct advantages as they achieve affinities and specificities that are comparable to that of DNA-binding proteins. Platinum(II) hairpin polyamides are expected to display antitumour activity and target specific sequences of DNA. Five DNA-sequence-selective hairpin polyamide platinum(II) complexes, containing pyrrole (Py) and imidazole (Im) heterocyclic rings, have been synthesised using a combination of solid and solution phase chemistry. One mononuclear sequence selective complex, β-Ala-PyPyPy-L4-ImImIm-L4-Pt (HLSP-6) [β-Ala is β-alanine, L4 is 4-(Fmoc-amino)butyric acid and Pt is transplatin], and two dinuclear sequence selective complexes, β-Ala-PyPyPy-L4-ImImIm-L6'-Pt-(Pt) (DNHLSP-6) [L6' is 2,6-Fmoc-Lysine-(Fmoc)-OH] and β-Ala-PyPyImImIm-L4'-PyPyPyPyPy-L6'-Pt-(Pt) (DNHLSP-10) (L4' is 2-Boc-4-Fmoc-L-diaminobutyric acid), were synthesised entirely using solid phase chemistry. Two mononuclear sequence selective complexes, Pt-L6-β-Ala-Py-L4-Im (HSP-2) and Pt-L6-β-Ala-PyPyPy-L4-ImImIm (HSP-6), were synthesised using a combination of solid and solution phase chemistry. The synthesis of a trinuclear sequence selective polyamide was also attempted using a combination of solid and solution phase chemistry. The polyamides were synthesised in a series of reaction steps. Each heterocyclic ring and linker was coupled through solid phase chemistry using 2-(1H-benzotriazole-1-y1)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). Once the organic components were assembled, the platinum(II) group/s was/were added using either solid or solution phase chemistry. The polyamide sequence of PyPyPy-L4-ImImIm was designed to target the guanine rich telomere region of DNA. The metal complexes reported in this study will span sequences between 2, 5 or 7 DNA base pairs (depending on their length), which include 5'-(A/T)GGG(A/T)-3' and 5'-(A/T)(A/T)(A/T)GGG(A/T)-3'. All complexes were characterised using 1H and 195Pt NMR, high resolution mass spectrometry and elemental analysis. The binding of HLSP-6 and DNHLSP-6 to guanosine was also monitored by 1H NMR. / Doctor of Philosophy (PhD)