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Article Dans Une Revue European Journal of Human Genetics Année : 2010

Experiences with array-based sequence capture; towards clinical applications

Résumé

Although sequencing of a human genome gradually becomes an option, zooming in on the region of interest remains attractive and cost saving. We performed array-based sequence capture using 385K NimbleGen arrays to zoom in on the protein-coding and immediate intron flanking sequences of 112 genes, potentially involved in mental retardation and congenital malformation. Captured material was sequenced using Illumina technology. A data analysis pipeline was built which detects sequence variants, positions them in relation to the gene, checks for presence in databases (e.g. dbSNP) and predicts the potential consequences at the level of RNA splicing and protein translation. In the samples analyzed all known variants were reliably detected, incl. pathogenic variants from control cases and SNPs derived from array experiments. Although overall coverage varied considerably, it was reproducible per region and facilitated the detection of large deletions and duplications (CNVs), incl. a partial deletion in the B3GALTL gene from a patient sample. For ultimate diagnostic application overall results need to be improved. Future arrays should contain probes from both DNA strands and to obtain a more even coverage one could add fewer probes from densely and more probes from sparsely covered regions.
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Dates et versions

hal-00580685 , version 1 (29-03-2011)

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Johan T den Dunnen, Rowida Almomani, Jaap van Der Heijden, Yavuz Ariyurek, Yuchig Lai, et al.. Experiences with array-based sequence capture; towards clinical applications. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.145⟩. ⟨hal-00580685⟩

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