Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations

Sarah Vergult; Ellen Van Binsbergen; Tom Sante; Silke Nowak; Olivier Vanakker; Kathleen Claes; Bruce Poppe; Nathalie Van der Aa; Markus J van Roosmalen; Karen Duran; Masoumeh Tavakoli-Yaraki; Marielle Swinkels; Marie-José van den Boogaard; Mieke van Haelst; Filip Roelens; Frank Speleman; Edwin Cuppen; Geert Mortier; Wigard P Kloosterman; Björn Menten

doi:10.1038/ejhg.2013.220

Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations

Sarah Vergult, Ellen Van Binsbergen, Tom Sante, Silke Nowak, Olivier Vanakker, Kathleen Claes, Bruce Poppe, Nathalie Van der Aa, Markus J van Roosmalen, Karen Duran, Masoumeh Tavakoli-Yaraki, Marielle Swinkels, Marie-José van den Boogaard, Mieke van Haelst, Filip Roelens, Frank Speleman, Edwin Cuppen, Geert Mortier, Wigard P Kloosterman, Björn Menten

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

26 Citaten (Scopus)

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Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs.

Originele taal-2	Engels
Pagina's (van-tot)	652-9
Aantal pagina's	8
Tijdschrift	European Journal of Human Genetics
Volume	22
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1038/ejhg.2013.220
Status	Gepubliceerd - mei 2014

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Vergult, S., Van Binsbergen, E., Sante, T., Nowak, S., Vanakker, O., Claes, K., Poppe, B., Van der Aa, N., van Roosmalen, M. J., Duran, K., Tavakoli-Yaraki, M., Swinkels, M., van den Boogaard, M.-J., van Haelst, M., Roelens, F., Speleman, F., Cuppen, E., Mortier, G., Kloosterman, W. P., & Menten, B. (2014). Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations. European Journal of Human Genetics, 22(5), 652-9. https://doi.org/10.1038/ejhg.2013.220

@article{e37e8b5eda5d4cb490fd4c293d6546bd,

title = "Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations",

abstract = "Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs.",

keywords = "Abnormalities, Multiple, Chromosome Aberrations, Chromosome Banding, Chromosome Duplication, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 21, Comparative Genomic Hybridization, Computational Biology, Female, High-Throughput Nucleotide Sequencing, Humans, Intellectual Disability, Karyotype, Male, Recombination, Genetic",

author = "Sarah Vergult and {Van Binsbergen}, Ellen and Tom Sante and Silke Nowak and Olivier Vanakker and Kathleen Claes and Bruce Poppe and {Van der Aa}, Nathalie and {van Roosmalen}, {Markus J} and Karen Duran and Masoumeh Tavakoli-Yaraki and Marielle Swinkels and {van den Boogaard}, Marie-Jos{\'e} and {van Haelst}, Mieke and Filip Roelens and Frank Speleman and Edwin Cuppen and Geert Mortier and Kloosterman, {Wigard P} and Bj{\"o}rn Menten",

year = "2014",

month = may,

doi = "10.1038/ejhg.2013.220",

language = "English",

volume = "22",

pages = "652--9",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

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Vergult, S, Van Binsbergen, E, Sante, T, Nowak, S, Vanakker, O, Claes, K, Poppe, B, Van der Aa, N, van Roosmalen, MJ, Duran, K, Tavakoli-Yaraki, M, Swinkels, M, van den Boogaard, M-J, van Haelst, M, Roelens, F, Speleman, F, Cuppen, E, Mortier, G, Kloosterman, WP & Menten, B 2014, 'Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations', European Journal of Human Genetics, vol. 22, nr. 5, blz. 652-9. https://doi.org/10.1038/ejhg.2013.220

Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations. / Vergult, Sarah; Van Binsbergen, Ellen; Sante, Tom et al.
In: European Journal of Human Genetics, Vol. 22, Nr. 5, 05.2014, blz. 652-9.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

T1 - Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations

AU - Vergult, Sarah

AU - Van Binsbergen, Ellen

AU - Sante, Tom

AU - Nowak, Silke

AU - Vanakker, Olivier

AU - Claes, Kathleen

AU - Poppe, Bruce

AU - Van der Aa, Nathalie

AU - van Roosmalen, Markus J

AU - Duran, Karen

AU - Tavakoli-Yaraki, Masoumeh

AU - Swinkels, Marielle

AU - van den Boogaard, Marie-José

AU - van Haelst, Mieke

AU - Roelens, Filip

AU - Speleman, Frank

AU - Cuppen, Edwin

AU - Mortier, Geert

AU - Kloosterman, Wigard P

AU - Menten, Björn

PY - 2014/5

Y1 - 2014/5

N2 - Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs.

AB - Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs.

KW - Abnormalities, Multiple

KW - Chromosome Aberrations

KW - Chromosome Banding

KW - Chromosome Duplication

KW - Chromosomes, Human, Pair 18

KW - Chromosomes, Human, Pair 21

KW - Comparative Genomic Hybridization

KW - Computational Biology

KW - Female

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Intellectual Disability

KW - Karyotype

KW - Male

KW - Recombination, Genetic

U2 - 10.1038/ejhg.2013.220

DO - 10.1038/ejhg.2013.220

M3 - Article

C2 - 24105367

SN - 1018-4813

VL - 22

SP - 652

EP - 659

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 5

ER -

Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations

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