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Chunk #30 — Future insights into AD genetics: from GWASs to next-generation sequencing (NGS)

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The genetics of Alzheimer's disease.
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Since AD is a genetically heterogeneous disorder, GWASs have been performed for identification of novel disease risk-factor loci. Several genes and mutations have been tested to find association with disease-related phenotypes, such as changes in biomarker levels and/or neuropathology.189 Sanger sequencing is a widely used technology, but it has limitations in terms of cost, speed, and efficacy. High-throughput or NGS technologies are recent hot topics in genomic research of animals and humans. NGS technologies included sequencing by synthesis, ligation, or hybridization; single-molecule sequencing; nanopore sequencing; and colony sequencing. NGS technologies provide fast and cost-effective sequencing strategies that can be used in various genetic applications; for example, in high-throughput mutation detection, small RNA detection, or the monitoring of epigenetic changes. The most well-known NGS technologies have been developed by Illumina (and Solexa, Inc, purchased by Illumina in 2007; San Diego, CA, USA), Helicos BioSciences (Cambridge, MA, USA), ABI/SOLiD, and 454 Life Sciences (a subsidiary of Roche; Branford, CT, USA) and use a single-molecule template for mutation detection with cloning-free approaches.190,191