Data for: A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects
Data files
Aug 17, 2025 version files 81.06 KB
-
Fig3G0CRISPRdata.csv
16.41 KB
-
Fig4HeartMorphology.csv
198 B
-
Fig4pompandpsmd6survival.csv
4.65 KB
-
Fig4qPCR.csv
7.14 KB
-
Fig5Morphologymyl7GFP48hr.csv
2.53 KB
-
Fig5Morphologymyl7GFP72hr.csv
3.95 KB
-
Fig5myl7DIGAPinsitus.csv
708 B
-
Fig6Morphologymyl7GFP96hr.csv
4.29 KB
-
Fig7Heartfunction.csv
19.33 KB
-
Fig8alphaactinin96hr.csv
1.42 KB
-
Fig8Myofiberwidths.csv
6.51 KB
-
Fig8Sarcomerelengths.csv
6.60 KB
-
Fig9elnbmeasurements.csv
2.25 KB
-
README.md
5.07 KB
Abstract
In this study, we sought to take a new approach to identify genetic causes of CHDs. By combining analyses of genes that are under strong selective constraint along with published embryonic heart transcriptomes, we identified over 200 new candidate genes for CHDs. We utilized protein-protein interaction (PPI) network analysis to identify a functionally-related subnetwork consisting of known CHD genes as well as genes encoding proteasome factors, in particular POMP, PSMA6, PSMA7, PSMD3, and PSMD6. We used CRISPR targeting in zebrafish embryos to preliminarily identify roles for the PPI subnetwork genes in heart development. We then used CRISPR to create new mutant zebrafish strains for two of the proteasome genes in the subnetwork: pomp and psmd6. We show that loss of proteasome gene functions leads to defects in zebrafish heart development, including dysmorphic hearts, myocardial cell blebbing, and reduced outflow tracts. We also identified deficits in cardiac function in pomp and psmd6 mutants. These heart defects resemble those seen in zebrafish mutants for known CHD genes and other critical heart development genes. Our study provides a novel systems genetics approach to further our understanding of the genetic causes of human CHDs.
Dataset DOI: 10.5061/dryad.hx3ffbgs1
Description of the data and file structure
The data presented here is an original dataset of the raw data underlying the figures in the publication A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects (CHDs). In this publication, we use a CRISPR-based approach in zebrafish to specifically eliminate candidate heart defect genes and reveal new roles for proteasome genes in heart development. We show that loss of functions of two proteasome genes, pomp and psmd6, leads to zebrafish heart defects. This study shows that a proteasome gene family contributes to heart development, advancing our understanding of the causes of CHDs. The data was generated using the methods described in the resulting publication.
Files and variables
This Data file contains the following tables of raw data generated for this study.
List of Tables provided
Fig3G0CRISPRdata.csv This table provides the raw data underlying the graphs shown in Fig 3C and Fig 3D. Data shown are results of CRISPR guide injections for genes shown, and zebrafish embryo heart phenotypes scored. ID, clutch of embryos. hHpf hours post fertilization. sev severe. mod moderate.
Fig4qPCR.csv This table provides the raw data underlying the graphs shown in Fig. 4C and Fig. 4D. The data shown are results of qPCR analysis on control versus mutant embryos for the genes shown. qPCR, quantitative polymerase chain reaction. WT, wild type. Mut, mutant. Cq, cycle threshold. ddCt, normalized cycle threshold.
Fig4HeartMorphology.csv This table provides the raw data underlying the graph shown in Fig. 4T. The graph shows frequencies of heart defect categories observed in 4-day-old larvae. WT, wild type. DMSO, dimethyl sulfoxide.
Fig4pompandpsmd6survival.csv This table provides the raw data underlying the graph shown in Fig. 4U, a survival plot of two independent clutches each of pomp and psmd6 embryos. Hpf, hours post fertilization.
Fig5myl7DIGAPinsitus.csv This table provides the raw data for the embryo numbers provided in the legend for the images shown in Fig. 5A-F. Data shown are heart phenotypes scored for myl7 staining using in situ hybridization (DIG AP). WT, wild type. 18s, 18 somite stage. Hpf, hours post fertilization.
Fig5Morphologymyl7GFP48hr.csv This table provides the raw data for the embryo numbers provided in the legend for the images shown in Fig. 5G-I. Data shown are heart phenotypes scored for myl7 staining using GFP (green fluorescent protein) expression. WT, wild type. hHr hours of development. hHpf hours post fertilization. Mut, mutant. dysm, dysmorphic. n, numbers. Y, N, yes, no.
Fig5Morphologymyl7GFP72hr.csv This table provides the raw data for the embryo numbers provided in the legend for the images shown in Fig. 5G-I. Data shown are heart phenotypes scored for myl7 staining using GFP (green fluorescent protein) expression. WT, wild type. Hr, hours of development. hHpf hours post fertilization. Mut, mutant. dysm, dysmorphic. n, numbers. Y, N, yes, no. dDegen degenerating.
Fig6Morphologymyl7GFP96hr.csv This table provides the raw data for the embryo numbers provided in the graph shown in Fig. 6G. Data shown are protruding cardiomyocytes scored for myl7 staining using GFP (green fluorescent protein) expression in 4 dpf heart. IHC, immunohistochemistry. WT, wild type. Hpf, hours post fertilization. dpf, days post fertilization. Mut, mutant. dysm, dysmorphic. n, numbers. Y, N, yes, no. E, elongated. S, severe.
Fig7Heartfunction.csv This table provides the raw data for the heart measurements provided in the graphs shown in Fig. 7G-L. um, microns. HR, heart rate. bBpm beats per minute. MUT, mutant. WT, wild type.
Fig8alphaactinin96hr.csv This table provides the raw data for embryo numbers describing the images presented in Fig. 8A-C. The data shown are heart phenotypes scored for alpha-actinin staining. WT, wild type. Hr, hours of development. Hpf, hours post fertilization. Mut, mutant. dysm, dysmorphic. n, numbers. Y, N, yes, no.
Fig8Sarcomerelengths.csv This table provides the raw data for the measurements provided in the graph shown in Fig. 8F. WT, wild type. Mut, mutant.Avgg, average. Um, microns. St dev, standard deviation.
Fig8Myofiberwidths.csv This table provides the raw data for the measurements provided in the graph shown in Fig. 8G. WT, wild type. Mut, mutant. Avg, average. um, microns.
Fig9elnbmeasurements.csv This table provides the raw data for the measurements of the expression domain of the gene elnb provided in the graph shown in Fig. 9G-H. WT, wild type. um, microns. ID, inner diameter. OD, outer diameter. Hpf, hours post fertilization.
Access information
Other publicly accessible locations of the data: