Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia

Gareth Gerrard, Mikel Valgañón, Hui En Foong, Dalia Kasperaviciute, Deena Iskander, Laurence Game, Michael Müller, Timothy J Aitman, Irene Roberts, Josu de la Fuente, Letizia Foroni, Anastasios Karadimitris

Research output: Contribution to journalArticlepeer-review

Abstract

Diamond-Blackfan anaemia (DBA) is caused by inactivating mutations in ribosomal protein (RP) genes, with mutations in 13 of the 80 RP genes accounting for 50-60% of cases. The remaining 40-50% cases may harbour mutations in one of the remaining RP genes, but the very low frequencies render conventional genetic screening as challenging. We, therefore, applied custom enrichment technology combined with high-throughput sequencing to screen all 80 RP genes. Using this approach, we identified and validated inactivating mutations in 15/17 (88%) DBA patients. Target enrichment combined with high-throughput sequencing is a robust and improved methodology for the genetic diagnosis of DBA.

Original languageEnglish
Pages (from-to)530-6
Number of pages7
JournalBritish journal of haematology
Volume162
Issue number4
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Adolescent
  • Adult
  • Anemia, Diamond-Blackfan
  • Child
  • Child, Preschool
  • Codon, Nonsense
  • DNA Mutational Analysis
  • DNA, Ribosomal
  • Female
  • Frameshift Mutation
  • Gene Library
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Ribosomal Proteins
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Deletion

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