Genomics

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Exome sequencing to identify predisposition to Wilms tumour


ABSTRACT: To identify new Wilms tumor predisposition genes, we performed whole-exome paired-end sequencing of lymphocyte DNA from 12 affected individuals from six unrelated, non-syndromic Wilms tumor families in which known causes had been excluded. We prepared DNA libraries from 1.5 mg blood-derived genomic DNA using the Paired-End DNA Sample Preparation Kit (Ilumina). DNA was fragmented using Covaris technology and the libraries were prepared without gel size selection. We performed target enrichment using the TruSeq Exome Enrichment Kit (Illumina) by targeting 62 mb of the human genome. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 generating 2?101 bp reads.

PROVIDER: EGAS00001000904 | EGA |

REPOSITORIES: EGA

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Publications


Wilms tumour is a childhood kidney cancer. Here we identify inactivating CTR9 mutations in 3 of 35 Wilms tumour families, through exome and Sanger sequencing. By contrast, no similar mutations are present in 1,000 population controls (P<0.0001). Each mutation segregates with Wilms tumour in the family and a second mutational event is present in available tumours. CTR9 is a key component of the polymerase-associated factor 1 complex which has multiple roles in RNA polymerase II regulation and is  ...[more]

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