The research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study addresses: (i) Cytogenetic framework of syntenic correlation and, (ii) applying information-theoretics to determine entropy-dictated synteny across an exhaustive set of orthologs of the test pairs of species. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

A doença de Tay-Sachs (DTS) é uma doença neurodegenerativa, de herança autossômica recessiva, que se manifesta a partir do sexto mês de vida. Crianças afetadas desenvolvem degeneração física e mental intensa, levando à morte até os 5 anos de idade. Não há atualmente cura ou tratamento disponível. Na população judaica, 1 em cada 31 indivíduos é portador da DTS, e a incidência da doença (aproximadamente 1 em cada 4.000 nascimentos) é cerca de 100 vezes maior nesta do que em outras populações. O advento do diagnóstico pré-natal para a DTS e o concomitante desenvolvimento de programas de detecção e orientação de heterozigotos da DTS em populações de judeus Ashkenazitas, iniciados em massa desde 1970, levaram a uma diminuição de 90% da incidência da doença nesta população. Estes programas são realizados em Israel, EUA e no Canadá, na população francocanadense. Três mutações no gene HEXA, codificador da sub-unidade ? da enzima hexosaminidase A, são responsáveis por 98% dos casos da DTS na população judaica Ashkenazita. Esse fato possibilita a utilização de um teste de DNA para a identificação de portadores da DTS nesta população. Segundo o censo do IBGE de 1991, a população judaica no Brasil é de 86.416 indivíduos. Este trabalho visou analisar a necessidade e a aceitação de um programa de detecção e orientação de portadores da DTS nesta população. Em particular, procurou-se (1) estabelecer a freqüência das 3 principais mutações causadoras da DTS na população judaica brasileira; (2) avaliar a reação de indivíduos desta população à proposta de um programa de triagem de portadores da DTS, com o objetivo de orientação para casais em risco de terem crianças afetadas. Este estudo foi realizado em escolas judaicas de ensino médio, em São Paulo e no Rio de Janeiro, seguindo o modelo canadense. Dentre 581 alunos (>=16 anos) que assistiram palestras informativas, 404 participaram da pesquisa, indicando uma taxa de participação de 70%. De acordo com os dados dos formulários de consentimento, aproximadamente 65% dos cromossomos analisados eram de origem judaica Ashkenazita. A análise das 3 mutações comuns no gene HEXA nestes 404 indivíduos detectou 8 portadores da DTS (7 da mutação InsTATC1278 e 1 de IVS12+1). Assim, a freqüência de portadores na amostra foi de 1 em cada 51 indivíduos. Considerando somente os cromossomos de origem judaica Ashkenazita, nossos dados indicam que a freqüência de portadores da DTS na amostra é de 1 em cada 33 indivíduos. As freqüências encontradas são equivalentes àquelas descritas em outras populações judaicas (P>0,05). Baseando-se nestes dados, concluí-se que justifica-se a implementação de um programa de identificação e orientação de portadores da DTS na população judaica brasileira. A contemplação dos diversos aspectos éticos envolvidos são parte essencial deste programa. / Tay-Sachs disease (TSD) is an autossomal recessive disease of lysossome storage characterized by progressive nervous degeneration. Children affected by TSD manifest first symptoms around 6 months and die before 5 years of age. TSD is caused by mutations in the HEXA gene, coding for the ? subunit of the hexosaminidase A enzyme. In the absence of the enzyme, its substrate, GM2 ganglioside, accumulates in the neurons of the central nervous cortex. Late onset TSD (chronic form) is a rare variant phenotype with appearance of first symptoms during the second or third decade of life. In the Ashkenazi jewish population, 1 in every 31 individuals is a TSD carrier. The disease incidence (1 in every 4.000 newborns) is 100 times higher in this population. The advent of pre-natal diagnosis for TSD and the development of preventive screening programs massively adopted by Ashkenazi jewish populations led to a 90% decrease in the disease incidence in this group. Three mutations in the HEXA gene are responsible for 98% of the disease incidence in Ashkenazi jews. This lead to the establishment of a DNA test for detection of TSD carriers in this population. The brazilian Ashkenazi jewish populations is around 100.000 individuals. This work aimed to establish the need and the acceptance of a screening program for this population. Specifically, it established the frequency of the 3 most common TSD mutations in a sample of the brazilian jewish population and evaluated the reaction of the community to the offer of a preventive program. This work was undertaken in jewish senior high-school students, in São Paulo and Rio de Janeiro, following the canadian preventive model. From 581 students (>=16 years old) that attended educational sessions, 404 volunteered to the test, indicating a 70% participation rate. According to the data of the consent form, approximately 65% of the chromosomes were associated to Ashkenazi jewish ancestry. The molecular analysis of the 3 most common mutations in the HEXA gene from the 404 participants detected 8 carriers (7 of InsTATC1278 and 1 of IVS12+1), thus indicating a carrier frequency of 1/51. In the Ashkenazi fraction, the estimated carrier frequency is 1 in 33 individuals. Both frequencies are similar to those described for other jewish communities (P>0,05). Based in this findings, it was concluded that the implementation of a screening program for TSD in the brazilian jewish population is feasible. The ethical aspects involved are an essential part of such a program.

