Next generation sequencing in research and diagnostics of ocular birth defects

Molecular Genetics and Metabolism
Gordana RacaLisa A Schimmenti

Abstract

Sequence capture enrichment (SCE) strategies and massively parallel next generation sequencing (NGS) are expected to increase the rate of gene discovery for genetically heterogeneous hereditary diseases, but at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. Our study assessed whether array based target enrichment followed by re-sequencing on the Roche Genome Sequencer FLX (GS FLX) system could be used for novel mutation identification in more than 1000 exons representing 100 candidate genes for ocular birth defects, and as a control, whether these methods could detect two known mutations in the PAX2 gene. We assayed two samples with heterozygous sequence changes in PAX2 that were previously identified by conventional Sanger sequencing. These changes were a c.527G>C (S176T) substitution and a single basepair deletion c.77delG. The nucleotide substitution c.527G>C was easily identified by NGS. A deletion of one base in a long polyG stretch (c.77delG) was not registered initially by the GS Reference Mapper, but was detected in repeated analysis using two different software packages. Different approaches were evaluated for distinguishing f...Continue Reading

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Related Concepts

Repetitive Region
Exons
Genome
Enzymes, antithrombotic
Pathogenic Organism
Vision
Candidate Disease Gene
Menopause
Gene Deletion Abnormality
Eye Development

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