Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation

The dilemma of how to categorize and classify diseases has been debated for centuries. The field of medical genetics has historically approached nosology based on clinical phenotypes observed in patients and families. Advances in genomic sequencing and understanding of genetic contributions to disea...

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Autores principales: Thaxton, Courtney, Goldstein, Jennifer, DiStefano, Marina, Wallace, Kathleen, Witmer, P. Dane, Haendel, Melissa A., Hamosh, Ada, Rehm, Heidi L., Berg, Jonathan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221396/
https://www.ncbi.nlm.nih.gov/pubmed/35754516
http://dx.doi.org/10.1016/j.xgen.2022.100131
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author Thaxton, Courtney
Goldstein, Jennifer
DiStefano, Marina
Wallace, Kathleen
Witmer, P. Dane
Haendel, Melissa A.
Hamosh, Ada
Rehm, Heidi L.
Berg, Jonathan S.
author_facet Thaxton, Courtney
Goldstein, Jennifer
DiStefano, Marina
Wallace, Kathleen
Witmer, P. Dane
Haendel, Melissa A.
Hamosh, Ada
Rehm, Heidi L.
Berg, Jonathan S.
author_sort Thaxton, Courtney
collection PubMed
description The dilemma of how to categorize and classify diseases has been debated for centuries. The field of medical genetics has historically approached nosology based on clinical phenotypes observed in patients and families. Advances in genomic sequencing and understanding of genetic contributions to disease often provoke a need to reassess these classifications. The Clinical Genome Resource (ClinGen) has developed frameworks to classify the strength of evidence underlying monogenic gene-disease relationships, variant pathogenicity, and clinical actionability. It is therefore necessary to define the disease entity being evaluated, which can be challenging for genes associated with multiple conditions and/or a broad phenotypic spectrum. We therefore developed criteria to guide “lumping and splitting” decisions and improve consistency in defining monogenic gene-disease relationships. Here, we outline the precuration process, the lumping and splitting guidelines with examples, and describe the implications for clinical diagnosis, informatics, and care management.
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spelling pubmed-92213962022-06-23 Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation Thaxton, Courtney Goldstein, Jennifer DiStefano, Marina Wallace, Kathleen Witmer, P. Dane Haendel, Melissa A. Hamosh, Ada Rehm, Heidi L. Berg, Jonathan S. Cell Genom Article The dilemma of how to categorize and classify diseases has been debated for centuries. The field of medical genetics has historically approached nosology based on clinical phenotypes observed in patients and families. Advances in genomic sequencing and understanding of genetic contributions to disease often provoke a need to reassess these classifications. The Clinical Genome Resource (ClinGen) has developed frameworks to classify the strength of evidence underlying monogenic gene-disease relationships, variant pathogenicity, and clinical actionability. It is therefore necessary to define the disease entity being evaluated, which can be challenging for genes associated with multiple conditions and/or a broad phenotypic spectrum. We therefore developed criteria to guide “lumping and splitting” decisions and improve consistency in defining monogenic gene-disease relationships. Here, we outline the precuration process, the lumping and splitting guidelines with examples, and describe the implications for clinical diagnosis, informatics, and care management. Elsevier 2022-05-11 /pmc/articles/PMC9221396/ /pubmed/35754516 http://dx.doi.org/10.1016/j.xgen.2022.100131 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Thaxton, Courtney
Goldstein, Jennifer
DiStefano, Marina
Wallace, Kathleen
Witmer, P. Dane
Haendel, Melissa A.
Hamosh, Ada
Rehm, Heidi L.
Berg, Jonathan S.
Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation
title Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation
title_full Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation
title_fullStr Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation
title_full_unstemmed Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation
title_short Lumping versus splitting: How to approach defining a disease to enable accurate genomic curation
title_sort lumping versus splitting: how to approach defining a disease to enable accurate genomic curation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221396/
https://www.ncbi.nlm.nih.gov/pubmed/35754516
http://dx.doi.org/10.1016/j.xgen.2022.100131
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