Premium
Target enrichment and high‐throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond‐Blackfan anaemia
Author(s) -
Gerrard Gareth,
Valgañón Mikel,
Foong Hui En,
Kasperaviciute Dalia,
Iskander Deena,
Game Laurence,
Müller Michael,
Aitman Timothy J.,
Roberts Irene,
Fuente Josu,
Foroni Letizia,
Karadimitris Anastasios
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12397
Subject(s) - gene , dna sequencing , genetics , biology , mutation , ribosomal protein , diamond–blackfan anemia , ribosomal rna , computational biology , rna , ribosome
Summary 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 .