China
Africa
Explore chapters and articles related to this topic
The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
Point mutations are the simplest form of DNA alteration (Figure 2.9). In this case, a single nucleotide of the DNA sequence is affected. If a mutation affects the protein-coding sequence of a gene, it is termed silent if it does not alter the encoded amino acid. A missense mutation occurs when DNA alterations encode a different amino acid. Sometimes, the effects are more drastic; a mutation which introduces an early stop codon (nonsense mutation) will terminate protein translation and full-length protein will not be produced. Similarly, gain or loss of one or two nucleotides will alter the subsequent reading frame of the protein and the remainder of the correct sequence will be lost. Pathogenic mutations may also occur outside a protein-coding sequence; alterations to promoter regions or splice sites can have profound effects on gene expression.
Cancer Informatics
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
In our last analysis, we look at mutations in the genes. The mutation data is stored in MAF files (Mutation Annotation Format) which are downloaded in like manner to the expression data. The Bioconductor package maftools is used to analyse the data. The functions getGeneSummary() and getSampleSummary() summarise the mutations. There are five types of mutation recorded: Missense mutation: a change in a base pair that leads to a different amino acid being used in the resulting protein.Nonsense mutation: a change in a base pair that leads to a premature stop codon.Nonstop mutation: a change in a base pair in a stop codon leading to further inappropriate translation.Splice site: an alteration at the boundary af an exon and an intron.Translation start site: an alteration of the start site of translation of a gene.
What causes Rett Syndrome
Published in Rosa Angela Fabio, Tindara Caprì, Gabriella Martino, Understanding Rett Syndrome, 2019
Rosa Angela Fabio, Tindara Caprì, Gabriella Martino
A study by Fabio and colleagues (2014) evaluated a cohort of 114 RTT patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype–phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as one producing mild impairment, was associated with a moderate phenotype in which behavioral characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference generally concerned the motorfunctional and autonomy skills of the patients, affecting the management of everyday activities.
Dominantly Inherited β-Thalassemia Caused by a Single Nucleotide Deletion in Exon 3 of the β-Globin Gene: Hb Xiangyang (HBB: c.393delT)
Published in Hemoglobin, 2022
Xiao-Mei Lin, Fan Jiang, Jian Li, Dong-Zhi Li
Currently, more than 40 varieties of dominantly inherited β-thal alleles have been described [3–12]. They have been classified as four molecular groups: (a) missense mutations, (b) deletions or insertions of one intact codon, (c) single base substitutions leading to premature termination and (d) frameshifts resulting in elongated β chains. Of the known dominantly inherited β-thal mutations, the majority are located in exon 3 of the β-globin gene, producing unstable β-globin chains. The pathological mechanisms have not been fully understood. One hypothesis explains why most mutations involving exons 1 and 2 are mild, while those involving exon 3 are more severe [6]. The mRNAs of mutations producing truncated β chains up to 72 residues in length are not transported to the cytoplasm, and thus, are not translated. On the other hand, mRNAs with mutations in exon 3 can normally produce long and highly unstable β chains that are not capable of combining with α chains to produce any kind of stable Hb tetramer. Therefore, in the former situation, a small excess of α chains in the recessive forms of β-thal trait only cause mild microcytic hypochromic indices, whereas in the later situation, excess α chains together with long unstable products, result in severe ineffective erythropoiesis in the dominant types. For this reason, these mutations in exon 3 are usually known as hyperunstable Hb variants rather than β-thal alleles.
Genotypic and phenotypic factors influencing the rate of progression in ABCA-4-related Stargardt disease
Published in Expert Review of Ophthalmology, 2021
Vincenzo Starace, Marco Battista, Maria Brambati, Matteo Pederzolli, Chiara Viganò, Alessandro Arrigo, Maria Vittoria Cicinelli, Francesco Bandello, Maurizio Battaglia Parodi
Missense mutations can sometimes be as severe as deleterious mutations, because of the variable impact of the mutation on the protein’s folding or localization[48]. Examples of likely severe ABCA4 missense mutations include p.Leu541Pro, p.Arg602Trp, p.Thr1019Met, p.Leu1940Pro, and p.His1838Asp[45]. Previous authors agreed in associating truncating and severely misfolding mutations with an earlier onset and a worse course of the disease [49,50]. An Italian study identified a strong association of deletions, stop codons, and insertions with a severe STGD phenotype, with high clinical variability among eyes bearing similar mutations[51]. The c.5882 G > A mutation was associated with better visual prognosis[29], whereas c.5461–10 T > C mutation correlated with earlier STGD onset and worse visual projections[52].
Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility
Published in Human Fertility, 2020
Zohreh Heidary, Kioomars Saliminejad, Majid Zaki-Dizaji, Hamid Reza Khorram Khorshid
DNAI1 (dynein axonemal intermediate chain 1), DNAH5 (dynein axonemal heavy chain 5) and DNAH11 (dynein axonemal heavy chain 11) genes encode three proteins belonging to the axonemal dynein cluster, particularly expressed in testis and trachea (Zuccarello, Ferlin, Cazzadore, et al., 2008). Dynein is a family of cytoskeletal motor proteins that move along microtubules in cells. There are two kinds of dynein: (i) cytoplasmic and (ii) axonemal. They convert the chemical energy stored in ATP to mechanical work (Roberts, Kon, Knight, Sutoh, & Burgess, 2013). Three missense mutations (R663C in DNAI1, E2666D in DNAH5 and I13040V in DNAH11) have been associated with AZS, with a frequency of 8.0%. These missense mutations cause substitution of amino acids, which are essential for the protein structure. These three proteins in the axonemal dynein cluster permanently attached to the A tubule of each outer microtubule doublet and transiently attached to the B tubule of the adjacent microtubule doublet, to generate a sliding motion (Zuccarello, Ferlin, Cazzadore, et al., 2008).