A dyadic approach to the delineation of diagnostic entities in clinical genomics

Leslie G. Biesecker; Margaret P. Adam; Fowzan S. Alkuraya; Anne R. Amemiya; Michael J. Bamshad; Anita E. Beck; James T. Bennett; Lynne M. Bird; John C. Carey; Brian Chung; Robin D. Clark; Timothy C. Cox; Cynthia Curry; Mary Beth Palko Dinulos; William B. Dobyns; Philip F. Giampietro; Katta M. Girisha; Ian A. Glass; John M. Graham; Karen W. Gripp; Chad R. Haldeman-Englert; Bryan D. Hall; A. Micheil Innes; Jennifer M. Kalish; Kim M. Keppler-Noreuil; Kenjiro Kosaki; Beth A. Kozel; Ghayda M. Mirzaa; John J. Mulvihill; Malgorzata J.M. Nowaczyk; Roberta A. Pagon; Kyle Retterer; Alan F. Rope; Pedro A. Sanchez-Lara; Laurie H. Seaver; Joseph T. Shieh; Anne M. Slavotinek; Andrew K. Sobering; Cathy A. Stevens; David A. Stevenson; Tiong Yang Tan; Wen Hann Tan; Anne C. Tsai; David D. Weaver; Marc S. Williams; Elaine Zackai; Yuri A. Zarate

doi:10.1016/j.ajhg.2020.11.013

A dyadic approach to the delineation of diagnostic entities in clinical genomics

Leslie G. Biesecker^*
, Margaret P. Adam
, Fowzan S. Alkuraya
, Anne R. Amemiya
, Michael J. Bamshad
, Anita E. Beck
, James T. Bennett
, Lynne M. Bird
, John C. Carey
, Brian Chung
, Robin D. Clark
, Timothy C. Cox
, Cynthia Curry
, Mary Beth Palko Dinulos
, William B. Dobyns
, Philip F. Giampietro
, Katta M. Girisha
, Ian A. Glass
, John M. Graham
, Karen W. Gripp

Chad R. Haldeman-Englert, Bryan D. Hall, A. Micheil Innes, Jennifer M. Kalish, Kim M. Keppler-Noreuil, Kenjiro Kosaki, Beth A. Kozel, Ghayda M. Mirzaa, John J. Mulvihill, Malgorzata J.M. Nowaczyk, Roberta A. Pagon, Kyle Retterer, Alan F. Rope, Pedro A. Sanchez-Lara, Laurie H. Seaver, Joseph T. Shieh, Anne M. Slavotinek, Andrew K. Sobering, Cathy A. Stevens, David A. Stevenson, Tiong Yang Tan, Wen Hann Tan, Anne C. Tsai, David D. Weaver, Marc S. Williams, Elaine Zackai, Yuri A. Zarate

^*Corresponding author for this work

Department of Medical Genetics, Kasturba Medical College, Manipal

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

101 Citations (Scopus)

Abstract

The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as “GENE-related phenotype descriptor” (e.g., “CFTR-related cystic fibrosis”). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.

Original language	English
Pages (from-to)	8-15
Number of pages	8
Journal	American Journal of Human Genetics
Volume	108
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2020.11.013
Publication status	Published - 07-01-2021

All Science Journal Classification (ASJC) codes

Genetics
Genetics(clinical)

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10.1016/j.ajhg.2020.11.013

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Biesecker, L. G., Adam, M. P., Alkuraya, F. S., Amemiya, A. R., Bamshad, M. J., Beck, A. E., Bennett, J. T., Bird, L. M., Carey, J. C., Chung, B., Clark, R. D., Cox, T. C., Curry, C., Dinulos, M. B. P., Dobyns, W. B., Giampietro, P. F., Girisha, K. M., Glass, I. A., Graham, J. M., ... Zarate, Y. A. (2021). A dyadic approach to the delineation of diagnostic entities in clinical genomics. American Journal of Human Genetics, 108(1), 8-15. https://doi.org/10.1016/j.ajhg.2020.11.013

@article{503b9654154c4c1286a990c68386b930,

title = "A dyadic approach to the delineation of diagnostic entities in clinical genomics",

abstract = "The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as “GENE-related phenotype descriptor” (e.g., “CFTR-related cystic fibrosis”). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.",

author = "Biesecker, \{Leslie G.\} and Adam, \{Margaret P.\} and Alkuraya, \{Fowzan S.\} and Amemiya, \{Anne R.\} and Bamshad, \{Michael J.\} and Beck, \{Anita E.\} and Bennett, \{James T.\} and Bird, \{Lynne M.\} and Carey, \{John C.\} and Brian Chung and Clark, \{Robin D.\} and Cox, \{Timothy C.\} and Cynthia Curry and Dinulos, \{Mary Beth Palko\} and Dobyns, \{William B.\} and Giampietro, \{Philip F.\} and Girisha, \{Katta M.\} and Glass, \{Ian A.\} and Graham, \{John M.\} and Gripp, \{Karen W.\} and Haldeman-Englert, \{Chad R.\} and Hall, \{Bryan D.\} and Innes, \{A. Micheil\} and Kalish, \{Jennifer M.\} and Keppler-Noreuil, \{Kim M.\} and Kenjiro Kosaki and Kozel, \{Beth A.\} and Mirzaa, \{Ghayda M.\} and Mulvihill, \{John J.\} and Nowaczyk, \{Malgorzata J.M.\} and Pagon, \{Roberta A.\} and Kyle Retterer and Rope, \{Alan F.\} and Sanchez-Lara, \{Pedro A.\} and Seaver, \{Laurie H.\} and Shieh, \{Joseph T.\} and Slavotinek, \{Anne M.\} and Sobering, \{Andrew K.\} and Stevens, \{Cathy A.\} and Stevenson, \{David A.\} and Tan, \{Tiong Yang\} and Tan, \{Wen Hann\} and Tsai, \{Anne C.\} and Weaver, \{David D.\} and Williams, \{Marc S.\} and Elaine Zackai and Zarate, \{Yuri A.\}",

