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Phenogenon: Gene to phenotype associations for rare genetic diseases
- Source :
- PLoS ONE, PLoS ONE, Vol 15, Iss 4, p e0230587 (2020)
- Publication Year :
- 2020
- Publisher :
- Public Library of Science, 2020.
-
Abstract
- As high-throughput sequencing is increasingly applied to the molecular diagnosis of rare Mendelian disorders, a large number of patients with diverse phenotypes have their genetic and phenotypic data pooled together to uncover new gene-phenotype relations. We introduce Phenogenon, a statistical tool that combines, Human Phenotype Ontology (HPO) annotated patient phenotypes, gnomAD allele population frequency, and Combined Annotation Dependent Depletion (CADD) score for variant pathogenicity, in order to jointly predict the mode of inheritance and gene-phenotype associations. We ran Phenogenon on our cohort of 3,290 patients who had undergone whole exome sequencing. Among the top associations, we recapitulated previously known, such as "SRD5A3-Abnormal full-field electroretinogram-recessive" and "GRHL2 -Nail dystrophy-recessive", and discovered one potentially novel, "RRAGA-Abnormality of the skin-dominant". We also developed an interactive web interface available at https://phenogenon.phenopolis.org to visualise and explore the results.
- Subjects :
- 0301 basic medicine
030105 genetics & heredity
Cohort Studies
Gene Frequency
Genotype
Databases, Genetic
Medicine and Health Sciences
Exome sequencing
Visual Impairments
education.field_of_study
Multidisciplinary
Computer-Aided Drug Design
High-Throughput Nucleotide Sequencing
Phenotype
DNA-Binding Proteins
Phenotypes
Medicine
Retinal Disorders
Research Article
Drug Research and Development
Science
Population
Computational biology
Dermatology
Biology
Hair and Nail Diseases
Skin Diseases
03 medical and health sciences
Nail Diseases
Rare Diseases
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
Human Phenotype Ontology
Retinal Dystrophies
Exome Sequencing
Genetics
Humans
Genetic Predisposition to Disease
Allele
education
Allele frequency
Gene
Alleles
Genetic Association Studies
Monomeric GTP-Binding Proteins
Pharmacology
Genetic Diseases, Inborn
Biology and Life Sciences
Computational Biology
Membrane Proteins
Human Genetics
Ophthalmology
030104 developmental biology
Genetic Loci
Drug Design
Genetics of Disease
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 15
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....8e72bb9f8e77f036f5a36aa6f285b887