Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes
Rare genetic disorders, while individually rare, are collectively common. They represent some of the most severe disorders affecting patients worldwide with significant morbidity and mortality. Over the last decade, advances in genomic methods have significantly uplifted diagnostic rates for patient...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-06-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.674295/full |
| _version_ | 1818601047538532352 |
|---|---|
| author | Eleanor G. Seaby Eleanor G. Seaby Eleanor G. Seaby Eleanor G. Seaby Heidi L. Rehm Heidi L. Rehm Anne O’Donnell-Luria Anne O’Donnell-Luria Anne O’Donnell-Luria Anne O’Donnell-Luria |
| author_facet | Eleanor G. Seaby Eleanor G. Seaby Eleanor G. Seaby Eleanor G. Seaby Heidi L. Rehm Heidi L. Rehm Anne O’Donnell-Luria Anne O’Donnell-Luria Anne O’Donnell-Luria Anne O’Donnell-Luria |
| author_sort | Eleanor G. Seaby |
| collection | DOAJ |
| description | Rare genetic disorders, while individually rare, are collectively common. They represent some of the most severe disorders affecting patients worldwide with significant morbidity and mortality. Over the last decade, advances in genomic methods have significantly uplifted diagnostic rates for patients and facilitated novel and targeted therapies. However, many patients with rare genetic disorders still remain undiagnosed as the genetic etiology of only a proportion of Mendelian conditions has been discovered to date. This article explores existing strategies to identify novel Mendelian genes and how these discoveries impact clinical care and therapeutics. We discuss the importance of data sharing, phenotype-driven approaches, patient-led approaches, utilization of large-scale genomic sequencing projects, constraint-based methods, integration of multi-omics data, and gene-to-patient methods. We further consider the health economic advantages of novel gene discovery and speculate on potential future methods for improved clinical outcomes. |
| first_indexed | 2024-12-16T12:45:10Z |
| format | Article |
| id | doaj.art-1f94c5ca62e1406f9efa011c919c0a61 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-16T12:45:10Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-1f94c5ca62e1406f9efa011c919c0a612022-12-21T22:31:18ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-06-011210.3389/fgene.2021.674295674295Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical OutcomesEleanor G. Seaby0Eleanor G. Seaby1Eleanor G. Seaby2Eleanor G. Seaby3Heidi L. Rehm4Heidi L. Rehm5Anne O’Donnell-Luria6Anne O’Donnell-Luria7Anne O’Donnell-Luria8Anne O’Donnell-Luria9Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United StatesGenomic Informatics Group, University Hospital Southampton, Southampton, United KingdomCenter for Genomic Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United StatesDivision of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, United StatesProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United StatesCenter for Genomic Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United StatesProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United StatesCenter for Genomic Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United StatesDivision of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, United StatesManton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA, United StatesRare genetic disorders, while individually rare, are collectively common. They represent some of the most severe disorders affecting patients worldwide with significant morbidity and mortality. Over the last decade, advances in genomic methods have significantly uplifted diagnostic rates for patients and facilitated novel and targeted therapies. However, many patients with rare genetic disorders still remain undiagnosed as the genetic etiology of only a proportion of Mendelian conditions has been discovered to date. This article explores existing strategies to identify novel Mendelian genes and how these discoveries impact clinical care and therapeutics. We discuss the importance of data sharing, phenotype-driven approaches, patient-led approaches, utilization of large-scale genomic sequencing projects, constraint-based methods, integration of multi-omics data, and gene-to-patient methods. We further consider the health economic advantages of novel gene discovery and speculate on potential future methods for improved clinical outcomes.https://www.frontiersin.org/articles/10.3389/fgene.2021.674295/fullMendeliannovel gene discoverydisease–gene relationshipsrare genetic disordersgenomicsrare disease |
| spellingShingle | Eleanor G. Seaby Eleanor G. Seaby Eleanor G. Seaby Eleanor G. Seaby Heidi L. Rehm Heidi L. Rehm Anne O’Donnell-Luria Anne O’Donnell-Luria Anne O’Donnell-Luria Anne O’Donnell-Luria Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes Frontiers in Genetics Mendelian novel gene discovery disease–gene relationships rare genetic disorders genomics rare disease |
| title | Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes |
| title_full | Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes |
| title_fullStr | Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes |
| title_full_unstemmed | Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes |
| title_short | Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes |
| title_sort | strategies to uplift novel mendelian gene discovery for improved clinical outcomes |
| topic | Mendelian novel gene discovery disease–gene relationships rare genetic disorders genomics rare disease |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.674295/full |
| work_keys_str_mv | AT eleanorgseaby strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT eleanorgseaby strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT eleanorgseaby strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT eleanorgseaby strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT heidilrehm strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT heidilrehm strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT anneodonnellluria strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT anneodonnellluria strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT anneodonnellluria strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes AT anneodonnellluria strategiestoupliftnovelmendeliangenediscoveryforimprovedclinicaloutcomes |