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

doi:10.1111/bjh.12397

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 journal › Article › peer-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 language	English
Pages (from-to)	530-6
Number of pages	7
Journal	British journal of haematology
Volume	162
Issue number	4
DOIs	https://doi.org/10.1111/bjh.12397
Publication status	Published - 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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10.1111/bjh.12397

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Gerrard, G., Valgañón, M., Foong, H. E., Kasperaviciute, D., Iskander, D., Game, L., Müller, M., Aitman, T. J., Roberts, I., de la Fuente, J., Foroni, L., & Karadimitris, A. (2013). Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. British journal of haematology, 162(4), 530-6. https://doi.org/10.1111/bjh.12397

@article{3050c4e44309445b989ebe78f7eab2d6,

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

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.",

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",

author = "Gareth Gerrard and Mikel Valga{\~n}{\'o}n and Foong, {Hui En} and Dalia Kasperaviciute and Deena Iskander and Laurence Game and Michael M{\"u}ller and Aitman, {Timothy J} and Irene Roberts and {de la Fuente}, Josu and Letizia Foroni and Anastasios Karadimitris",

note = "{\textcopyright} 2013 John Wiley & Sons Ltd.",

year = "2013",

month = aug,

doi = "10.1111/bjh.12397",

language = "English",

volume = "162",

pages = "530--6",

journal = "British journal of haematology",

issn = "0007-1048",

publisher = "Wiley-Blackwell",

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Gerrard, G, Valgañón, M, Foong, HE, Kasperaviciute, D, Iskander, D, Game, L, Müller, M, Aitman, TJ, Roberts, I, de la Fuente, J, Foroni, L & Karadimitris, A 2013, 'Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia', British journal of haematology, vol. 162, no. 4, pp. 530-6. https://doi.org/10.1111/bjh.12397

TY - JOUR

T1 - Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia

AU - Gerrard, Gareth

AU - Valgañón, Mikel

AU - Foong, Hui En

AU - Kasperaviciute, Dalia

AU - Iskander, Deena

AU - Game, Laurence

AU - Müller, Michael

AU - Aitman, Timothy J

AU - Roberts, Irene

AU - de la Fuente, Josu

AU - Foroni, Letizia

AU - Karadimitris, Anastasios

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Anemia, Diamond-Blackfan

KW - Child

KW - Child, Preschool

KW - Codon, Nonsense

KW - DNA Mutational Analysis

KW - DNA, Ribosomal

KW - Female

KW - Frameshift Mutation

KW - Gene Library

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Male

KW - Ribosomal Proteins

KW - Sequence Alignment

KW - Sequence Analysis, DNA

KW - Sequence Deletion

U2 - 10.1111/bjh.12397

DO - 10.1111/bjh.12397

M3 - Article

C2 - 23718193

VL - 162

SP - 530

EP - 536

JO - British journal of haematology

JF - British journal of haematology

SN - 0007-1048

IS - 4

ER -

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

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Keywords

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