رسالة جامعية
Διερεύνηση γενετικών παθήσεων και συνδρόμων με ανωμαλίες στο χρωμόσωμα Χ ; Investigation of X-chromosome abnormalities
| العنوان: | Διερεύνηση γενετικών παθήσεων και συνδρόμων με ανωμαλίες στο χρωμόσωμα Χ ; Investigation of X-chromosome abnormalities |
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| المؤلفون: | Koumbaris, Georgios, Κουμπαρής, Γεώργιος |
| بيانات النشر: | University of Ioannina Πανεπιστήμιο Ιωαννίνων |
| سنة النشر: | 2011 |
| المجموعة: | National Archive of PhD Theses (National Documentation Centre Greece) |
| مصطلحات موضوعية: | Ισοχρωμοσωμα, Ρετρομεταθετά στοιχεία, Χρωμοσωμικές αναδιατάξεις, Χρωμόσωμα Χ, Ομόλογος ανασυνδυασμός μη αλληλόμορφων αλληλουχιών, Μηχανισμός ένωσης τελικών μη ομολόγων τμημάτων, Isochromosome, i(Xq), NAHR, NHEJ, FoSTeS, MMBIR, Genomic disorders, Ιατρική και Επιστήμες Υγείας, Κλινική Ιατρική, Medical and Health Sciences, Clinical Medicine |
| الوصف: | In order to elucidate the mechanisms of i(Xq) formation, and determine whether architectural elements of the genome cause region-specific instability which predisposes to isochromosome formation, we collected a large cohort of patients bearing abnormal X chromosomes. By analyzing these cases using high resolution methodologies such as high resolution whole genome aCGH, custom targeted aCGH and sequencing, we were able to characterize the cytogenetically monocentric i(Xq) in great detail and derive valuable insights about their breakpoint distribution and potential mechanisms of formation. We were also able to elucidate the mechanisms of cytogenetically dicentric i(Xq) formation and identify specific genomic architectural elements which catalyze, or induce the formation of these rearrangements. We show that not all dicentric i(Xq) are the same in relation to their breakpoint morphology and distribution. In our cohort of 68 patients, we identified 34 i(Xq) cases. Out of these 34 i(Xq), 15 are cytogenetically monocentric having breakpoints in centromeric heterochromatin. Further analysis revealed that the majority of these cases are structurally dicentric and probably form by unequal recombination between inverted centromeric repeats. The remaining 19 i(Xq) of the total 34 i(Xq) were dicentric isochromosomes having breakpoints in euchromatic sequences within a 7-Mb common breakpoint interval in proximal Xp. Targeted ultra-high resolution aCGH and sequencing revealed that 9 of these 19 i(Xq) have breakpoints which coincide precisely with the junctions of large and highly homologous palindromic LCRs, while another four of the 19 i(Xq) have the same breakpoint which coincides with a single highly homologous LINE, L1 palindrome. Based on these findings, we conclude that these 13 i(Xq) arise by NAHR involving LCR palindromes and a single LINE, L1 palindrome. The remaining 6 i(Xq) out of the 19 i(Xq) have breakpoints in regions of no significant homology, and at the breakpoint junctions of three of them inverted ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/10442/hedi/25762Test |
| DOI: | 10.12681/eadd/25762 |
| الإتاحة: | https://doi.org/10.12681/eadd/25762Test http://hdl.handle.net/10442/hedi/25762Test |
| رقم الانضمام: | edsbas.88D3C93B |
| قاعدة البيانات: | BASE |
| DOI: | 10.12681/eadd/25762 |
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