Investigador: Lígia S. Almeida
Instituição: Departamento de Genética – INSA, Porto

Este estudo tem como objetivo a implementação de uma nova estratégia para a sequenciação completa do mtDNA usando as novas tecnologias de sequenciação massiva e definição de um algoritmo de análise.

Abstract

Mitochondrial diseases are thought to be the most common form of metabolic disease occurring in childhood, with an estimated frequency of 1 in 5,000 live births. Because of dual genetic control, mitochondrial disorders can originate from mutations either in mitochondrial DNA (mtDNA) or, most frequently, in nuclear genes that encode mitochondrial proteins. Mitochondrial DNA is highly susceptible to mutation and several mtDNA variants result in a variety of syndromes with neurological, muscular, or metabolic manifestations. Indeed, it has been shown that more than 250 mtDNA point mutations and deletions are linked to human diseases. Lesions in this tiny “genome” account for 15 to 30% of all childhood cases. Whole mtDNA can be routinely resequenced by amplification of 46 fragments followed by Sanger sequencing. In this proposal, we aim to successfully apply a Massive Parallel Sequencing strategy, together with a dedicated data analysis pipeline, in whole mtDNA analysis. A training set of samples will be set to optimize the entire process and a second group of samples will be used to validate and independently evaluate the performance of the analysis pipeline.