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Development and App...
Development and Application of Human Chromosome 22 Genomic Microarray : Chromosome 22-Associated Disorders Analyzed by Array-Based Comparative Genomic Hybridization
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- Benetkiewicz, Magdalena, 1977- (författare)
- Uppsala universitet,Institutionen för genetik och patologi
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Dumanski, Jan (preses)
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Dahl, Niklas (preses)
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- Speleman, Frank, Prof.dr. (opponent)
- Center for Medical Genetics Ghent (CMGG), Ghent
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(creator_code:org_t)
- ISBN 9155464394
- Uppsala : Acta Universitatis Upsaliensis, 2006
- Engelska 56 s.
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 99
- Relaterad länk:
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https://uu.diva-port...
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Abstract
Ämnesord
Stäng
- The array-based form of comparative genomic hybridization (array-CGH) is a new methodology that has shown to be of significant importance. This thesis focuses on the development of array-CGH with the aim to define candidate regions/genes on chromosome 22 in a wide spectrum of cancer-related conditions. In paper I, we developed and applied the first comprehensive genomic microarray, representing human chromosome 22, for analysis of DNA copy number. Using this array-based approach, we identified gene copy number alterations, including heterozygous/homozygous deletions, amplifications, IGLV/IGLC locus instability and the breakpoints of imbalanced translocation, in several 22q-associated disorders. In paper II, we applied the same array to perform DNA copy number profiling of a series of ovarian carcinoma. cDNA arrays were also used in this study to correlate gene expression levels with DNA-copy number. In the course of this analysis, we determined a small 3.5 Mb candidate 22q telomeric region and suggested a number of specific candidate genes. Paper III described the comprehensive and high-resolution analysis of chromosome 22 in a large set of various stage breast cancers. Multiple distinct patterns of genetic aberrations were observed. The smallest identified candidate locus was 220 kb in size and mapped to a gene-rich region in the vicinity of telomere of 22q. Intriguing result of this study was the detection of high frequency (26.6%) of intra-tumoral clonal variation in gene copy number profiles, which should be viewed as a high number, considering that we study in detail only a single human chromosome. In paper IV, we profiled a series of 28 Wilms tumor samples using 22q-array in order to assess specific regions affected with DNA dosage-alterations. The distribution of aberrations defined a complex amplifier genotype and delimited two tumor suppressor/oncogene candidate loci. These results open up for several avenues for continued research of these tumor forms. These findings also demonstrate the power of array-CGH in the precise determination of minute DNA copy number alterations and strengthen the notion that further studies, preferentially in the context of the entire human genome, are needed.
Ämnesord
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Nyckelord
- Molecular genetics
- DNA copy number changes
- chromosome 22
- genomic microarray
- array-CGH
- schwannoma
- neurofibromatosis type 2
- ovarian carcinoma
- breast cancer
- Wilms tumor
- Genetik
- Genetics
- Genetik
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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