A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation

Patrick S. Tarpey; Raffaella Smith; Erin Pleasance; Annabel Whibley; Sarah Edkins; Claire Hardy; Sarah O'Meara; Calli Latimer; Ed Dicks; Andrew Menzies; Phil Stephens; Matt Blow; Christopher Greenman; Yali Xue; Chris Tyler-Smith; Deborah Thompson; Kristian Gray; Jenny Andrews; Syd Barthorpe; Gemma Buck; Jennifer Cole; Rebecca Dunmore; David Jones; Mark Maddison; Tatiana Mironenko; Rachel Turner; Kelly Turrell; Jennifer Varian; Sofie West; Sara Widaa; Paul Wray; Jon Teague; Adam Butler; Andrew Jenkinson; Mingming Jia; David Richardson; Rebecca Shepherd; Richard Wooster; M. Isabel Tejada; Francisco Martinez; Gemma Carvill; Rene Goliath; Arjan P. M. de Brouwer; Hans van Bokhoven; Hilde van Esch; Jamel Chelly; Martine Raynaud; Hans-Hilger Ropers; Fatima E. Abidi; Anand K. Srivastava; James Cox; Ying Luo; Uma Mallya; Jenny Moon; Josef Parnau; Shehla Mohammed; John L. Tolmie; Cheryl Shoubridge; Mark Corbett; Alison Gardner; Eric Haan; Sinitdhorn Rujirabanjerd; Marie Shaw; Lucianne Vandeleur; Tod Fullston; Douglas F. Easton; Jackie Boyle; Michael Partington; Anna Hackett; Michael Field; Cindy Skinner; Roger E. Stevenson; Martin Bobrow; Gillian Turner; Charles E. Schwartz; Jozef Gecz; F. Lucy Raymond; P. Andrew Futreal; Michael R. Stratton

doi:10.1038/ng.367

A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation

Patrick S. Tarpey, Raffaella Smith, Erin Pleasance, Annabel Whibley, Sarah Edkins, Claire Hardy, Sarah O'Meara, Calli Latimer, Ed Dicks, Andrew Menzies, Phil Stephens, Matt Blow, Christopher Greenman, Yali Xue, Chris Tyler-Smith, Deborah Thompson, Kristian Gray, Jenny Andrews, Syd Barthorpe, Gemma BuckJennifer Cole, Rebecca Dunmore, David Jones, Mark Maddison, Tatiana Mironenko, Rachel Turner, Kelly Turrell, Jennifer Varian, Sofie West, Sara Widaa, Paul Wray, Jon Teague, Adam Butler, Andrew Jenkinson, Mingming Jia, David Richardson, Rebecca Shepherd, Richard Wooster, M. Isabel Tejada, Francisco Martinez, Gemma Carvill, Rene Goliath, Arjan P. M. de Brouwer, Hans van Bokhoven, Hilde van Esch, Jamel Chelly, Martine Raynaud, Hans-Hilger Ropers, Fatima E. Abidi, Anand K. Srivastava, James Cox, Ying Luo, Uma Mallya, Jenny Moon, Josef Parnau, Shehla Mohammed, John L. Tolmie, Cheryl Shoubridge, Mark Corbett, Alison Gardner, Eric Haan, Sinitdhorn Rujirabanjerd, Marie Shaw, Lucianne Vandeleur, Tod Fullston, Douglas F. Easton, Jackie Boyle, Michael Partington, Anna Hackett, Michael Field, Cindy Skinner, Roger E. Stevenson, Martin Bobrow, Gillian Turner, Charles E. Schwartz, Jozef Gecz, F. Lucy Raymond, P. Andrew Futreal, Michael R. Stratton

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Abstract

Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR), the largest direct screen for constitutional disease-causing mutations thus far reported. The screen has discovered nine genes implicated in XLMR, including SYP, ZNF711 and CASK reported here, confirming the power of this strategy. The study has, however, also highlighted issues confronting whole-genome sequencing screens, including the observation that loss of function of 1% or more of X-chromosome genes is compatible with apparently normal existence.

