Genetics and exercise: an introduction
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
With 3.2 billion pairs of nucleotides in the haploid human genome, about 20 million genes could be encoded. However, there are about 1,000 times fewer protein-coding genes than this estimate. But there are many more proteins than the 20,465 protein-coding sequences currently recognized in the human genome. The higher number of encoded proteins, for which the absolute number is still a matter of debate, is explained mainly by DNA-coding sequences producing more than one mRNA transcript, called a transcript variant. The disparity between the number of genes and gene transcripts results most frequently from alternative promoters and alternative splicing. As described above, splicing is the process by which introns are removed and exons sequences are fused together into an mRNA. Alternative splicing refers to a situation in which a single gene produces multiple messenger RNAs through different combinations of exons (Figure 3.9). Approximately 75% of the human genes with multiple exons have alternative splice sites. Alternative splicing may cause either inclusion or exclusion of one or several exons.
RNA-seq Analysis
Altuna Akalin in Computational Genomics with R, 2020
RNA-seq generates valuable data that contains information not only at the gene level but also at the level of exons and transcripts. Moreover, the kind of information that we can extract from RNA-seq is not limited to expression quantification. It is possible to detect alternative splicing events such as novel isoforms (Trapnell et al., 2010), and differential usage of exons (Anders et al., 2012). It is also possible to observe sequence variants (substitutions, insertions, deletions, RNA-editing) that may change the translated protein product (McKenna et al., 2010). In the context of cancer genomes, gene-fusion events can be detected with RNA-seq (McPherson et al., 2011). Finally, for the purposes of gene prediction or improving existing gene predictions, RNA-seq is a valuable method (Stanke and Morgenstern, 2005). In order to learn more about how to implement these, it is recommended that you go through the tutorials of the cited tools.
The Syndromes of Reduced Responsiveness to Thyroid Hormone
Geraldo Medeiros-Neto, John Bruton Stanbury in Inherited Disorders of the Thyroid System, 2019
Two thyroid hormone receptor genes (TR-α and TR-β) are encoded, respectively, on chromosomes 17 and 3 (17ql 1.2-21 and 3p.22-24). These have strong structural similarity. Two proteins derive from each of these genes, and are called, respectively, TR-ocl and TR-CC2 and TR-βl and TB-β2 (Table 4). They are highly homologous and are widely distributed, but distribution varies among different tissues, and even within cells in the same tissue. For an example, TR-β2 is expressed only in the pituitary and in localized zones of the central nervous system. Isoforms of each of these proteins are also formed by alternative splicing. The TR-oc2 protein does not bind hormone because of an alternation in its terminal carboxyl sequence and accordingly does not function as a hormone receptor, but it does bind to the thyroid hormone response elements (TRE). The two receptor genes and their products vary from one tissue to the next and may differ at different stages of development.
Association analysis of the surfactant protein-C gene to childhood asthma
Published in Journal of Asthma, 2022
Malek Nefzi, Imen Wahabi, Sondess Hadj Fredj, Rym Othmani, Rym Dabboubi, Khedija Boussetta, Pascale Fanen, Taieb Messaoud
We have also identified the c(0).43–7 G > A (rs79440568) variation in the skipping region of exon 2 that had been firstly described by Lawson et al. to be associated with idiopathic pulmonary fibrosis (34) and also by Tarocco et al. for its association with a neonatal respiratory distress case with an African ethnicity (35). A splicing defect has been suggested to be induced by the c(0).435–8 C > G variation that may contribute to a new acceptor site of the cDNA. Alternative splicing contributes significantly to the complexity of the human genome suggesting that 60% of genes have alternative splice forms (36). The concept of splicing regulation by ‘‘enhancers’’ and ‘‘silencers’’, stipulates that sequence elements within exons or introns can promote or inhibit splicing at nearby splice sites (26). Thus, an intronic or exonic mutation could be postulated to affect transcription and protein translation.
The role of systemic corticosteroids in severe asthma and new evidence in their management and tapering
Published in Expert Review of Clinical Immunology, 2021
Francesco Menzella, Giulia Ghidoni, Matteo Fontana, Silvia Capobelli, Francesco Livrieri, Claudia Castagnetti, Nicola Facciolongo
The glucocorticoid receptor (GR) is part of the nuclear receptor group, a family of ligand-dependent transcription factors. Its gene, NR3C1, is located on chromosome 5q31, and it has an extension of about 150 kB. In addition to the variants for the first exon, alternative splicing also occurs at the 3ʹ-end, where two variants of exon 9 can be used leading to GRα and GRβ, respectively [14]. Alongside these splice variants, the presence of alternative start codons gives rise to a series of translational isoforms, which can be differentially expressed in various tissues [15]. When the ligand is not present, the receptor is found in the cytoplasm as a multiprotein complex associated with various chaperone proteins (HSP90, HSP23, FKBP51 and 52). After binding to the ligand, the complex dissociates and the bound receptor translocates to the nucleus. In the nucleus, the receptor can interact with specific DNA sequences, with glucocorticoid response elements (GRE), or with other transcription factors, and ultimately it can regulate the transcription of target genes [15]. The gene coding for the GR consists of nine exons. Literature data showed that resistance to glucocorticosteroids is due to the ER22/23EK polymorphism. On the contrary, the BclI polymorphism significantly influences the splicing process of the alternative NR3C1 gene and consequently increases the sensitivity to glucocorticoids (GC). Other evidence confirms that the Tth111I polymorphism of the NR3C1 gene plays an important role in the pathogenesis of both allergic and non-allergic asthma [16].
SPLICELECT™: an adaptable cell surface display technology based on alternative splicing allowing the qualitative and quantitative prediction of secreted product at a single-cell level
Published in mAbs, 2020
Christel Aebischer-Gumy, Pierre Moretti, Romain Ollier, Christelle Ries Fecourt, François Rousseau, Martin Bertschinger
Interestingly, the human immune system provides an additional and elegant way to link cell surface display and secretion. B cells are the antibody producers in the human immune system. Each B cell expresses a single antibody specifically binding a single antigen. In resting B cells (memory cells), the antibody is predominantly membrane-bound. Upon recognition of its antigen, a B cell will proliferate into plasma cells expressing a huge amount of secreted antibody.44 The only difference between the two antibody isoforms is a C-terminal extension of the membrane-bound version with a transmembrane region.45 The controlled transition between the two isoforms of antibody (membrane-bound and secreted) is achieved by alternative splicing.45,46 Splicing describes the precise excision of the introns of the mRNA, accomplished by a protein complex called spliceosome that is able to recognize consensus sequences: the 5ʹ splice donor (5ʹ SD) and 3ʹ splice acceptor (3’SA) sites at the intron/exon borders and the branch point and the poly pyrimidines (poly(Y)) tract in the intron. The efficiency of the splicing depends largely on the different consensus sequences, but also on so-called splicing enhancer and repressor sequences present in both introns and exons. Alternative splicing describes the mechanisms by which a single pre-mRNA is matured into different mRNA, a process that is usually highly regulated by interaction of many different factors.47–58
Related Knowledge Centers
- Eukaryote
- Exon
- Exon Skipping
- Gene Expression
- Genetic Code
- Protein
- Rna Splicing
- Messenger Rna
- Rna Splicing
- Gene
- Messenger Rna
- Translation