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Biochemistry. Biokhimiia Nov 2018Pseudogene is a gene copy that has lost its original function. For a long time, pseudogenes have been considered as "junk DNA" that inevitably arises as a result of... (Review)
Review
Pseudogene is a gene copy that has lost its original function. For a long time, pseudogenes have been considered as "junk DNA" that inevitably arises as a result of ongoing evolutionary process. However, experimental data obtained during recent years indicate this understanding of the nature of pseudogenes is not entirely correct, and many pseudogenes perform important genetic functions. In the review, we have addressed classification of pseudogenes, methods of their detection in the genome, and the problem of their evolutionary conservatism and prevalence among species belonging to different taxonomic groups in the light of modern data. The mechanisms of gene expression regulation by pseudogenes and the role of pseudogenes in pathogenesis of various human diseases are discussed.
Topics: Animals; Evolution, Molecular; Genome, Human; Humans; Pseudogenes
PubMed: 30482145
DOI: 10.1134/S0006297918110044 -
Genome Medicine May 2017The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome... (Review)
Review
The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome sequencing. However, in a considerable number of patients, the genetic basis remains unclear. As clinicians begin to consider whole-genome sequencing, an understanding of the processes and tools involved and the factors to consider in the annotation of the structure and function of genomic elements that might influence variant identification is crucial. Here, we discuss and illustrate the strengths and weaknesses of approaches for the annotation and classification of important elements of protein-coding genes, other genomic elements such as pseudogenes and the non-coding genome, comparative-genomic approaches for inferring gene function, and new technologies for aiding genome annotation, as a practical guide for clinicians when considering pathogenic sequence variation. Complete and accurate annotation of structure and function of genome features has the potential to reduce both false-negative (from missing annotation) and false-positive (from incorrect annotation) errors in causal variant identification in exome and genome sequences. Re-analysis of unsolved cases will be necessary as newer technology improves genome annotation, potentially improving the rate of diagnosis.
Topics: Diagnostic Techniques and Procedures; Genetic Variation; Humans; Molecular Sequence Annotation; Pseudogenes; Sequence Analysis, DNA
PubMed: 28558813
DOI: 10.1186/s13073-017-0441-1 -
Methods in Molecular Biology (Clifton,... 2021Long intergenic noncoding RNAs (lincRNAs) are known to be tissue specifically expressed and able to regulate functional protein-coding genes: some can even act as...
Long intergenic noncoding RNAs (lincRNAs) are known to be tissue specifically expressed and able to regulate functional protein-coding genes: some can even act as competing endogenous RNAs (ceRNAs), because microRNAs can bind to them instead of the corresponding mRNA binding sites. Some lincRNAs contain remnants of protein-coding sequences and it has been hypothesized that they might arise after a pseudogenization processes. However, a major limitation in the study of such phenomenon is the lack of proper computational tools designed to align/analyze protein-coding sequences and noncoding sequences. To overcome this limitation, we published a method that finds the remnants of protein-coding sequences within the sequence of lincRNAs, as well as the corresponding sequences in parental proteins. This method, together with the visualization platform for tracing frameshifts and single point mutations within this type of sequences, are described here.
Topics: Amino Acid Sequence; Computational Biology; MicroRNAs; Open Reading Frames; Pseudogenes; RNA, Long Noncoding; RNA, Messenger; Sequence Alignment; Sequence Analysis, RNA
PubMed: 34165708
DOI: 10.1007/978-1-0716-1503-4_4 -
Medicine Feb 2016Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage and is largely attributed to genetic risk factors. Single nucleotide... (Meta-Analysis)
Meta-Analysis Review
Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage and is largely attributed to genetic risk factors. Single nucleotide polymorphisms (SNPs) are common DNA variants that have shown promising and efficiency, compared with positional cloning, to map candidate genes of complex diseases, including OA. In this study, we aim to provide an overview of multiple SNPs from a number of genes that have recently been linked to OA susceptibility. We also performed a comprehensive meta-analysis to evaluate the association of SNP rs7639618 of double von Willebrand factor A domains (DVWA) gene with OA susceptibility. A systematic search of studies on the association of SNPs with susceptibility to OA was conducted in PubMed and Google scholar. Studies subjected to meta-analysis include human and case-control studies that met the Hardy-Weinberg equilibrium model and provide sufficient data to calculate an odds ratio (OR). A total of 9500 OA cases and 9365 controls in 7 case-control studies relating to SNP rs7639618 were included in this study and the ORs with 95% confidence intervals (CIs) were calculated. Over 50 SNPs from different genes have been shown to be associated with either hip (23), or knee (20), or both (13) OA. The ORs of these SNPs for OA and the subtypes are not consistent. As to SNP rs7639618 of DVWA, increased knee OA risk was observed in all genetic models analyzed. Specifically, people from Asian with G-allele showed significantly increased risk of knee OA (A versus G: OR = 1.28, 95% CI 1.13-1.46; AA versus GG: OR = 1.60, 95% CI 1.25-2.05; GA versus GG: OR = 1.31, 95% CI 1.18-1.44; AA versus GA+GG: OR = 1.34, 95% CI 1.12-1.61; AA+GA versus GG: OR = 1.40, 95% CI 1.19-1.64), but not in Caucasians or with hip OA. Our results suggest that multiple SNPs play different roles in the pathogenesis of OA and its subtypes; SNP rs7639618 of DVWA gene is associated with a significantly increased risk of knee OA in Asians. Given the limited sample size, further studies are needed to evaluate this observation.
