‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension
Although the invention of right heart catheterisation in the 1950s enabled accurate clinical diagnosis of pulmonary arterial hypertension (PAH), it was not until 2000 when the landmark discovery of the causative role of bone morphogenetic protein receptor type II (<i>BMPR2</i>) mutations...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/11/12/1408 |
| _version_ | 1797546577556930560 |
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| author | Emilia M. Swietlik Matina Prapa Jennifer M. Martin Divya Pandya Kathryn Auckland Nicholas W. Morrell Stefan Gräf |
| author_facet | Emilia M. Swietlik Matina Prapa Jennifer M. Martin Divya Pandya Kathryn Auckland Nicholas W. Morrell Stefan Gräf |
| author_sort | Emilia M. Swietlik |
| collection | DOAJ |
| description | Although the invention of right heart catheterisation in the 1950s enabled accurate clinical diagnosis of pulmonary arterial hypertension (PAH), it was not until 2000 when the landmark discovery of the causative role of bone morphogenetic protein receptor type II (<i>BMPR2</i>) mutations shed new light on the pathogenesis of PAH. Since then several genes have been discovered, which now account for around 25% of cases with the clinical diagnosis of idiopathic PAH. Despite the ongoing efforts, in the majority of patients the cause of the disease remains elusive, a phenomenon often referred to as “missing heritability”. In this review, we discuss research approaches to uncover the genetic architecture of PAH starting with forward phenotyping, which in a research setting should focus on stable intermediate phenotypes, forward and reverse genetics, and finally reverse phenotyping. We then discuss potential sources of “missing heritability” and how functional genomics and multi-omics methods are employed to tackle this problem. |
| first_indexed | 2024-03-10T14:32:46Z |
| format | Article |
| id | doaj.art-296210f1893d40b089d2b306887e3b90 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T14:32:46Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-296210f1893d40b089d2b306887e3b902023-11-20T22:27:50ZengMDPI AGGenes2073-44252020-11-011112140810.3390/genes11121408‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial HypertensionEmilia M. Swietlik0Matina Prapa1Jennifer M. Martin2Divya Pandya3Kathryn Auckland4Nicholas W. Morrell5Stefan Gräf6Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKAlthough the invention of right heart catheterisation in the 1950s enabled accurate clinical diagnosis of pulmonary arterial hypertension (PAH), it was not until 2000 when the landmark discovery of the causative role of bone morphogenetic protein receptor type II (<i>BMPR2</i>) mutations shed new light on the pathogenesis of PAH. Since then several genes have been discovered, which now account for around 25% of cases with the clinical diagnosis of idiopathic PAH. Despite the ongoing efforts, in the majority of patients the cause of the disease remains elusive, a phenomenon often referred to as “missing heritability”. In this review, we discuss research approaches to uncover the genetic architecture of PAH starting with forward phenotyping, which in a research setting should focus on stable intermediate phenotypes, forward and reverse genetics, and finally reverse phenotyping. We then discuss potential sources of “missing heritability” and how functional genomics and multi-omics methods are employed to tackle this problem.https://www.mdpi.com/2073-4425/11/12/1408forward phenotypingforward geneticsreverse geneticsreverse phenotypingpulmonary arterial hypertensionintermediate phenotypes |
| spellingShingle | Emilia M. Swietlik Matina Prapa Jennifer M. Martin Divya Pandya Kathryn Auckland Nicholas W. Morrell Stefan Gräf ‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension Genes forward phenotyping forward genetics reverse genetics reverse phenotyping pulmonary arterial hypertension intermediate phenotypes |
| title | ‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension |
| title_full | ‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension |
| title_fullStr | ‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension |
| title_full_unstemmed | ‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension |
| title_short | ‘There and Back Again’—Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension |
| title_sort | there and back again forward genetics and reverse phenotyping in pulmonary arterial hypertension |
| topic | forward phenotyping forward genetics reverse genetics reverse phenotyping pulmonary arterial hypertension intermediate phenotypes |
| url | https://www.mdpi.com/2073-4425/11/12/1408 |
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