China
Africa
Explore chapters and articles related to this topic
Genetics and exercise: an introduction
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Claude Bouchard, Henning Wackerhage
A typical gene (Figure 3.8) consists of coding sequences termed exons (i.e. exons encode the amino acid sequence of a protein), interrupted by noncoding regions termed introns. Additionally, there are regulatory DNA sequences located upwards and downwards and at times far from the gene whose transcription depends on the regulatory DNA. The number of exons is highly variable, with a range from one (e.g. G-protein-coupled receptor genes, GPCRs, with no introns) to a few hundred exons, such as titin (gene symbol TTN), a gene with 363 exons.
Muscular Dystrophy Diseases
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
Because of the mutational variability in the dystrophin gene, it is essential to use antibodies that correspond to more than one domain; to avoid any false-negative result. Very low levels of dystrophin expression can be detected in some DMD cases, probably from minor transcripts of the gene. It is recently thought to result from exon skipping.
Developmental Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James H. Tonsgard, Nikolas Mata-Machado
A variety of mutations have been demonstrated including missense mutations, nonsense, large deletions, splice-site mutations, point mutations, and small deletions. Missense mutations (which result in a complete protein product) and large deletions (with no protein product) are both associated with milder phenotype. Milder disease is also seen in patients with mutations in exons 9–15. Missense mutations are associated with longer survival than patients with nonsense and frameshift mutations. Patients with mosaicisms may have a milder course and lower risk of having offspring with NF-2. It is anticipated that treatment of NF-2 could ultimately be dictated by the genetic information.
Opioid MOP receptor agonists in late-stage development for the treatment of postoperative pain
Published in Expert Opinion on Pharmacotherapy, 2022
Qiu Qiu, Joshua CJ Chew, Michael G Irwin
Clinicians have long acknowledged both intra- and inter-individual variability in response to MOP receptor agonists. One MOP receptor agonist, e.g. morphine, could give side-effects, while a pharmacodynamically similar alternative, e.g. oxycodone, could be well tolerated. This led to the identification of MOP receptor subtypes. It is only through splice variants or alternative splicing, that it can be understood how multiple MOP receptor subtypes exist but derived from a single gene, OPRM1. Alternative splicing occurs during deoxyribonucleic acid (DNA) translation to messenger ribonucleic acid (mRNA), where exons are combined differently, leading to multiple proteins and receptor subtypes. MOP receptor splice variants have demonstrated differential activity between morphine and morphine-6-glucuronide (M6G) in knock-out mice and it is theorized that this could explain differential side-effect profiles in the two opioids [30].
Associations between OPA1, MFN1, and MFN2 polymorphisms and primary open angle glaucoma in Polish participants of European ancestry
Published in Ophthalmic Genetics, 2022
Piotr Milanowski, Ewa Kosior-Jarecka, Urszula Łukasik, Dominika Wróbel-Dudzińska, Joanna Milanowska, Chiea Chuen Khor, Tin Aung, Janusz Kocki, Tomasz Żarnowski
Despite the number of associations found in this study, we do not know how the presence or lack of particular polymorphisms affect the phenotype of the disease in studied population. There is still no data on association between MFN1 and MFN2 polymorphisms and glaucoma’s clinical features, despite several papers documented such correlation in the case of OPA1 gene. Also unknown are the changes at the molecular level caused by studied polymorphisms that underlie glaucoma’s development. In ADOA, optic nerve degeneration is partly explained by reduced levels of OPA1 protein, an effect of OPA1 haploinsufficiency (29). Likewise, reduced levels of mitochondrial fusion proteins may be responsible for retinal ganglion cells death in glaucoma. Despite only two of the studied polymorphisms being located in exons, defects in mRNA splicing may as well lead to building-in introns into mature mRNA. Other explanations include role of the studied polymorphisms in regulation of other genes’ expression or increasing vulnerability to other glaucoma risk factors. Explanation of mechanisms involved in pathogenesis of this debilitating disease as well as finding associations between studied genes and phenotype of glaucoma in Polish population might be interesting starting points for future studies.
The role of BMP15 and GDF9 in the pathogenesis of primary ovarian insufficiency
Published in Human Fertility, 2021
Meng-na Liu, Kun Zhang, Tian-min Xu
Human BMP15 gene (OMIM:300247) is located at Xp11.22, considered to be a gene duplication product of GDF9 in the TGF-β superfamily, also called GDF9B, associated with the pathogenesis of ovarian dysgenesis2 (OMIM:300510) and POF4 (OMIM:300510). The BMP15 gene comprises of two exons and the major site of expression is in oocytes within the ovary. In mouse and human, the first exon encodes the signal peptide and the first portion of the pro-peptide region, and the second exon encodes the remainder of the pro-peptide region and the entire predicted mature domain (Dube et al., 1998; Persani et al., 2014). As observed for the GDF9 gene (OMIM:601918), it maps on chromosome 5q31.1. Similar to BMP15, GDF9 also consists of two exons and its variation is considered to be causative of POI (de Castro, Cruz, & Leal, 2016). The human promoter part of GDF9 contains NOBOX elements, which act as a transcriptional regulator of the GDF9 and BMP15 genes. Functional studies demonstrated a compromised ability of the mutant NOBOX proteins to bind the NOBOX-binding elements leading to an inhibition of 50% of GDF9 transcriptional activity (Tucker, Grover, Bachelot, Touraine, & Sinclair, 2016). A recent phylogenetic analysis revealed that the GDF9 and BMP15 genes diverged promptly and showed fast evolution compared to other BMPs, only BMP15 was acquiesced to a positive selection in the mammalian clade (Ahmad et al., 2017).