Identification of novel genes involved in brain abnormality syndromes using next generation sequencing
<p>Since the 1980s there has been a steady increase in the number of genes identified which play a role in human disease. The Human Genome Project and arrival of Next Generation Sequencing (NGS) have helped accelerate the rate of discovery such that the recent update of the Human Gene Mutation...
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| Format: | Thesis |
| Language: | English |
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2014
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| Summary: | <p>Since the 1980s there has been a steady increase in the number of genes identified which play a role in human disease. The Human Genome Project and arrival of Next Generation Sequencing (NGS) have helped accelerate the rate of discovery such that the recent update of the Human Gene Mutation Database (HGMD) lists over 140 thousand genetic variants linked to human disease. However, causative genes have only been identified in half of the 7000 rare monogenic disorders. It is predicted that within 10 years the majority of disease-causing genes will be identified. In many ways the era of next-generation sequencing has become the “gold rush” of disease gene discovery.</p> <p>The aim of this thesis was to demonstrate the validity of an NGS approach to identify novel disease genes associated with brain abnormality phenotypes. In a cohort of 23 families with a range of brain abnormality phenotypes, novel disease genes were found in 2 families and there was an overall clinical diagnosis rate of 38%. The results from this thesis have already expanded the spectrum of brain abnormality mechanisms to include the gene PGAP3. The strategy outlined will become part of the clinical framework for the diagnosis and identification of brain abnormality syndromes with NGS.</p> |
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