Mutation taster

What is Combined Annotation Dependent Depletion (CADD)? CADD is a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletions variants in the human genome. While many variant annotation and scoring tools are around, most annotations tend to exploit a single information type (e.g. conservation) and/or are restricted in scope (e.g. to missense changes). Thus, a broadly applicable metric that objectively weights and integrates diverse information is needed. Combined Annotation Dependent Depletion (CADD) is a framework that integrates multiple annotations into one metric by contrasting variants that survived natural selection with simulated mutations. C-scores strongly correlate with allelic diversity, pathogenicity of both coding and non-coding variants, and experimentally measured regulatory effects, and also highly rank causal variants within individual genome sequences. Finally, C-scores of complex trait-associated variants from genome-wide association studies (GWAS) are significantly higher than matched controls and correlate with study sample size, likely reflecting the increased accuracy of larger GWAS. CADD can quantitatively prioritize functional, deleterious, and disease causal variants across a wide range of functional categories, effect sizes and genetic architectures and can be used prioritize causal variation in both research and clinical settings. In addition to this website, CADD has been described in three publications. Th...

Share on Pinterest A supertaster is a person who tastes certain flavors and foods more strongly than other people. The human tongue is wrapped in taste buds (fungiform papillae). The small, mushroom-shaped bumps are covered with taste receptors that bind to the molecules from your food and help tell your brain what you’re eating. Some people have more of these taste buds and receptors, so their perception of flavor is stronger than the average person. They are known as supertasters. Supertasters are particularly sensitive to Supertasters are born with this Scientists believe most supertasters have the gene TAS2R38, which increases bitterness perception. The gene makes supertasters sensitive to bitter flavors in all foods and drinks. People with this gene are particularly sensitive to a chemical called 6-n-propylthiouracil (PROP). About On the opposite end of the taste spectrum, non-tasters have fewer taste buds than the average person. Foods taste less flavorful and vibrant to these individuals, who make up about a The largest group, however, is medium or average tasters. They are the remaining Taste buds can detect five primary flavors: • sweet • salt • bitter • sour • umami For supertasters, the fungiform papillae pick up bitter flavors more easily. The more sensitive taste buds are, the more intense the flavors may be. Supertasters may have more, stronger taste buds Supertasting abilities may be the result of tongues that are more densely crowded with taste buds, or fun...

\( \newcommand\) • • • • • • • • • • Learning Objectives Goals: • To understand basic PCR and gel electrophoresis • To understand basic DNA mutation detection • To learn how restriction enzymes are incorporated in biotechnology Student Learning Outcomes: Upon completion of this lab, students will be able to: • Understand SNPs • Know how to perform a DNA extraction, PCR, and restriction digest • Know how to interpret a DNA gel after electrophoresis Introduction Every organism on Earth has a different way to perceive the world due to their individual life experiences as well as their genetic make-up. Humans are no different; every individual has their own experiences that shapes their world perception but so too does their DNA. You may be surprised to learn that, 99.9% of the human genome is identical from one individual to the next, and it is the 0.1% difference that makes each individual unique. Some of these differences can affect our sensory systems and how we perceive the natural world. For example, over time we have learned which things taste good and are good for us while simultaneously learning which things taste bad or are bad for us. Specifically, bitter compounds are closely associated to toxic substances in nature. The way we know things taste bitter, or any other flavor for that matter, is because we have special chemical receptors in our mouth and nose that bind molecules in our food and send signals to the brain telling it what the food tastes like. Figure 1:...

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicat...

From the Department of Neurology (Y.O., I.T.-I., S.S., I.Y.), Faculty of Medicine and Graduate School of Medicine, Hokkaido University; Department of Diagnostic Imaging (T.H.), Hokkaido University Graduate School of Medicine; and Department of Neurology (T.Y.), Kyoto Prefectural University of Medicine. • • • From the Department of Neurology (Y.O., I.T.-I., S.S., I.Y.), Faculty of Medicine and Graduate School of Medicine, Hokkaido University; Department of Diagnostic Imaging (T.H.), Hokkaido University Graduate School of Medicine; and Department of Neurology (T.Y.), Kyoto Prefectural University of Medicine. • • • • Oy-sters • In adult-onset Alexander disease, the medulla oblongata may swell transiently and atrophy over time. • In order to avoid sudden respiratory decompensation, patients with adult-onset Alexander disease should be given anticipatory guidance and undergo periodic laryngoscopy, even if the patient has been stable for a long time. Alexander disease is a rare hereditary neurodegenerative disorder caused by variants of the glial fibrillary acid protein ( GFAP) gene. Case Report A 45-year-old man presented at our department with unsteadiness while walking. He was unable to walk in tandem gait, and had nystagmus, diplopia, and slight dysarthria. Both his parents had died of a stroke. His brother and 3 daughters were in good health. Serum angiotensin-converting enzyme levels were not elevated, and the results were negative for interferon-γ release assay, β-D-gluca...

✖ Example 1: Disease mutation CHRND_L63P This single base exchange in the CHRND gene is listed in NCBI ClinVar as a known disease-causing variant (dbSNP:rs121909508) for MYASTHENIC SYNDROME, CONGENITAL, FAST-CHANNEL, OMIM 100720#0013). It results in an amino acid exchange from leucin to proline. The involved amino acid residue is part of a functional domain (topo domain) and is highly conserved (amino acids identical in all homologes). As a consequence of the mutation, the topo domain is lost. The phyloP and phastCons values for the changed nucleotide are very high, again indicating strong evolutionary conservation. The mutation is identical to the one in ✖ Example 2: Disease mutation CHRND_L63P This single base exchange in the CHRND gene is listed in NCBI ClinVar as a known disease-causing variant (dbSNP:rs121909508) for MYASTHENIC SYNDROME, CONGENITAL, FAST-CHANNEL, OMIM 100720#0013). It results in an amino acid exchange from leucin to proline. The involved amino acid residue is part of a functional domain (topo domain) and is highly conserved (amino acids identical in all homologes). As a consequence of the mutation, the topo domain is lost. The phyloP and phastCons values for the changed nucleotide are very high, again indicating strong evolutionary conservation. The mutation is identical to the one in ✖ Example 3: Polymorphism AGRN_g.28670_28671delAG This example is a deletion that was found more than 4 times in the 1000Genomes Project (TGP) in homozygous state. There...

MutationTaster Content Description In silico tool to predict the disease-causing potential of DNA variants Contact Authors Jana Marie Schwarz and Dominik Seelow Primary citation Access Website .mutationtaster .org MutationTaster is a free web-based application to evaluate DNA sequence variants for their disease-causing potential. The software performs a battery of in silico tests to estimate the impact of the variant on the gene product / protein. Tests are made on both, protein and DNA level, MutationTaster is hence not limited to Background [ ] Many Approach and tests [ ] Mutation Taster is written in • Silent synonymous or intronic alterations that do not lead to an amino acid exchange • Mutations that affect a single amino acid • Mutations causing complex changes in the amino acid sequence (such as Multiple tests are performed to determine the nature of the given SNP. These tests comprise (among others): • amino acid substitution(s) • conservation of affected amino acid(s) • potential loss of functional protein domains • length of protein • effect on splicing • conservation on DNA level (phastCons / phyloP) • potential abrogation of regulatory elements (such as transcription factor binding sites) Integrated data sources (among others): • Ensembl • UniProt • ClinVar • ExAC • 1000 Genomes Project • phyloP • phastCons The single results are then assessed by a Importantly, the predictions of clinical effects of mutations suffer from a lack of specificity, which appears to ...