Copy number variation detection and genotyping from exome sequence data
Niklas Krumm,Peter H. Sudmant,Arthur Ko,Brian J. O'Roak,Maika Malig,Bradley P. Coe,Aaron R. Quinlan,Deborah A. Nickerson,Evan E. Eichler +8 more
TL;DR: A novel method using singular value decomposition (SVD) normalization to discover rare genic copy number variants (CNVs) as well as genotype copy number polymorphic (CNP) loci with high sensitivity and specificity from exome sequencing data is developed.
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Abstract: While exome sequencing is readily amenable to single-nucleotide variant discovery, the sparse and nonuniform nature of the exome capture reaction has hindered exome-based detection and characterization of genic copy number variation. We developed a novel method using singular value decomposition (SVD) normalization to discover rare genic copy number variants (CNVs) as well as genotype copy number polymorphic (CNP) loci with high sensitivity and specificity from exome sequencing data. We estimate the precision of our algorithm using 122 trios (366 exomes) and show that this method can be used to reliably predict (94% overall precision) both de novo and inherited rare CNVs involving three or more consecutive exons. We demonstrate that exome-based genotyping of CNPs strongly correlates with whole-genome data (median r(2) = 0.91), especially for loci with fewer than eight copies, and can estimate the absolute copy number of multi-allelic genes with high accuracy (78% call level). The resulting user-friendly computational pipeline, CoNIFER (copy number inference from exome reads), can reliably be used to discover disruptive genic CNVs missed by standard approaches and should have broad application in human genetic studies of disease.
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Identification of a Complex Allele in IMPG2 as a Cause of Adult-Onset Vitelliform Macular Dystrophy
Irene Vázquez-Domínguez,Catherina H.Z. Li,Zeinab Fadaie,Lonneke Haer-Wigman,Frans P.M. Cremers,Alejandro Garanto,Carel B. Hoyng,Susanne Roosing +7 more
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Genetic profiling for risk reduction in human cardiovascular disease.
TL;DR: An overview of how genomic data is shaping the current understanding and treatment of cardiovascular disease is discussed.
EXOME REPORT: Novel mutation in ATP6V1B2 segregating with autosomal dominant epilepsy, intellectual disability and mild gingival and nail abnormalities.
Marie Shaw,Anna Winczewska-Wiktor,Magdalena Badura-Stronka,Sunita Koirala,Alison Gardner,Łukasz Kuszel,Piotr Kowal,Barbara Steinborn,Monika Starczewska,Sarah I. Garry,Ingrid E. Scheffer,Samuel F. Berkovic,Jozef Gecz +12 more
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Efficient detection of chromosome imbalances and single nucleotide variants using targeted sequencing in the clinical setting.
Darine Villela,Silvia S. Costa,Angela Maria Vianna-Morgante,Ana Cristina Victorino Krepischi,Carla Rosenberg +4 more
TL;DR: The data show that the combination of a sequencing platform comprising focused exome and whole genome backbone, with appropriate algorithms, enables a cost-effective and efficient solution for the simultaneous detection of CNVs and SNVs.
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Allele-specific copy number estimation by whole exome sequencing.
TL;DR: This work describes a method for estimating allele-specific copy number using whole exome sequencing data from tumor and matched normal to estimate allele- specific copy number in cancer genomics studies.
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