note = "Funding Information: The authors thank Robert L. Nussbaum for critical review of a draft of this manuscript. L.G.B. was supported by the National Institutes of Health (NIH) ( ZIA HG200388 06 ). M.P.A., A.R.A., and R.A.P. are supported by a subcontract from Computercraft Corporation to the University of Washington for editing GeneReviews. T.C.C. was supported by NIH R01 DE027879 . J.M.K. was supported by Alex{\textquoteright}s Lemonade Stand Foundation , Damon Runyon Cancer Research Foundation , and NIH K08CA193915 . G.M.M. was supported by NIH K08NS092898 and Jordan{\textquoteright}s Guardian Angels and the Brotman Baty Institute . Publisher Copyright: {\textcopyright} 2020 American Society of Human Genetics Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2021",

month = jan,

day = "7",

doi = "10.1016/j.ajhg.2020.11.013",

language = "English",

volume = "108",

pages = "8--15",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

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Biesecker, LG, Adam, MP, Alkuraya, FS, Amemiya, AR, Bamshad, MJ, Beck, AE, Bennett, JT, Bird, LM, Carey, JC, Chung, B, Clark, RD, Cox, TC, Curry, C, Dinulos, MBP, Dobyns, WB, Giampietro, PF, Girisha, KM, Glass, IA, Graham, JM, Gripp, KW, Haldeman-Englert, CR, Hall, BD, Innes, AM, Kalish, JM, Keppler-Noreuil, KM, Kosaki, K, Kozel, BA, Mirzaa, GM, Mulvihill, JJ, Nowaczyk, MJM, Pagon, RA, Retterer, K, Rope, AF, Sanchez-Lara, PA, Seaver, LH, Shieh, JT, Slavotinek, AM, Sobering, AK, Stevens, CA, Stevenson, DA, Tan, TY, Tan, WH, Tsai, AC, Weaver, DD, Williams, MS, Zackai, E & Zarate, YA 2021, 'A dyadic approach to the delineation of diagnostic entities in clinical genomics', American Journal of Human Genetics, vol. 108, no. 1, pp. 8-15. https://doi.org/10.1016/j.ajhg.2020.11.013

TY - JOUR

T1 - A dyadic approach to the delineation of diagnostic entities in clinical genomics

AU - Biesecker, Leslie G.

AU - Adam, Margaret P.

AU - Alkuraya, Fowzan S.

AU - Amemiya, Anne R.

AU - Bamshad, Michael J.

AU - Beck, Anita E.

AU - Bennett, James T.

AU - Bird, Lynne M.

AU - Carey, John C.

AU - Chung, Brian

AU - Clark, Robin D.

AU - Cox, Timothy C.

AU - Curry, Cynthia

AU - Dinulos, Mary Beth Palko

AU - Dobyns, William B.

AU - Giampietro, Philip F.

AU - Girisha, Katta M.

AU - Glass, Ian A.

AU - Graham, John M.

AU - Gripp, Karen W.

AU - Haldeman-Englert, Chad R.

AU - Hall, Bryan D.

AU - Innes, A. Micheil

AU - Kalish, Jennifer M.

AU - Keppler-Noreuil, Kim M.

AU - Kosaki, Kenjiro

AU - Kozel, Beth A.

AU - Mirzaa, Ghayda M.

AU - Mulvihill, John J.

AU - Nowaczyk, Malgorzata J.M.

AU - Pagon, Roberta A.

AU - Retterer, Kyle

AU - Rope, Alan F.

AU - Sanchez-Lara, Pedro A.

AU - Seaver, Laurie H.

AU - Shieh, Joseph T.

AU - Slavotinek, Anne M.

AU - Sobering, Andrew K.

AU - Stevens, Cathy A.

AU - Stevenson, David A.

AU - Tan, Tiong Yang

AU - Tan, Wen Hann

AU - Tsai, Anne C.

AU - Weaver, David D.

AU - Williams, Marc S.

AU - Zackai, Elaine

AU - Zarate, Yuri A.

N1 - Funding Information: The authors thank Robert L. Nussbaum for critical review of a draft of this manuscript. L.G.B. was supported by the National Institutes of Health (NIH) ( ZIA HG200388 06 ). M.P.A., A.R.A., and R.A.P. are supported by a subcontract from Computercraft Corporation to the University of Washington for editing GeneReviews. T.C.C. was supported by NIH R01 DE027879 . J.M.K. was supported by Alex’s Lemonade Stand Foundation , Damon Runyon Cancer Research Foundation , and NIH K08CA193915 . G.M.M. was supported by NIH K08NS092898 and Jordan’s Guardian Angels and the Brotman Baty Institute . Publisher Copyright: © 2020 American Society of Human Genetics Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/1/7

Y1 - 2021/1/7

N2 - The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as “GENE-related phenotype descriptor” (e.g., “CFTR-related cystic fibrosis”). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.

AB - The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as “GENE-related phenotype descriptor” (e.g., “CFTR-related cystic fibrosis”). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.

UR - https://www.scopus.com/pages/publications/85098978703

UR - https://www.scopus.com/pages/publications/85098978703#tab=citedBy

U2 - 10.1016/j.ajhg.2020.11.013

DO - 10.1016/j.ajhg.2020.11.013

M3 - Review article

AN - SCOPUS:85098978703

SN - 0002-9297

VL - 108

SP - 8

EP - 15

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

A dyadic approach to the delineation of diagnostic entities in clinical genomics

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