• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.41.2019.tde-16042019-140551
Document
Author
Full name
Alan Besborodco
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Otto, Paulo Alberto (President)
Lemes, Renan Barbosa
Naslavsky, Michel Satya
Title in Portuguese
Genética de ceratocone: Estudo genético e molecular de uma família brasileira
Keywords in Portuguese
Brasileiros
Ceratocone
Córnea
Estudo de ligação
Genética médica
Marcadores Molecular
NGS - Senquenciamento de Nova Geração
Abstract in Portuguese
O ceratocone é uma disfunção da córnea, que geralmente manifesta-se por meio de um astigmatismo irregular e de um alto grau de miopia. O estágio avançado da doença é a principal causa de indicação da cirurgia de transplante de córnea. Certamente, trata-se de uma condição complexa, com etiologia multifatorial: fatores genéticos e ambientais estão associados para a expressão fenotípica. A maioria dos casos vistos na prática clínica são não sindrômicos (cursam sem comorbidades) e isolados, mas há uma proporção considerável de casos familiares. Foi feito um levantamento bibliográfico das principais variantes associadas ou relacionadas à doença para auxiliar na investigação. O presente projeto teve por objetivo identificar uma possível variante causal, por meio de estudo de ligação de amplitude genômica (GWLS), de uma família brasileira com 15 afetados por ceratocone, após a extração de DNA e genotipagem das amostras por microarranjo de SNP. Também foi realizado o sequenciamento de exoma do probando, visando filtrar as variantes patogênicas candidatas a explicar a doença. Foram encontradas 123 variantes suspeitas no exoma do paciente avaliado por NGS. Adicionalmente, identificou-se 3 regiões com LOD Score >1 (1p35.2-p34.3; 2q32.3-q33.2; 3q23; 5q11.2-q13.2) e uma com LOD Score>2 (19p13.11-q12). A combinação das duas metodologias permitiu a identificação de três variantes, sendo uma delas provavelmente implicada na etiologia, ainda por validar. Duas outras variantes foram excluídas
Title in English
Genetics of keratoconus: Genetical and molecular study of a Brazilian family
Keywords in English
. Molecular biology
Brazilian
Cornea ectasy
Keratoconus
Linkage study
Medical Genetics
NGS
Abstract in English
Keratoconus is a dysfunction of the cornea, which usually manifests itself through irregular astigmatism and a high degree of myopia. The advanced stage of the disease is the leading cause of indication for corneal transplant surgery. Certainly, it is a complex condition with a multifactorial etiology: genetic and environmental factors acts together to the phenotypic expression. Most of the cases seen in clinical practice are non- syndromic (with no comorbidities) and isolated, but there is a considerable proportion of familial cases. A bibliographic survey of the main variants associated or related to the disease was made to suport the investigation. The present project aimed to identify a possible causal variant by genomic amplitude binding study (GWLS) of a Brazilian family with 15 affected by keratoconus, after DNA extraction and genotyping of the samples by SNP microarray. It was also performed one exome sequencing, aiming to filter out the pathogenic candidate variants from the proband to explain the disease. 123 suspected variants were found in the patient's exams evaluated by NGS. In addition, 3 regions with LOD Score> 1 (1p35.2-p34.3; 2q32.3-q33.2; 3q23; 5q11.2- q13.2) and one with LOD Score> 2 (19p13.11 -q12). The combination of the two methodologies allowed the identification of three variants, one of them probably implicated in the etiology, yet to be validated. Two other variants were excluded
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
There are withheld file due to requirements (data publishing, patents or rights).
Release Date
2024-10-29
Publishing Date
2019-06-05
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2022. All rights reserved.