Вариации в броя копия при деца с нарушения в развитието
| dc.contributor.author | Михайлова/Mihaylova, Марта Григорова/Marta Georgieva | |
| dc.date.accessioned | 2017-09-28T10:13:54Z | |
| dc.date.available | 2017-09-28T10:13:54Z | |
| dc.date.issued | 2017-09-28 | |
| dc.description | дисертационен труд за присъждане на образователна и научна степен “ДОКТОР” Област на висше образование: 4.„Природни науки, математика и информатика” Шифър 4.3. Професионално направление: „Биологични науки” Научна специалност: „Генетика”; София, 2017 г.; - 147 с. + Автореферат /CD/ | en_US |
| dc.description.abstract | Цел и задачи ***** 3.1 Цел *** Целта на настоящата десертация е да се характеризират вариациите на броя копия в генома на деца с вродени аномалии и да се определят генетични нарушения, които играят етиологична и патогенетична роля. *** 3.2 Задачи *** 1. Да се определи честотата и типа на геномните нарушения в изследваната група лица чрез сравнителна геномна хибридизация върху микрочипове. 2. Да се характеризират патологичните вариации на броя копия в генома на деца с вродени аномалии и да се определи съдържанието на гени в тях. 3. Да се направи корелация между патологичните находки и клиничния фенотип. 4. Да се определи честотата и типа на новите варианти в броя на копията в генома на деца с вродени аномалии с неясно клинично значение и да се прекатегоризират според разработени критерии. 5. Да се създаде банка от ДНК-и на деца с вродени аномалии за настоящи и бъдещи изследвания ***** Summary *** Copy number variations in children with disturbance of development The high frequency (3-5 %) of congenital anomalies and intellectual disabilities turn them in to a serious problem, responsible for a high percentage (33%) of neonatal mortality. 40% of the genetic causes behind this, remain unclear. In the recent years, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple congenital anomalies and intellectual disability. This high resolutionable method gives us the opportunity to investigate and identify candidate genes, which could explain the genotype-phenotype correlations. In the current study the investigated groupe included 81 patients with congenital malformations, developmental delay and intellectual disability. We applied CytoChip Oligo microarray, (BlueGnome,Illumina), 4x44k, covering the whole genome with a resolution of 70 kb (kilobases). In the selected group of patients with congenital anomalies, 280 CNVs (Copy number variation) have been proven - 41 pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations of the patient - 3.5). In seven patients with established pathogenic variations, our data revealed 9 pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made based on: the frequency in the investigated group, the size of the variation, the content of genes in the region and the type of the variation (deletion or duplication). In our analysis we proved 11 pathogenic variations associated with the phenotype of the patients, 118 benign variations, 46 variations of unknown clinical significance and finaly we described a new group of a - "probably benign CNVs " - 105. It is noteworthy that in the majority ot the cases the etiology of congenital anomalies remains uncleare which requires further investigation to clarify their clinical significance. Future development. The molecular karyotyping is a suitable method for identification of genomic aberrations and has a number of advantages in the diagnosis of congenital abnormalities and intellectual disability. It was concluded that there is an obvious need to apply new genomic technologies with greater resolution, since a significant proportion of the patients were left with unclear diagnosis. This would facilitate the detection and interpretation of the genomic aberrations in order to make an accurate diagnosis and to optimize the therapeutic approaches. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10861/1314 | |
| dc.language.iso | other | en_US |
| dc.subject | Генетика, медицинска - дисертации; Деца - развитие; Аномалии - деца; Вариации, генетични | en_US |
| dc.subject | Genetics, Medical - dissertations; Variation (Genetics); Child Development; Abnormalities - infancy and childhood | en_US |
| dc.title | Вариации в броя копия при деца с нарушения в развитието | en_US |
| dc.type | Thesis | en_US |
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