For linkage region on chromosome 5, further fine mapping was performed on a total of three pedigrees. Linkage analysis revealed a maximum two point LOD score of 4.81 at marker D5S2505. Haplotype analysis narrowed the linkage region to 5p15.33-p15.2. Resequencing of five candidate genes, IRX2, IRX1, POLS, CCT5 and CTNND2 within the linkage region did not reveal any myopia mutation. They were therefore excluded as the myopia causative gene. Genotyping of 41 SNPs within this region in a Chinese cohort of 94 high myopia cases and 94 control subjects showed that the allele and genotypes distributions of rs370010 was significantly different between cases and controls (genotype P= 0.01176, allele P=0.00271 and trend P=0.00375). This SNP is located within a hypothetical gene LOC442129. After multiple testing corrections, none of the SNP remained significantly associated with high myopia. This is a novel myopia locus. Further work to identify the myopia gene in this region would involve candidate gene resequencing, family linkage analysis and gene-based SNPs association analysis. / High myopia is defined as refractive error below or equal to -6 dioptres (D). The prevalence of high myopia varies among different populations. The most common pathological structural abnormality in high myopia is the excessive lengthening of the posterior segment of the ocular globe. Apart from causing impaired vision, it may lead to severe ocular complications. The precise mechanistic role of genes and environmental factors in the development of high myopia is still uncertain. Studies of twins and families suggested that heredity is a major contributing factor. While no myopia gene has yet to be identified, 14 putative loci have been found on many chromosomes. In this study, we have utilized different approaches to map the myopia locus in the Chinese population. / In our family-based genome-wide scan program, the whole genome of Chinese high myopia pedigrees was screened by using microsatellite markers. Two point LOD scores > 1 were observed on chromosomes 12 and 5. Regions were further analyzed by fine mapping. For linkage region on chromosome 12, a maximum two point LOD score of 2.71 was obtained at marker D12S88 and suggested linkage region was narrowed at 12q21.31-q22 by haplotype analysis. Lumican located in this region was screened and no segregation of polymorphism was observed within the pedigree. The suggested locus in this study overlapped with the MYP3 but with a smaller interval than the one reported. Lumican was excluded to be the myopia gene in this locus. / In the candidate-gene program, the paired box gene 6 (PAX6) on 11p13, was first studied. Two dinucleotide repeats (AC)m and (AG)n in the promoter region were found to be highly polymorphic. Association was observed between these two repeats with high myopia in which patients had high repeat number in both (AC) m and (AG)n (p-value=0.0001317 and p-value=0.001). Our results indicated that the Chinese population does not show association between high myopia and polymorphisms in PAX6 coding region but the AC and AG dinucleotide repeats in the promoter region was significantly associated with high myopia. / Lam, Ching Yan. / "August 2007." / Source: Dissertation Abstracts International, Volume: 69-07, Section: B, page: 4103. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Errata pasted onto back page. Bibliography: leaves 193-228.

Errata pasted onto back page. / Bibliography: leaves 193-228. / xv, 228 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2001

This thesis seeks to address the critical bottlenecks of current technologies that have slowed the neuroscience research in C. elegans. The objective of this research is to enhance the currently developed systems through the design and construction of simple microdevices and quantitative analytical tools for high-throughput phenotyping C. elegans to investigate functions of nervous systems. First, we developed and used the integrated system combining user-friendly single-layer microfluidics and quantitative analytical tools to study the genetic regulation of target gene expression. We found several putative mutants based on large-scale screens, which would have previously been too labor-intensive to attempt. Second, we developed a simple mathematical model that describes the regulation of a target gene expression. Using the model developed, we simulated phenotypical space of hypothetical mutants to suggest plausible genetic pathways some isolated mutants may affect. Lastly, we developed a high-density multichannel device for rapid trapping, parallel selective stimulating, long-term culturing, and (often repeatedly). We used this integrated system to study the neurodegenerative process based on selective ablation of multiple animals using an optogenetic tool, which would have been taken at least 1 order of magnitude longer. Taken together, we expect that these developments will greatly facilitate a broad range of fundamental, and application studies including aging, neurodegeneration, circuit and behavior.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Oct. 13, 2008). Includes bibliographical references (p. 174-183).

Thesis (M.S.)--Brandeis University, 2009. / Title from PDF title page (viewed on May 29, 2009). Includes bibliographical references.

Thesis (M.S.)--Brandeis University, 2009. / Title from PDF title page (viewed on May 29, 2009). Includes bibliographical references.