Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000559685> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W2000559685 endingPage "15403" @default.
- W2000559685 startingPage "15398" @default.
- W2000559685 abstract "Most Mendelian diseases studied to date arise from mutations that lead to a single amino acid change in an encoded protein. An increasing number of complex diseases have also been associated with amino acid-changing single-nucleotide polymorphisms (coding SNPs, cSNPs), suggesting potential similarities between Mendelian and complex diseases at the molecular level. Here, we use two different evolutionary analyses to compare Mendelian and complex disease-associated cSNPs. In the first, we estimate the likelihood that a specific amino acid substitution in a protein will affect the protein's function, by using amino acid substitution scores derived from an alignment of related protein sequences and statistics from hidden Markov models. In the second, we use standard Ka/Ks ratios to make comparisons at the gene, rather than the individual amino acid, level. We find that Mendelian disease cSNPs have a very strong tendency to occur at highly conserved amino acid positions in proteins, suggesting that they generally have a severe impact on the function of the protein. Perhaps surprisingly, the distribution of amino acid substitution scores for complex disease cSNPs is dramatically different from the distribution for Mendelian disease cSNPs, and is indistinguishable from the distribution for normal human variation. Further, the distributions of Ka/Ks ratios for human and mouse orthologs indicate greater positive selection (or less negative selection) pressure on complex disease-associated genes, on average. These findings suggest that caution should be exercised when using Mendelian disease as a model for complex disease, at least with respect to molecular effects on protein function." @default.
- W2000559685 created "2016-06-24" @default.
- W2000559685 creator A5016853551 @default.
- W2000559685 creator A5028956069 @default.
- W2000559685 date "2004-10-18" @default.
- W2000559685 modified "2023-10-16" @default.
- W2000559685 title "Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: Evolutionary evidence for differences in molecular effects" @default.
- W2000559685 cites W1547256603 @default.
- W2000559685 cites W1838763289 @default.
- W2000559685 cites W1965933400 @default.
- W2000559685 cites W1977906002 @default.
- W2000559685 cites W1985849948 @default.
- W2000559685 cites W2031946640 @default.
- W2000559685 cites W2044573154 @default.
- W2000559685 cites W2051356295 @default.
- W2000559685 cites W2062699991 @default.
- W2000559685 cites W2065435420 @default.
- W2000559685 cites W2085020944 @default.
- W2000559685 cites W2096525273 @default.
- W2000559685 cites W2098425296 @default.
- W2000559685 cites W2122004833 @default.
- W2000559685 cites W2122732537 @default.
- W2000559685 cites W2128969076 @default.
- W2000559685 cites W2141481588 @default.
- W2000559685 cites W2143249342 @default.
- W2000559685 cites W2146986827 @default.
- W2000559685 cites W2149195137 @default.
- W2000559685 cites W2160993714 @default.
- W2000559685 cites W2163500926 @default.
- W2000559685 cites W2165270659 @default.
- W2000559685 cites W2165419403 @default.
- W2000559685 doi "https://doi.org/10.1073/pnas.0404380101" @default.
- W2000559685 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/523449" @default.
- W2000559685 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15492219" @default.
- W2000559685 hasPublicationYear "2004" @default.
- W2000559685 type Work @default.
- W2000559685 sameAs 2000559685 @default.
- W2000559685 citedByCount "255" @default.
- W2000559685 countsByYear W20005596852012 @default.
- W2000559685 countsByYear W20005596852013 @default.
- W2000559685 countsByYear W20005596852014 @default.
- W2000559685 countsByYear W20005596852015 @default.
- W2000559685 countsByYear W20005596852016 @default.
- W2000559685 countsByYear W20005596852017 @default.
- W2000559685 countsByYear W20005596852018 @default.
- W2000559685 countsByYear W20005596852019 @default.
- W2000559685 countsByYear W20005596852020 @default.
- W2000559685 countsByYear W20005596852021 @default.
- W2000559685 countsByYear W20005596852022 @default.
- W2000559685 countsByYear W20005596852023 @default.
- W2000559685 crossrefType "journal-article" @default.
- W2000559685 hasAuthorship W2000559685A5016853551 @default.
- W2000559685 hasAuthorship W2000559685A5028956069 @default.
- W2000559685 hasBestOaLocation W20005596851 @default.
- W2000559685 hasConcept C104317684 @default.
- W2000559685 hasConcept C135763542 @default.
- W2000559685 hasConcept C141231307 @default.
- W2000559685 hasConcept C153209595 @default.
- W2000559685 hasConcept C175783326 @default.
- W2000559685 hasConcept C515207424 @default.
- W2000559685 hasConcept C54355233 @default.
- W2000559685 hasConcept C7386963 @default.
- W2000559685 hasConcept C86803240 @default.
- W2000559685 hasConceptScore W2000559685C104317684 @default.
- W2000559685 hasConceptScore W2000559685C135763542 @default.
- W2000559685 hasConceptScore W2000559685C141231307 @default.
- W2000559685 hasConceptScore W2000559685C153209595 @default.
- W2000559685 hasConceptScore W2000559685C175783326 @default.
- W2000559685 hasConceptScore W2000559685C515207424 @default.
- W2000559685 hasConceptScore W2000559685C54355233 @default.
- W2000559685 hasConceptScore W2000559685C7386963 @default.
- W2000559685 hasConceptScore W2000559685C86803240 @default.
- W2000559685 hasIssue "43" @default.
- W2000559685 hasLocation W20005596851 @default.
- W2000559685 hasLocation W20005596852 @default.
- W2000559685 hasLocation W20005596853 @default.
- W2000559685 hasLocation W20005596854 @default.
- W2000559685 hasOpenAccess W2000559685 @default.
- W2000559685 hasPrimaryLocation W20005596851 @default.
- W2000559685 hasRelatedWork W1506237483 @default.
- W2000559685 hasRelatedWork W1571735821 @default.
- W2000559685 hasRelatedWork W1796126005 @default.
- W2000559685 hasRelatedWork W1828948498 @default.
- W2000559685 hasRelatedWork W2029056863 @default.
- W2000559685 hasRelatedWork W2057739827 @default.
- W2000559685 hasRelatedWork W2097988366 @default.
- W2000559685 hasRelatedWork W2156830367 @default.
- W2000559685 hasRelatedWork W2172076792 @default.
- W2000559685 hasRelatedWork W3032357680 @default.
- W2000559685 hasVolume "101" @default.
- W2000559685 isParatext "false" @default.
- W2000559685 isRetracted "false" @default.
- W2000559685 magId "2000559685" @default.
- W2000559685 workType "article" @default.