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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-9221396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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