Original language	English
Pages (from-to)	535-543
Number of pages	9
Journal	Nature Genetics
Volume	41
Issue number	5
Early online date	19 Apr 2009
DOIs	https://doi.org/10.1038/ng.367
Publication status	Published - May 2009

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Cite this

Tarpey, P. S., Smith, R., Pleasance, E., Whibley, A., Edkins, S., Hardy, C., O'Meara, S., Latimer, C., Dicks, E., Menzies, A., Stephens, P., Blow, M., Greenman, C., Xue, Y., Tyler-Smith, C., Thompson, D., Gray, K., Andrews, J., Barthorpe, S., ... Stratton, M. R. (2009). A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nature Genetics, 41(5), 535-543. https://doi.org/10.1038/ng.367

@article{964c9c19d9354fbfb3a6ad6bfeb8af49,

title = "A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation",

abstract = "Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR), the largest direct screen for constitutional disease-causing mutations thus far reported. The screen has discovered nine genes implicated in XLMR, including SYP, ZNF711 and CASK reported here, confirming the power of this strategy. The study has, however, also highlighted issues confronting whole-genome sequencing screens, including the observation that loss of function of 1% or more of X-chromosome genes is compatible with apparently normal existence.",

author = "Tarpey, {Patrick S.} and Raffaella Smith and Erin Pleasance and Annabel Whibley and Sarah Edkins and Claire Hardy and Sarah O'Meara and Calli Latimer and Ed Dicks and Andrew Menzies and Phil Stephens and Matt Blow and Christopher Greenman and Yali Xue and Chris Tyler-Smith and Deborah Thompson and Kristian Gray and Jenny Andrews and Syd Barthorpe and Gemma Buck and Jennifer Cole and Rebecca Dunmore and David Jones and Mark Maddison and Tatiana Mironenko and Rachel Turner and Kelly Turrell and Jennifer Varian and Sofie West and Sara Widaa and Paul Wray and Jon Teague and Adam Butler and Andrew Jenkinson and Mingming Jia and David Richardson and Rebecca Shepherd and Richard Wooster and Tejada, {M. Isabel} and Francisco Martinez and Gemma Carvill and Rene Goliath and {de Brouwer}, {Arjan P. M.} and {van Bokhoven}, Hans and {van Esch}, Hilde and Jamel Chelly and Martine Raynaud and Hans-Hilger Ropers and Abidi, {Fatima E.} and Srivastava, {Anand K.} and James Cox and Ying Luo and Uma Mallya and Jenny Moon and Josef Parnau and Shehla Mohammed and Tolmie, {John L.} and Cheryl Shoubridge and Mark Corbett and Alison Gardner and Eric Haan and Sinitdhorn Rujirabanjerd and Marie Shaw and Lucianne Vandeleur and Tod Fullston and Easton, {Douglas F.} and Jackie Boyle and Michael Partington and Anna Hackett and Michael Field and Cindy Skinner and Stevenson, {Roger E.} and Martin Bobrow and Gillian Turner and Schwartz, {Charles E.} and Jozef Gecz and Raymond, {F. Lucy} and Futreal, {P. Andrew} and Stratton, {Michael R.}",

note = "Funding information: The work was supported by the European Community's Seventh Framework Programme-the GEN2PHEN Project, the New South Wales Department of Health, the Australian NHMRC, the SMILE foundation, the WCH Foundation, D. Harwood, EU grant QLG3-CT- 2002-01810 (EURO-MRX), US National Institutes of Health (HD26202) to C.E.S., the South Carolina Department of Disabilities and Special Needs (SCDDSN), Action Medical Research and the Wellcome Trust.",

year = "2009",

month = may,

doi = "10.1038/ng.367",

language = "English",

volume = "41",

pages = "535--543",

journal = "Nature Genetics",

issn = "1061-4036",

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Tarpey, PS, Smith, R, Pleasance, E, Whibley, A, Edkins, S, Hardy, C, O'Meara, S, Latimer, C, Dicks, E, Menzies, A, Stephens, P, Blow, M, Greenman, C, Xue, Y, Tyler-Smith, C, Thompson, D, Gray, K, Andrews, J, Barthorpe, S, Buck, G, Cole, J, Dunmore, R, Jones, D, Maddison, M, Mironenko, T, Turner, R, Turrell, K, Varian, J, West, S, Widaa, S, Wray, P, Teague, J, Butler, A, Jenkinson, A, Jia, M, Richardson, D, Shepherd, R, Wooster, R, Tejada, MI, Martinez, F, Carvill, G, Goliath, R, de Brouwer, APM, van Bokhoven, H, van Esch, H, Chelly, J, Raynaud, M, Ropers, H-H, Abidi, FE, Srivastava, AK, Cox, J, Luo, Y, Mallya, U, Moon, J, Parnau, J, Mohammed, S, Tolmie, JL, Shoubridge, C, Corbett, M, Gardner, A, Haan, E, Rujirabanjerd, S, Shaw, M, Vandeleur, L, Fullston, T, Easton, DF, Boyle, J, Partington, M, Hackett, A, Field, M, Skinner, C, Stevenson, RE, Bobrow, M, Turner, G, Schwartz, CE, Gecz, J, Raymond, FL, Futreal, PA & Stratton, MR 2009, 'A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation', Nature Genetics, vol. 41, no. 5, pp. 535-543. https://doi.org/10.1038/ng.367

TY - JOUR

T1 - A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation

AU - Tarpey, Patrick S.

