Biology subjects

Rafiq, M. A.

Publications and source records attributed to Rafiq, M. A..

3 recordsLinked to original sources

bioRxiv2025

Mapping the Inter- and Intra-genic Codon Usage Landscape in Homo sapiens

Although the genetic code is degenerate, codon selection is non-random and reflects significant functional constraints. Codon usage bias (CUB) acts as a layer of post-transcriptional regulation, influencing mRNA stability, translation kinetics, and co-translational protein folding. While CUB is well-characterized in unicellular organisms, its regulatory scope and functional consequences in humans remain complex and less defined. Our study offers a comprehensive evaluation of human codon usage. We report that genes exhibiting the strongest codon bias are enriched in high-stoichiometry biological processes, such as skin development and oxygen/carbon dioxide transport, and harbor significantly fewer synonymous variants than expected ({rho} = -0.24, p < 2.2 x 10-16). Furthermore, we find that codon optimization is spatially regulated: it is significantly more pronounced in structured protein domains compared to intrinsically disordered regions (IDRs) (Cliffs {Delta}= 0.26, p < 2.2 x 10-16). Consistent with translational selection, the most frequently used codons are supported by higher tRNA gene copy numbers ({rho} = 0.49, p < 6.4 x 10-4). Finally, by correcting for GC3 content, we reveal that the apparent correlation between ENC and adaptation indices (CAI/tAI) vanishes, allowing us to disentangle mutational pressure from translational selection. Collectively, our findings position codon usage bias as a central, evolutionarily conserved regulator of translation and protein folding in humans. Our results provide a comprehensive and integrated view of intergenic and intragenic codon usage bias in humans, reinforcing the biological relevance of synonymous codon choice in shaping translational dynamics and protein biogenesis. This provides a refined framework for interpreting synonymous variation and guiding functional genomics.

genomics↗

bioRxiv2019

Animal model and therapeutic prospects for left ventricular hypertrophy and associated renal complication

Cardiac and renal dysfunction often co-occur and considerably worsen the prognosis leading to difficulty in therapy in left ventricular hypertrophy (LVH). The aim of this study was to elucidate changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and gasotransmitter, H2S (hydrogen sulphide) and NO (nitric oxide) and combined (H2S+NO), treatment of rat myocardium and renal tissues. LVH rat models were generated and were treated with H2S and NO. Relative gene expression was quantified. Heart and renal physical indices were significantly modified under individual as well as combined H2S+NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNF and IGF1, mRNAs to be significantly increased (P<0.05) in myocardia and kidneys of LVH rats, while individual and combined H2S+NO treatment reduced gene expression to normal/near to normal values. The cardiac remodeling genes MYH7, TGF{beta}, SMAD4 and BRG1 expression were significantly up-regulated (P<0.05) in the myocardia of LVH and combined H2S+NO treatment, which recovered the normal/near to normal expression more effectively as compared to individual treatments. Interestingly, individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was significantly up-regulated in LVH rats (P<0.05). The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment in LVH rat model indicates important therapeutic potential of combined treatment with H2S+NO gasotransmitters in hypertension and cardiac hypertrophy associated with renal complications.

pharmacology and toxicology↗

bioRxiv2016

Mapping Autosomal Recessive Intellectual Disability: Combined Microarray and Exome Sequencing Identifies 26 Novel Candidate Genes in 192 Consanguineous Families

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7, and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

genetics↗