Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912161639> ?p ?o ?g. }
- W2912161639 endingPage "157" @default.
- W2912161639 startingPage "147" @default.
- W2912161639 abstract "Dilated cardiomyopathy (DCM) is a leading cause of morbidity and mortality worldwide; yet how genetic variation and environmental factors impact DCM heritability remains unclear. Here, we report that compound genetic interactions between DNA sequence variants contribute to the complex heritability of DCM. By using genetic data from a large family with a history of DCM, we discovered that heterozygous sequence variants in the TROPOMYOSIN 1 (TPM1) and VINCULIN (VCL) genes cosegregate in individuals affected by DCM. In vitro studies of patient-derived and isogenic human-pluripotent-stem-cell-derived cardiomyocytes that were genome-edited via CRISPR to create an allelic series of TPM1 and VCL variants revealed that cardiomyocytes with both TPM1 and VCL variants display reduced contractility and sarcomeres that are less organized. Analyses of mice genetically engineered to harbour these human TPM1 and VCL variants show that stress on the heart may also influence the variable penetrance and expressivity of DCM-associated genetic variants in vivo. We conclude that compound genetic variants can interact combinatorially to induce DCM, particularly when influenced by other disease-provoking stressors. Genome-edited human pluripotent stem cells and genome-edited mouse models reveal that combinatorial genetic interactions contribute to the complex genetic heritability of human cardiomyopathy." @default.
- W2912161639 created "2019-02-21" @default.
- W2912161639 creator A5000769574 @default.
- W2912161639 creator A5007656986 @default.
- W2912161639 creator A5021466887 @default.
- W2912161639 creator A5032578850 @default.
- W2912161639 creator A5033696938 @default.
- W2912161639 creator A5037087448 @default.
- W2912161639 creator A5039405858 @default.
- W2912161639 creator A5039775565 @default.
- W2912161639 creator A5043931957 @default.
- W2912161639 creator A5049101165 @default.
- W2912161639 creator A5052344288 @default.
- W2912161639 creator A5063129296 @default.
- W2912161639 creator A5070968328 @default.
- W2912161639 creator A5076506932 @default.
- W2912161639 creator A5077225971 @default.
- W2912161639 creator A5081897240 @default.
- W2912161639 creator A5085873765 @default.
- W2912161639 creator A5085935898 @default.
- W2912161639 creator A5087269715 @default.
- W2912161639 date "2019-02-07" @default.
- W2912161639 modified "2023-10-16" @default.
- W2912161639 title "Combinatorial interactions of genetic variants in human cardiomyopathy" @default.
- W2912161639 cites W1587510658 @default.
- W2912161639 cites W1635804580 @default.
- W2912161639 cites W1898753515 @default.
- W2912161639 cites W1965139838 @default.
- W2912161639 cites W1966701241 @default.
- W2912161639 cites W1970288681 @default.
- W2912161639 cites W1979363352 @default.
- W2912161639 cites W1982300430 @default.
- W2912161639 cites W1984069598 @default.
- W2912161639 cites W1991507611 @default.
- W2912161639 cites W2034685620 @default.
- W2912161639 cites W2036176224 @default.
- W2912161639 cites W2040422211 @default.
- W2912161639 cites W2052302545 @default.
- W2912161639 cites W2066231767 @default.
- W2912161639 cites W2069759472 @default.
- W2912161639 cites W2083599207 @default.
- W2912161639 cites W2090881549 @default.
- W2912161639 cites W2096173332 @default.
- W2912161639 cites W2096465161 @default.
- W2912161639 cites W2097149135 @default.
- W2912161639 cites W2097555314 @default.
- W2912161639 cites W2099169137 @default.
- W2912161639 cites W2101648125 @default.
- W2912161639 cites W2105306382 @default.
- W2912161639 cites W2113202677 @default.
- W2912161639 cites W2117928677 @default.
- W2912161639 cites W2126718294 @default.
- W2912161639 cites W2131062132 @default.
- W2912161639 cites W2137802443 @default.
- W2912161639 cites W2148134248 @default.
- W2912161639 cites W2164977353 @default.
- W2912161639 cites W2169456326 @default.
- W2912161639 cites W2170039745 @default.
- W2912161639 cites W2171243928 @default.
- W2912161639 cites W2179438025 @default.
- W2912161639 cites W2191641478 @default.
- W2912161639 cites W2197124664 @default.
- W2912161639 cites W2256016639 @default.
- W2912161639 cites W2261410143 @default.
- W2912161639 cites W2323326409 @default.
- W2912161639 cites W2341581870 @default.
- W2912161639 cites W2397641207 @default.
- W2912161639 cites W2532808087 @default.
- W2912161639 cites W2549881333 @default.
- W2912161639 cites W2580792129 @default.
- W2912161639 cites W2592746394 @default.
- W2912161639 cites W2604078450 @default.
- W2912161639 cites W2604155358 @default.
- W2912161639 cites W2634858582 @default.
- W2912161639 cites W2638131009 @default.
- W2912161639 cites W869626853 @default.
- W2912161639 doi "https://doi.org/10.1038/s41551-019-0348-9" @default.
- W2912161639 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6433174" @default.
- W2912161639 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30923642" @default.
- W2912161639 hasPublicationYear "2019" @default.
- W2912161639 type Work @default.
- W2912161639 sameAs 2912161639 @default.
- W2912161639 citedByCount "38" @default.
- W2912161639 countsByYear W29121616392019 @default.
- W2912161639 countsByYear W29121616392020 @default.
- W2912161639 countsByYear W29121616392021 @default.
- W2912161639 countsByYear W29121616392022 @default.
- W2912161639 countsByYear W29121616392023 @default.
- W2912161639 crossrefType "journal-article" @default.
- W2912161639 hasAuthorship W2912161639A5000769574 @default.
- W2912161639 hasAuthorship W2912161639A5007656986 @default.
- W2912161639 hasAuthorship W2912161639A5021466887 @default.
- W2912161639 hasAuthorship W2912161639A5032578850 @default.
- W2912161639 hasAuthorship W2912161639A5033696938 @default.
- W2912161639 hasAuthorship W2912161639A5037087448 @default.
- W2912161639 hasAuthorship W2912161639A5039405858 @default.
- W2912161639 hasAuthorship W2912161639A5039775565 @default.
- W2912161639 hasAuthorship W2912161639A5043931957 @default.