The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

Lusine Nazaryan; Eunice G Stefanou; Claus Hansen; Nadezda Kosyakova; Mads Bak; Freddie H Sharkey; Theodora Mantziou; Anastasios D Papanastasiou; Voula Velissariou; Thomas Liehr; Maria Syrrou; Niels Tommerup

doi:10.1038/ejhg.2013.147

The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

Lusine Nazaryan, Eunice G Stefanou, Claus Hansen, Nadezda Kosyakova, Mads Bak, Freddie H Sharkey, Theodora Mantziou, Anastasios D Papanastasiou, Voula Velissariou, Thomas Liehr, Maria Syrrou, Niels Tommerup

Medical Genetics Program

37 Citations (Scopus)

Abstract

Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.

Original language	English
Journal	European Journal of Human Genetics
Volume	22
Issue number	3
Pages (from-to)	338-343
Number of pages	6
ISSN	1018-4813
DOIs	https://doi.org/10.1038/ejhg.2013.147
Publication status	Published - Mar 2014

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http://www.nature.com/ejhg/journal/v22/n3/full/ejhg2013147a.html

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Nazaryan, L., Stefanou, E. G., Hansen, C., Kosyakova, N., Bak, M., Sharkey, F. H., Mantziou, T., Papanastasiou, A. D., Velissariou, V., Liehr, T., Syrrou, M., & Tommerup, N. (2014). The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2. European Journal of Human Genetics, 22(3), 338-343. https://doi.org/10.1038/ejhg.2013.147

The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2. / Nazaryan, Lusine; Stefanou, Eunice G; Hansen, Claus et al.
In: European Journal of Human Genetics, Vol. 22, No. 3, 03.2014, p. 338-343.

Research output: Contribution to journal › Journal article › Research › peer-review

Nazaryan, L, Stefanou, EG, Hansen, C, Kosyakova, N, Bak, M, Sharkey, FH, Mantziou, T, Papanastasiou, AD, Velissariou, V, Liehr, T, Syrrou, M & Tommerup, N 2014, 'The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2', European Journal of Human Genetics, vol. 22, no. 3, pp. 338-343. https://doi.org/10.1038/ejhg.2013.147

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title = "The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2",

abstract = "Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.",

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AU - Nazaryan, Lusine

AU - Stefanou, Eunice G

AU - Hansen, Claus

AU - Kosyakova, Nadezda

AU - Bak, Mads

AU - Sharkey, Freddie H

AU - Mantziou, Theodora

AU - Papanastasiou, Anastasios D

AU - Velissariou, Voula

AU - Liehr, Thomas

AU - Syrrou, Maria

AU - Tommerup, Niels

PY - 2014/3

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N2 - Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.

AB - Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.

U2 - 10.1038/ejhg.2013.147

DO - 10.1038/ejhg.2013.147

M3 - Journal article

C2 - 23860044

SN - 1018-4813

VL - 22

SP - 338

EP - 343

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 3

ER -

The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

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