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| Format: | Artículo científico |
| Langue: | en |
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Human genetics
2024
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| Accès en ligne: | https://pubmed.ncbi.nlm.nih.gov/39488654/ |
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| _version_ | 1868266284965167105 |
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| author | Lopes-Marques, Mónica Peixoto, M João Cooper, David N Prata, M João Azevedo, Luísa Castro, L Filipe C |
| author_facet | Lopes-Marques, Mónica Peixoto, M João Cooper, David N Prata, M João Azevedo, Luísa Castro, L Filipe C Lopes-Marques, Mónica Peixoto, M João Cooper, David N Prata, M João Azevedo, Luísa Castro, L Filipe C |
| collection | PubMed - marine biology |
| contents | Polymorphic pseudogenes in the human genome - a comprehensive assessment. Lopes-Marques, Mónica Peixoto, M João Cooper, David N Prata, M João Azevedo, Luísa Castro, L Filipe C Humans Pseudogenes Genome, Human Polymorphism, Genetic Alleles Loss of Function Mutation Over the past decade, variations of the coding portion of the human genome have become increasingly evident. In this study, we focus on polymorphic pseudogenes, a unique and relatively unexplored type of pseudogene whose inactivating mutations have not yet been fixed in the human genome at the global population level. Thus, polymorphic pseudogenes are characterized by the presence in the population of both coding alleles and non-coding alleles originating from Loss-of-Function (LoF) mutations. These alleles can be found both in heterozygosity and in homozygosity in different human populations and thus represent pseudogenes that have not yet been fixed in the population. A methodical cross-population analysis of 232 polymorphic pseudogenes, including 35 new examples, reveals that human olfactory signalling, drug metabolism and immunity are among the systems most impacted by the variable presence of LoF variants at high frequencies. Within this dataset, a total of 179 genes presented polymorphic LoF variants in all analysed populations. Transcriptome and proteome analysis confirmed that although these genes may harbour LoF alleles, when the coding allele is present, the gene remains active and can play a functional role in various metabolic pathways, including drug/xenobiotic metabolism and immunity. The observation that many polymorphic pseudogenes are members of multigene families argues that genetic redundancy may play a key role in compensating for the inactivation of one paralogue. The distribution, expression and integration of cellular/biological networks in relation to human polymorphic pseudogenes, provide novel insights into the architecture of the human genome and the dynamics of gene gain and loss with likely functional impact. |
| format | Artículo científico |
| id | pubmed_39488654 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Human genetics |
| record_format | pubmed |
| spellingShingle | Polymorphic pseudogenes in the human genome - a comprehensive assessment. Lopes-Marques, Mónica Peixoto, M João Cooper, David N Prata, M João Azevedo, Luísa Castro, L Filipe C Humans Pseudogenes Genome, Human Polymorphism, Genetic Alleles Loss of Function Mutation Polymorphic pseudogenes in the human genome - a comprehensive assessment. Lopes-Marques, Mónica Peixoto, M João Cooper, David N Prata, M João Azevedo, Luísa Castro, L Filipe C Humans Pseudogenes Genome, Human Polymorphism, Genetic Alleles Loss of Function Mutation Over the past decade, variations of the coding portion of the human genome have become increasingly evident. In this study, we focus on polymorphic pseudogenes, a unique and relatively unexplored type of pseudogene whose inactivating mutations have not yet been fixed in the human genome at the global population level. Thus, polymorphic pseudogenes are characterized by the presence in the population of both coding alleles and non-coding alleles originating from Loss-of-Function (LoF) mutations. These alleles can be found both in heterozygosity and in homozygosity in different human populations and thus represent pseudogenes that have not yet been fixed in the population. A methodical cross-population analysis of 232 polymorphic pseudogenes, including 35 new examples, reveals that human olfactory signalling, drug metabolism and immunity are among the systems most impacted by the variable presence of LoF variants at high frequencies. Within this dataset, a total of 179 genes presented polymorphic LoF variants in all analysed populations. Transcriptome and proteome analysis confirmed that although these genes may harbour LoF alleles, when the coding allele is present, the gene remains active and can play a functional role in various metabolic pathways, including drug/xenobiotic metabolism and immunity. The observation that many polymorphic pseudogenes are members of multigene families argues that genetic redundancy may play a key role in compensating for the inactivation of one paralogue. The distribution, expression and integration of cellular/biological networks in relation to human polymorphic pseudogenes, provide novel insights into the architecture of the human genome and the dynamics of gene gain and loss with likely functional impact. |
| title | Polymorphic pseudogenes in the human genome - a comprehensive assessment. |
| topic | Humans Pseudogenes Genome, Human Polymorphism, Genetic Alleles Loss of Function Mutation |
| url | https://pubmed.ncbi.nlm.nih.gov/39488654/ |