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Definition of HLA-Dw Determinants Using Homozygous Typing Cells and the Mixed Lymphocyte Culture
Published in M. Kam, Jeffrey L. Bidwell, Handbook of HLA TYPING TECHNIQUES, 2020
The observation that certain Dw specificities were associated with specific DQ alleles led to the suggestion that the Dw specificities were also determined by the HLA-DQ genes.40 However, DNA sequencing data indicate that the main contribution to the stimulation associated with the definition of Dw determinants is given by variation in the first domain of the DRB genes, i.e., DRB1, DRB3, and DRB5 (no polymorphism of the DRB4 gene has yet been identified41). For instance, specific amino acid substitutions in the DRB1 gene of DR4 haplotypes correlate with the associated Dw subtypes.25 Furthermore, DNA sequencing data obtained thus far also indicate that amino acid substitutions at position 86 (and possible 85) of the first domain are directly or indirectly involved in the formation of the epitope recognized by alloreactive T cell, and thus may be crucial in defining the Dw determinants.42-44
Inherited Differences in Alpha1-Antitrypsin
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
It is difficult to accept two amino acid substitutions located far apart in the amino acid sequence as the consequence of a single mutational event. The substitution of lysine for glutamic acid can best explain the electrophoretic difference. The underlying mutation would be a nucleotide base transition from cytosine to thymine.
Haematological disorders
Published in Judy Bothamley, Maureen Boyle, Medical Conditions Affecting Pregnancy and Childbirth, 2020
SCDs are abnormalities of the quality of the haemoglobin. A genetically inherited amino acid substitution results in the production of an abnormal haemoglobin that can sickle. More than 300 variant (abnormal) haemoglobins have been identified, although not all are clinically significant (Strong, 2006). Box 4.6 gives an overview of some of the significant variant combinations, the most common of which is sickle cell anaemia (HBSS).
MHC class II molecules on pancreatic cancer cells indicate a potential for neo-antigen-based immunotherapy
Published in OncoImmunology, 2022
Renato B. Baleeiro, Christian J. Bouwens, Peng Liu, Carmela Di Gioia, Louisa S. Chard Dunmall, Ai Nagano, Rathistevy Gangeswaran, Claude Chelala, Hemant M. Kocher, Nicholas R. Lemoine, Yaohe Wang
For the identification of potential neo-epitopes from the somatic missense mutations detected from exome sequencing analysis of 100 PDAC patients,46 exome sequencing data were used to compile a list of expressed somatic missense mutations. Amino-acid substitutions corresponding to each of the coding missense mutations were translated into a 29-mer amino acid FASTA sequence, with 14 amino acids flanking the mutated amino acid on each side. These 29-mer amino-acid sequences were evaluated through the MHC class II peptide–binding algorithm NetMHCIIpan-3.0 69 to identify high-affinity 15mer, neo-epitopes predicted to bind with high affinity to HLA-DP*04:01. Neo-epitopes were selected when mutated peptide fell within the 20% percentile rank and the corresponding wild type was above the 20%.
Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
Published in Infectious Diseases, 2022
Anne Tuiskunen Bäck, Johan Rasmuson, Therese Thunberg, Gregory Rankin, Julia Wigren Byström, Charlotta Andersson, Andreas Sjödin, Mattias Forsell, Clas Ahlm
Complete S segment sequencing of the PUUV isolate derived from the patient’s blood plasma, without any previous propagation in cell culture, revealed five amino acid substitutions compared to the Swedish reference strain Umea/hu: P233A in the N protein and D9G, D50E, K59R and N79S in the NS protein. The N protein is the most abundantly expressed PUUV protein and a major antigenic determinant, e.g. the major viral target antigen recognised by T cells [21] and has been shown in in vivo studies to harbour immunogenic domains throughout its length [22]. It has been suggested to influence the severity of endothelial permeability and capillary leakage, and antibodies against the N protein also appear before antibodies against the glycoproteins Gc and Gn [21]. The 90 amino acid long NS-protein encoded by an alternative internal ORF in the S segment is expressed by certain orthohantaviruses including PUUV, and is suggested to be important for down-regulating the interferon response during infection [23]. Whether these four amino acid substitutions of the NS-protein would have had an effect on the interferon response and thereby on the clinical outcome of the patient is unknown. The significance of these amino acid substitutions needs to be further studied in order to address this question.
Predicting the functional and structural consequences of nsSNPs in human methionine synthase gene using computational tools
Published in Systems Biology in Reproductive Medicine, 2019
Mansi Desai, Jenabhai B. Chauhan
The functionally deleterious nsSNPs of human MTR gene were predicted using five different computational tools namely SIFT (Sorting Intolerant from Tolerant; http://sift.jcvi.org/), PolyPhen2 (Polymorphism Phenotyping 2; http://genetics.bwh.harvard.edu/pph2/), PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org/index.php), SNAP2 (https://rostlab.org/services/snap/) and PMut (http://mmb.pcb.ub.es/pmut2005/). All are web-based tools predicting the functional consequences of amino acid substitution. SIFT classifies the nsSNPs into damaging and tolerated (Ng and Henikoff 2006). PolyPhen classifies them into probably damaging, possibly damaging, and benign (Ramensky et al. 2002). PROVEAN classifies the nsSNPs into deleterious and neutral (Choi et al. 2012). SNAP2 classifies the nsSNPs into effect and neutral (Yachdav et al. 2014). PMut classifies them into pathological and neutral variants (Ferrer-Costa et al. 2005).