Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024951844> ?p ?o ?g. }
- W2024951844 endingPage "e0118413" @default.
- W2024951844 startingPage "e0118413" @default.
- W2024951844 abstract "The phenotype of many regulatory circuits in which mutations can cause complex, polygenic diseases is to some extent robust to DNA mutations that affect circuit components. Here I demonstrate how such mutational robustness can prevent the discovery of genetic disease determinants. To make my case, I use a mathematical model of the insulin signaling pathway implicated in type 2 diabetes, whose signaling output is governed by 15 genetically determined parameters. Using multiple complementary measures of a parameter's importance for this phenotype, I show that any one disease determinant that is crucial in one genetic background will be virtually irrelevant in other backgrounds. In an evolving population that drifts through the parameter space of this or other robust circuits through DNA mutations, the genetic changes that can cause disease will vary randomly over time. I call this phenomenon causal drift. It means that mutations causing disease in one (human or non-human) population may have no effect in another population, and vice versa. Causal drift casts doubt on our ability to infer the molecular mechanisms of complex diseases from non-human model organisms." @default.
- W2024951844 created "2016-06-24" @default.
- W2024951844 creator A5079730045 @default.
- W2024951844 date "2015-03-16" @default.
- W2024951844 modified "2023-10-02" @default.
- W2024951844 title "Causal Drift, Robust Signaling, and Complex Disease" @default.
- W2024951844 cites W1598569053 @default.
- W2024951844 cites W1623155147 @default.
- W2024951844 cites W1773423156 @default.
- W2024951844 cites W1873654689 @default.
- W2024951844 cites W1969194147 @default.
- W2024951844 cites W1970409419 @default.
- W2024951844 cites W1973358400 @default.
- W2024951844 cites W1973372369 @default.
- W2024951844 cites W1973423816 @default.
- W2024951844 cites W1974075629 @default.
- W2024951844 cites W1976577632 @default.
- W2024951844 cites W1978641328 @default.
- W2024951844 cites W1980647259 @default.
- W2024951844 cites W1980991473 @default.
- W2024951844 cites W1982688466 @default.
- W2024951844 cites W1998112065 @default.
- W2024951844 cites W1999286346 @default.
- W2024951844 cites W1999613863 @default.
- W2024951844 cites W2000163865 @default.
- W2024951844 cites W2002047357 @default.
- W2024951844 cites W2009599202 @default.
- W2024951844 cites W2010763118 @default.
- W2024951844 cites W2012870455 @default.
- W2024951844 cites W2014967694 @default.
- W2024951844 cites W2021708142 @default.
- W2024951844 cites W2022425690 @default.
- W2024951844 cites W2024913341 @default.
- W2024951844 cites W2027905390 @default.
- W2024951844 cites W2031792984 @default.
- W2024951844 cites W2033781181 @default.
- W2024951844 cites W2036227669 @default.
- W2024951844 cites W2038081709 @default.
- W2024951844 cites W2043276874 @default.
- W2024951844 cites W2043851046 @default.
- W2024951844 cites W2048755332 @default.
- W2024951844 cites W2049648266 @default.
- W2024951844 cites W2054583174 @default.
- W2024951844 cites W2056878233 @default.
- W2024951844 cites W2058138221 @default.
- W2024951844 cites W2060214843 @default.
- W2024951844 cites W2061866413 @default.
- W2024951844 cites W2062042643 @default.
- W2024951844 cites W2062546738 @default.
- W2024951844 cites W206344144 @default.
- W2024951844 cites W2063661977 @default.
- W2024951844 cites W2065121736 @default.
- W2024951844 cites W2065151681 @default.
- W2024951844 cites W2069647329 @default.
- W2024951844 cites W2071629571 @default.
- W2024951844 cites W2073378157 @default.
- W2024951844 cites W2076814714 @default.
- W2024951844 cites W2077259222 @default.
- W2024951844 cites W2078920527 @default.
- W2024951844 cites W2082890120 @default.
- W2024951844 cites W2084610168 @default.
- W2024951844 cites W2092309107 @default.
- W2024951844 cites W2092414667 @default.
- W2024951844 cites W2094945089 @default.
- W2024951844 cites W2098597355 @default.
- W2024951844 cites W2102744682 @default.
- W2024951844 cites W2104093114 @default.
- W2024951844 cites W2105437542 @default.
- W2024951844 cites W2106779017 @default.
- W2024951844 cites W2110808585 @default.
- W2024951844 cites W2111184079 @default.
- W2024951844 cites W2114124738 @default.
- W2024951844 cites W2115300553 @default.
- W2024951844 cites W2116626049 @default.
- W2024951844 cites W2120852510 @default.
- W2024951844 cites W2120930759 @default.
- W2024951844 cites W2122473859 @default.
- W2024951844 cites W2126796035 @default.
- W2024951844 cites W2129618124 @default.
- W2024951844 cites W2134783591 @default.
- W2024951844 cites W2135262279 @default.
- W2024951844 cites W2135409182 @default.
- W2024951844 cites W2135447862 @default.
- W2024951844 cites W2139241427 @default.
- W2024951844 cites W2140140747 @default.
- W2024951844 cites W2146977706 @default.
- W2024951844 cites W2147777139 @default.
- W2024951844 cites W2149199536 @default.
- W2024951844 cites W2150732692 @default.
- W2024951844 cites W2151233592 @default.
- W2024951844 cites W2151316409 @default.
- W2024951844 cites W2155838479 @default.
- W2024951844 cites W2158693433 @default.
- W2024951844 cites W2161304688 @default.
- W2024951844 cites W2161809910 @default.
- W2024951844 cites W2162791825 @default.
- W2024951844 cites W2163924952 @default.
- W2024951844 cites W2166256210 @default.