Back to Search
Start Over
Mapping OMIM Disease–Related Variations on Protein Domains Reveals an Association Among Variation Type, Pfam Models, and Disease Classes
- Source :
- Frontiers in Molecular Biosciences, Frontiers in Molecular Biosciences, Vol 8 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Human genome resequencing projects provide an unprecedented amount of data about single-nucleotide variations occurring in protein-coding regions and often leading to observable changes in the covalent structure of gene products. For many of these variations, links to Online Mendelian Inheritance in Man (OMIM) genetic diseases are available and are reported in many databases that are collecting human variation data such as Humsavar. However, the current knowledge on the molecular mechanisms that are leading to diseases is, in many cases, still limited. For understanding the complex mechanisms behind disease insurgence, the identification of putative models, when considering the protein structure and chemico-physical features of the variations, can be useful in many contexts, including early diagnosis and prognosis. In this study, we investigate the occurrence and distribution of human disease–related variations in the context of Pfam domains. The aim of this study is the identification and characterization of Pfam domains that are statistically more likely to be associated with disease-related variations. The study takes into consideration 2,513 human protein sequences with 22,763 disease-related variations. We describe patterns of disease-related variation types in biunivocal relation with Pfam domains, which are likely to be possible markers for linking Pfam domains to OMIM diseases. Furthermore, we take advantage of the specific association between disease-related variation types and Pfam domains for clustering diseases according to the Human Disease Ontology, and we establish a relation among variation types, Pfam domains, and disease classes. We find that Pfam models are specific markers of patterns of variation types and that they can serve to bridge genes, diseases, and disease classes. Data are available as Supplementary Material for 1,670 Pfam models, including 22,763 disease-related variations associated to 3,257 OMIM diseases.
- Subjects :
- 0301 basic medicine
QH301-705.5
Protein domain
Context (language use)
Disease
Computational biology
Biology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Biochemistry
03 medical and health sciences
disease-related variation
0302 clinical medicine
OMIM : Online Mendelian Inheritance in Man
protein variations
Molecular Biosciences
disease-related variations
Biology (General)
protein structure
disease variant databases
Molecular Biology
Gene
disease variant database
Original Research
protein domain
food and beverages
Pfam-disease association
030104 developmental biology
Variation (linguistics)
Human genome
Identification (biology)
protein variation
030217 neurology & neurosurgery
variation type
Subjects
Details
- ISSN :
- 2296889X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Molecular Biosciences
- Accession number :
- edsair.doi.dedup.....2d8867225eae2f7cc2f0b50311cae724