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The Human Genome Project has opened the door to personalized medicine, provided that human genetic diversity can be analyzed in a high-throughput and cost-effective way. Illumina has developed a genotyping system that combines very high throughput and accuracy with low cost per SNP analysis. The system uses our BeadArray platform, a high level of multiplexing, and modular, scalable automation to meet the requirements for costeffective, genome-wide linkage disequilibrium studies. As implemented in a high-throughput genotyping service facility at Illumina, the system has a current capacity of one million SNP assays per day and is easily expandable. Each SNP call is associated with a quality score that correlates with accuracy.

ObjectiveTo develop a novel prenatal assay based on selective analysis of cell-free DNA in maternal blood for evaluation of fetal Trisomy 21 (T21) and Trisomy 18 (T18).MethodsTwo hundred ninety-eight pregnancies, including 39 T21 and seven T18 confirmed fetal aneuploidies, were analyzed using a novel, highly multiplexed assay, termed digital analysis of selected regions (DANSR™). Cell-free DNA from maternal blood samples was analyzed using DANSR assays for loci on chromosomes 21 and 18. Products from 96 separate patients were pooled and sequenced together. A standard Z-test of chromosomal proportions was used to distinguish aneuploid samples from average-risk pregnancy samples. DANSR aneuploidy discrimination was evaluated at various sequence depths.ResultsAt the lowest sequencing depth, corresponding to 204 000 sequencing counts per sample, average-risk cases where distinguished from T21 and T18 cases, with Z statistics for all cases exceeding 3.6. Increasing the sequencing depth to 410 000 counts per sample substantially improved separation of aneuploid and average-risk cases. A further increase to 620 000 counts per sample resulted in only marginal improvement. This depth of sequencing represents less than 5% of that required by massively parallel shotgun sequencing approaches.ConclusionDigital analysis of selected regions enables highly accurate, cost efficient, and scalable noninvasive fetal aneuploidy assessment. © 2012 John Wiley & Sons, Ltd.

BackgroundA high-quality reference genome assembly is a valuable tool for the study of non-model organisms. Genomic techniques can provide important insights about past population sizes and local adaptation and can aid in the development of breeding management plans. This information is important for fields such as conservation genetics, where endangered species require critical and immediate attention. However, funding for genomic-based methods can be sparse for conservation projects, as costs for general species management can consume budgets.FindingsHere, we report the generation of high-quality reference genomes for the African wild dog (Lycaon pictus) at a low cost (<$3000), thereby facilitating future studies of this endangered canid. We generated assemblies for three individuals using the linked-read 10x Genomics Chromium system. The most continuous assembly had a scaffold and contig N50 of 21 Mb and 83 Kb, respectively, and completely reconstructed 95% of a set of conserved mammalian genes. Additionally, we estimate the heterozygosity and demographic history of African wild dogs, revealing that although they have historically low effective population sizes, heterozygosity remains high.ConclusionsWe show that 10x Genomics Chromium data can be used to effectively generate high-quality genomes from Illumina short-read data of intermediate coverage (∼25x–50x). Interestingly, the wild dog shows higher heterozygosity than other species of conservation concern, possibly due to its behavioral ecology. The availability of reference genomes for non-model organisms will facilitate better genetic monitoring of threatened species such as the African wild dog and help conservationists to better understand the ecology and adaptability of those species in a changing environment.

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