Topics: Collagen Type VI; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Odds Ratio; Osteoarthritis; Polymorphism, Single Nucleotide; Pseudogenes
PubMed: 26886631
DOI: 10.1097/MD.0000000000002811 -
Nature Genetics Aug 2020Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in healthcare, the need for a consistent...
Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in healthcare, the need for a consistent language for human genes becomes ever more vital. Here we present the current HUGO Gene Nomenclature Committee (HGNC) guidelines for naming not only protein-coding but also RNA genes and pseudogenes, and outline the changes in approach and ethos that have resulted from the discoveries of the last few decades.
Topics: Genes; Human Genetics; Humans; Pseudogenes; RNA
PubMed: 32747822
DOI: 10.1038/s41588-020-0669-3 -
Scientific Reports Oct 2022Colorectal cancer (CRC) is one of the most common and malignant carcinomas. Many long noncoding RNAs (lncRNAs) have been reported to play important roles in the...
Colorectal cancer (CRC) is one of the most common and malignant carcinomas. Many long noncoding RNAs (lncRNAs) have been reported to play important roles in the tumorigenesis of CRC by influencing the expression of some mRNAs via competing endogenous RNA (ceRNA) networks and interacting with miRNAs. Pseudogene is one kind of lncRNA and can act as RNA sponges for miRNAs and regulate gene expression via ceRNA networks. However, there are few studies about pseudogenes in CRC. In this study, 31 differentially expressed (DE) pseudogenes, 17 DE miRNAs and 152 DE mRNAs were identified by analyzing the expression profiles of colon adenocarcinoma obtained from The Cancer Genome Atlas. A ceRNA network was constructed based on these RNAs. Kaplan-Meier analysis showed that 7 pseudogenes, 4 miRNAs and 30 mRNAs were significantly associated with overall survival. Then multivariate Cox regression analysis of the ceRNA-related DE pseudogenes was performed and a 5-pseudogene signature with the greatest prognostic value for CRC was identified. Moreover, the results were validated by the Gene Expression Omnibus database, and quantitative real-time PCR in 113 pairs of CRC tissues and colon cancer cell lines. This study provides a pseudogene-associated ceRNA network, 7 prognostic pseudogene biomarkers, and a 5-pseudogene prognostic risk signature that may be useful for predicting the survival of CRC patients.
Topics: Humans; RNA, Long Noncoding; Prognosis; Pseudogenes; Gene Regulatory Networks; Gene Expression Regulation, Neoplastic; Adenocarcinoma; Colonic Neoplasms; MicroRNAs; RNA, Messenger; Biomarkers
PubMed: 36272991
DOI: 10.1038/s41598-022-22768-y -
International Journal of Oncology Mar 2024Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain...
Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non‑coding RNAs, reverse transcription‑quantitative PCR, fluorescence hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for studies. and studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor‑promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR‑6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR‑6072/UBD network may serve as a potential therapeutic strategy for glioma patients.
Topics: Animals; Humans; Mice; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioma; In Situ Hybridization, Fluorescence; MicroRNAs; Pseudogenes; RNA, Long Noncoding
PubMed: 38275102
DOI: 10.3892/ijo.2024.5617 -
Amino Acids Jul 2017Bitter taste receptors (Tas2rs) play important roles in mammalian defense mechanisms by helping animals detect and avoid toxins in food. Although Tas2r genes have been... (Review)
Review
Bitter taste receptors (Tas2rs) play important roles in mammalian defense mechanisms by helping animals detect and avoid toxins in food. Although Tas2r genes have been widely studied in several mammals, minimal research has been performed in canids. To analyze the genetic basis of Tas2r genes in canids, we first identified Tas2r genes in the wolf, maned wolf, red fox, corsac fox, Tibetan fox, fennec fox, dhole and African hunting dog. A total of 183 Tas2r genes, consisting of 118 intact genes, 6 partial genes and 59 pseudogenes, were detected. Differences in the pseudogenes were observed among nine canid species. For example, Tas2r4 was a pseudogene in the dog but might play a functional role in other canid species. The Tas2r42 and Tas2r10 genes were pseudogenes in the maned wolf and dhole, respectively, and the Tas2r5 and Tas2r34 genes were pseudogenes in the African hunting dog; however, these genes were intact genes in other canid species. The differences in Tas2r pseudogenes among canids might suggest that the loss of intact Tas2r genes in canid species is species-dependent. We further compared the 183 Tas2r genes identified in this study with Tas2r genes from ten additional carnivorous species to evaluate the potential influence of diet on the evolution of the Tas2r gene repertoire. Phylogenetic analysis revealed that most of the Tas2r genes from the 18 species intermingled across the tree, suggesting that Tas2r genes are conserved among carnivores. Within canids, we found that some Tas2r genes corresponded to the traditional taxonomic groupings, while some did not. PIC analysis showed that the number of Tas2r genes in carnivores exhibited no positive correlation with diet composition, which might be due to the limited number of carnivores included in our study.
