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dc.contributor Ph.D. Program in Molecular Biology and Genetics.
dc.contributor.advisor Tolun, Aslı.
dc.contributor.author Çetinkaya, Murat.
dc.date.accessioned 2023-03-16T11:28:07Z
dc.date.available 2023-03-16T11:28:07Z
dc.date.issued 2010.
dc.identifier.other BIO 2010 C48 PhD
dc.identifier.uri http://digitalarchive.boun.edu.tr/handle/123456789/15497
dc.description.abstract Genetic linkage analysis is applied to identify loci that harbor gene or genes associated with a disease. It is possible to map disease loci by observing alleles the segregation of microsatellite or SNP markers with the disease in families, it is possible to map disease loci. Availability of densely spaced microsatellite marker maps and genomewide SNP scans have made such studies feasible. In the framework of this thesis, genomewide linkage data were evaluated with parametric linkage analysis software and haplotype segregation studies for four inherited disorders. Furthermore, candidate loci identified were further investigated by fine-mapping and candidate gene approach. Autosomal Recessive Ataxia (ARA) is a subgroup of hereditary ataxias, and characterized by slowly progressive impaired coordination of gait, hands, eye movements and speech. Nine patients from two consanguineous families were included in the study. We found that Aprataxin gene was mutated in six patients. Three patients were homozygous for a known nonsense mutation, and three patients for a novel missense mutation. For the three remaining patients clinical reevaluation revealed that they were afflicted with another disease, but no responsible locus could be identified. Autosomal recessive Larsen Syndrome (LRS) is characterized by congenital largejoint dislocations and craniofacial abnormalities. Seven consanguineous families were analyzed. In four families disease was mapped to 17q25.3 and homozygous mutations were found in Calcium Activated Nucleotidase 1. Three patients had the same known missense mutation. In one family, a novel missense mutation was identified. No common candidate region could be defined for the remaining three families. Juvenile Parkinsonism (JP) is characterized by classical triad of parkinsonism signs, bradykinesia, rigidity and resting tremor and disease onset before the age of 40 years. A missense variant in AK3L1 was identified in homozygous state in all patients but also in a healthy individual in the family. This variant was not detected in any of the 130 control individuals. We propose that an undetermined second locus either contributes to the disease manifestation in patients or protects the homozygous healthy individual. Lastly, autosomal recessive Congenital Cerebellar Hypoplasia (CCLH), characterized by nonprogressive congenital cerebellar ataxia with mental retardation, delayed motor development, disturbed coordination, hypotonia and cerebellar Hypoplasia was studied in two families. In one of the families we mapped the disease to 6q16.1-22.1. No candidate gene could be defined in the region. In the other family, several candidate loci at other chromosomal regions were found.
dc.format.extent 30cm.
dc.publisher Thesis (Ph.D.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2010.
dc.relation Includes appendices.
dc.relation Includes appendices.
dc.subject.lcsh Genetic disorders.
dc.subject.lcsh Gene amplification.
dc.subject.lcsh Polyacrylamide gel electrophoresis.
dc.subject.lcsh Chromosome polymorphism.
dc.title Gene hunt in four inherited diseases
dc.format.pages xxiii, 121 leaves;


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