Genes Common in Primary Immunodeficiencies and Cancer Display Overrepresentation of Codon CTG and Dominant Role of Selection Pressure in Shaping Codon Usage

Khandia, Rekha; Alqahtani, Taha; Alqahtani, Ali

doi:10.3390/biomedicines9081001

Cited by 20 publications

(19 citation statements)

References 52 publications

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“…The %GC3 content was the most variable compositional parameter and varied between 41.80% and 83.82%. The highest variability in %GC3 and least occurrence of %T in the present study is in concordance with the study of Khandia et al (2021) (36), who reported the same results in the genes common in primary immunodeficiencies and cancer.…”

Section: Discussionsupporting

confidence: 93%

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The G nucleotide guides codon usage bias in genes associated with depression

Khandia

Puranik

Pandey

et al. 2022

Preprint

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Depression or major depressive disorder is a psychiatric disorder affecting mood, behavior, and mental and physical health. Depression runs in families, suggestive of the genetic basis of the disease. Much research is going to understand the molecular basis of depression. In the present work, we tried to envisage the codon usage pattern analysis of genes involved in depression. The investigation revealed that all the genes were highly expressed, and codon usage bias (CUB) is influenced by the length of the gene, nucleotide disproportion, nucleotide compositional constraints, and CAI. The detailed investigation related to the effect of codon composition of CUB revealed that out of 20 compositional constraints, only G nucleotide showed a relationship at overall %G, %G2, %G3 and %GC2 positions. E of composition is further evidenced by the relationship between CUB and nucleotide skew. Neutrality, parity, P2 analysis, suppression of CpG, and TpA dinucleotide and over-representation of TpG dinucleotide followed by under abundance of TpA and CpG encompassing codons and over-representation of CTG and GTG codons all indicated towards the selectional force in shaping codon usage in genes linked to depression. The genes showed a significant positive correlation with each other based on RSCU value indicative of similar codon usage. Based on protein properties, all genes correlated with each other except for the CYP3A4 gene. The association is suggestive of identical protein properties also of genes involved. The analysis helps unveil the compositional features and various forces affecting codon usage of the gene.

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Section: Discussionsupporting

confidence: 93%

“…However, CUB and protein length were positively correlated with GC3 content higher than GC12 content in all the proteins envisaged without any exception. Our results agree with Khandia et al (2021) (36), who found that in all the proteins of size ranging between 150 and 3000 amino acids, GC12 content was lower than GC3 without any exception.…”

Section: Discussionsupporting

confidence: 93%

The G nucleotide guides codon usage bias in genes associated with depression

Khandia

Puranik

Pandey

et al. 2022

Preprint

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“…Even though we did not find a correlation between the CpG and TpG/CpA, TpG dinucleotide-containing codons CTG and GTG were over-represented in 74.46 and 68.08% genes, respectively, while all CpG-containing codons (CGT, GCG, ACG, CCG, and TCG) were under-represented (in 53.19, 72.34, 57.44, 70.21, and 78.72% genes respectively). CTG codon has been over-represented in genes common in primary immunodeficiencies and cancer ( Khandia et al, 2021 ). The same has been depicted in genes associated with brain iron accumulation (Alqahtani et al, 2021) ( Alqahtani et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…The aliphatic index is a suggestive of volume gained by aliphatic side chains. An instability index with an aliphatic index reveals the stability of a protein ( Khandia et al, 2021 ). The isoelectric point is a value where no net electric charge on protein is present, and solubility is minimal ( ScienceDirect Topics, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Codon Usage is Influenced by Compositional Constraints in Genes Associated with Dementia

Alqahtani¹,

Khandia²,

Puranik³

et al. 2022

Front. Genet.

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Dementia is a clinical syndrome characterized by progressive cognitive decline, and the symptoms could be gradual, persistent, and progressive. In the present study, we investigated 47 genes that have been linked to dementia. Compositional, selectional, and mutational forces were seen to be involved. The influence of these two compositional constraints on codon usage bias (CUB) was positive for nucleotide A and negative for GC. Nucleotide A also experienced the highest mutational force, and GC-ending codons were preferred over AT-ending codons. A high bias towards GC-ending codons enhanced the gene expression level, evidenced by the positive association between CAI and GC-ending codons. The unusual behavior of TTG codon showing an inverse relationship with GC-ending codon and negative influence of gene expression, a behavior contrary to all other GC-ending codons, shows operative selectional force. Furthermore, parity analysis, higher translational selection value, preference of GC-ending codons over AT-ending codons, and the association of gene length with gene expression refer to the dominant role of selection pressure with compositional constraint and mutational force shaping codon usage.

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“…Regarding CVID, only 20% of cases are caused by monogenic defects; the remaining 80% derives from polygenic variants and/or from epigenetic alterations [30,31]. Interestingly, a study recently published by Khandia et al considering a panel of 42 genes involved both in PID and cancer highlighted how these genes are under a selection pressure [32]. These cases can be successfully identified crossing whole genome sequencing (WGS) or whole exome sequencing (WES) with RNAseq methods to discover gene-gene interactions and expression dysregulations not detectable by genomic studies only [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience

et al. 2022

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Background: Common variable immunodeficiency (CVID) is a complex, predominantly antibody deficiency usually diagnosed between 20–40 years. Few data about elderly patients are reported in the literature. Our aim was to evaluate the clinical phenotypes of elderly patients with CVID. Method: A retrospective analysis of adult patients with CVID was performed in our Referral Centre, focusing on the main differences between “older” patients (≥ 65 years at the diagnosis) and “younger” patients (< 65 years). Results: The data from 65 younger and 13 older patients followed up for a median period of 8.5 years were available. At diagnosis, recurrent infections represented the only clinical manifestation in 61% and 69% of younger and older patients, respectively. The incidence of autoimmune diseases was higher in elderly patients compared with younger ones (30 vs. 18%, respectively). During the follow-up, the incidence of autoimmune disorders and enteropathy increased in the younger patients whereas neoplasia became the most prevalent complication in the elderly (38%). All patients received a replacement therapy with immunoglobulin, with good compliance. Conclusion: CVID occurrence in elderly patients is rarely described; therefore, the clinical characteristics are not completely known. In our series, neoplasia became the most prevalent complication in the elderly during the follow-up. In elderly patients, 20% SCIg was as safe as in the younger ones, with good compliance. A genetic analysis is important to confirm the diagnosis, identify specific presentations in the different ages, clarify the prognosis and guide the treatment. Future clinical research in this field may potentially help to guide their care.

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Genes Common in Primary Immunodeficiencies and Cancer Display Overrepresentation of Codon CTG and Dominant Role of Selection Pressure in Shaping Codon Usage

Cited by 20 publications

References 52 publications

The G nucleotide guides codon usage bias in genes associated with depression

The G nucleotide guides codon usage bias in genes associated with depression

Codon Usage is Influenced by Compositional Constraints in Genes Associated with Dementia

Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience

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