Topics: Animals; Canidae; Phylogeny; Pseudogenes; Receptors, G-Protein-Coupled; Species Specificity
PubMed: 28417226
DOI: 10.1007/s00726-017-2422-5 -
BMC Plant Biology Mar 2023Blueberries (Vaccinium section Cyanococcus) are an economically important fruit crop in the United States. Understanding genetic structure and relationships in...
BACKGROUND
Blueberries (Vaccinium section Cyanococcus) are an economically important fruit crop in the United States. Understanding genetic structure and relationships in blueberries is essential to advance the genetic improvement of horticulturally important traits. In the present study, we investigated the genomic and evolutionary relationships in 195 blueberry accessions from five species (comprising 33 V. corymbosum, 14 V. boreale, 81 V. darrowii, 29 V. myrsinites, and 38 V. tenellum) using single nucleotide polymorphisms (SNPs) mined from genotyping-by-sequencing (GBS) data.
RESULTS
GBS generated ~ 751 million raw reads, of which 79.7% were mapped to the reference genome V. corymbosum cv. Draper v1.0. After filtering (read depth > 3, minor allele frequency > 0.05, and call rate > 0.9), 60,518 SNPs were identified and used in further analyses. The 195 blueberry accessions formed three major clusters on the principal component (PC) analysis plot, in which the first two PCs accounted for 29.2% of the total genetic variance. Nucleotide diversity (π) was highest for V. tenellum and V. boreale (0.023 each), and lowest for V. darrowii (0.012). Using TreeMix analysis, we identified four migration events and deciphered gene flow among the selected species. In addition, we detected a strong V. boreale lineage in cultivated blueberry species. Pairwise SweeD analysis identified a wide sweep (encompassing 32 genes) as a strong signature of domestication on the scaffold VaccDscaff 12. From this region, five genes encoded topoisomerases, six genes encoded CAP-gly domain linker (which regulates the dynamics of the microtubule cytoskeleton), and three genes coded for GSL8 (involved in the synthesis of the cell wall component callose). One of the genes, augustus_masked-VaccDscaff12-processed-gene-172.10, is a homolog of Arabidopsis AT2G25010 and encodes the protein MAINTENANCE OF MERISTEMS-like involved in root and shoot growth. Additional genomic stratification by admixture analysis identified genetic lineages and species boundaries in blueberry accessions. The results from this study indicate that V. boreale is a genetically distant outgroup, while V. darrowii, V. myrsinites, and V. tenellum are closely related.
CONCLUSION
Our study provides new insights into the evolution and genetic architecture of cultivated blueberries.
Topics: Blueberry Plants; Genomics; Pseudogenes; Arabidopsis; Cell Wall
PubMed: 36872311
DOI: 10.1186/s12870-023-04124-y -
Biomedicine & Pharmacotherapy =... Oct 2016Lung cancer is one of the most common mortal cancer types both for men and women. Several different biomarkers have been analyzed to reveal lung cancer prognosis... (Review)
Review
Lung cancer is one of the most common mortal cancer types both for men and women. Several different biomarkers have been analyzed to reveal lung cancer prognosis pathways for developing efficient therapeutics and diagnostic agents. microRNAs (miRNAs) and pseudogenes are critical biomarkers in lung cancer and alteration of their expression levels has been identified in each step of lung cancer tumorigenesis. miRNAs and pseudogenes are crucial gene regulators in normal cells as well as in lung cancer cells, and they have both oncogenic and tumor-suppressive roles in lung cancer tumorigenesis. In this study, we have determined the relationship between lung cancer related oncogenes and miRNAs along with pseudogenes in lung cancer, and the results indicate their potential as biological markers for diagnostic and therapeutic purposes.
Topics: Biomarkers, Tumor; Carcinogenesis; Female; Humans; Lung Neoplasms; Male; MicroRNAs; Oncogenes; Pseudogenes
PubMed: 27551766
DOI: 10.1016/j.biopha.2016.08.043