AU - Smith, Raffaella

AU - Pleasance, Erin

AU - Whibley, Annabel

AU - Edkins, Sarah

AU - Hardy, Claire

AU - O'Meara, Sarah

AU - Latimer, Calli

AU - Dicks, Ed

AU - Menzies, Andrew

AU - Stephens, Phil

AU - Blow, Matt

AU - Greenman, Christopher

AU - Xue, Yali

AU - Tyler-Smith, Chris

AU - Thompson, Deborah

AU - Gray, Kristian

AU - Andrews, Jenny

AU - Barthorpe, Syd

AU - Buck, Gemma

AU - Cole, Jennifer

AU - Dunmore, Rebecca

AU - Jones, David

AU - Maddison, Mark

AU - Mironenko, Tatiana

AU - Turner, Rachel

AU - Turrell, Kelly

AU - Varian, Jennifer

AU - West, Sofie

AU - Widaa, Sara

AU - Wray, Paul

AU - Teague, Jon

AU - Butler, Adam

AU - Jenkinson, Andrew

AU - Jia, Mingming

AU - Richardson, David

AU - Shepherd, Rebecca

AU - Wooster, Richard

AU - Tejada, M. Isabel

AU - Martinez, Francisco

AU - Carvill, Gemma

AU - Goliath, Rene

AU - de Brouwer, Arjan P. M.

AU - van Bokhoven, Hans

AU - van Esch, Hilde

AU - Chelly, Jamel

AU - Raynaud, Martine

AU - Ropers, Hans-Hilger

AU - Abidi, Fatima E.

AU - Srivastava, Anand K.

AU - Cox, James

AU - Luo, Ying

AU - Mallya, Uma

AU - Moon, Jenny

AU - Parnau, Josef

AU - Mohammed, Shehla

AU - Tolmie, John L.

AU - Shoubridge, Cheryl

AU - Corbett, Mark

AU - Gardner, Alison

AU - Haan, Eric

AU - Rujirabanjerd, Sinitdhorn

AU - Shaw, Marie

AU - Vandeleur, Lucianne

AU - Fullston, Tod

AU - Easton, Douglas F.

AU - Boyle, Jackie

AU - Partington, Michael

AU - Hackett, Anna

AU - Field, Michael

AU - Skinner, Cindy

AU - Stevenson, Roger E.

AU - Bobrow, Martin

AU - Turner, Gillian

AU - Schwartz, Charles E.

AU - Gecz, Jozef

AU - Raymond, F. Lucy

AU - Futreal, P. Andrew

AU - Stratton, Michael R.

N1 - Funding information: The work was supported by the European Community's Seventh Framework Programme-the GEN2PHEN Project, the New South Wales Department of Health, the Australian NHMRC, the SMILE foundation, the WCH Foundation, D. Harwood, EU grant QLG3-CT- 2002-01810 (EURO-MRX), US National Institutes of Health (HD26202) to C.E.S., the South Carolina Department of Disabilities and Special Needs (SCDDSN), Action Medical Research and the Wellcome Trust.

PY - 2009/5

Y1 - 2009/5

N2 - Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR), the largest direct screen for constitutional disease-causing mutations thus far reported. The screen has discovered nine genes implicated in XLMR, including SYP, ZNF711 and CASK reported here, confirming the power of this strategy. The study has, however, also highlighted issues confronting whole-genome sequencing screens, including the observation that loss of function of 1% or more of X-chromosome genes is compatible with apparently normal existence.

AB - Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR), the largest direct screen for constitutional disease-causing mutations thus far reported. The screen has discovered nine genes implicated in XLMR, including SYP, ZNF711 and CASK reported here, confirming the power of this strategy. The study has, however, also highlighted issues confronting whole-genome sequencing screens, including the observation that loss of function of 1% or more of X-chromosome genes is compatible with apparently normal existence.

U2 - 10.1038/ng.367

DO - 10.1038/ng.367

M3 - Article

VL - 41

SP - 535

EP - 543

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -