Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development.
Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development.
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DOI：
10.1242/dmm.011726
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发表时间：
2013-09
影响因子：
4.3
通讯作者：
Goessling W
中科院分区：
文献类型：
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作者：
Liu LY;Fox CS;North TE;Goessling W
Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf) and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10) decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50) decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.
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影响因子：
3.7
作者：
Rzehak P;Thijs C;Standl M;Mommers M;Glaser C;Jansen E;Klopp N;Koppelman GH;Singmann P;Postma DS;Sausenthaler S;Dagnelie PC;van den Brandt PA;Koletzko B;Heinrich J;KOALA study group;LISA study group
通讯作者：
LISA study group
DOI：
10.1111/j.1440-1746.2011.06807.x
发表时间：
2012-02-01
影响因子：
4.1
作者：
Kucera, Otto;Rousar, Tomas;Cervinkova, Zuzana
通讯作者：
Cervinkova, Zuzana
影响因子：
13.5
作者：
Sookoian, Silvia;Pirola, Carlos J.
通讯作者：
Pirola, Carlos J.
影响因子：
20.1
作者：
Verschuren L;Kooistra T;Bernhagen J;Voshol PJ;Ouwens DM;van Erk M;de Vries-van der Weij J;Leng L;van Bockel JH;van Dijk KW;Fingerle-Rowson G;Bucala R;Kleemann R
通讯作者：
Kleemann R
影响因子：
64.8
作者：
通讯作者：
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