Data for: A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects

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 p..., , # Data for: A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects

Dataset DOI: [10.5061/dryad.hx3ffbgs1](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...,

本研究旨在探索全新方法，以鉴定先天性心脏病（CHDs，congenital heart defects）的遗传病因。我们结合了对受强烈选择约束的基因的分析，以及已发表的胚胎心脏转录组数据，最终鉴定出200余个先天性心脏病新候选基因。我们借助蛋白质-蛋白质相互作用（PPI，protein-protein interaction）网络分析，识别出一个功能相关的子网络，该子网既包含已知的先天性心脏病相关基因，也涵盖了编码蛋白酶体因子的基因，尤其是POMP、PSMA6、PSMA7、PSMD3及PSMD6。我们通过在斑马鱼胚胎中开展CRISPR靶向实验，初步明确了该PPI子网络基因在心脏发育中的作用。随后，我们针对该子网络中的两个蛋白酶体基因——pomp与psmd6，利用CRISPR技术构建了新型突变斑马鱼品系。研究证实，蛋白酶体基因功能缺失会导致斑马鱼心脏发育异常，具体表现为心脏形态畸形、心肌细胞起泡以及流出道发育不全。我们还发现pomp与psmd6突变体存在心脏功能缺陷……

# 关联数据集：《系统遗传学方法揭示蛋白酶体因子在心脏发育与先天性心脏病中的作用》
数据集DOI: [10.5061/dryad.hx3ffbgs1](10.5061/dryad.hx3ffbgs1)

## 数据与文件结构说明
本数据集包含前述发表论文《系统遗传学方法揭示蛋白酶体因子在心脏发育与先天性心脏病（CHDs）中的作用》中所有图表对应的原始实验数据。该研究借助基于CRISPR的基因编辑手段，在斑马鱼中特异性敲除候选心脏缺陷相关基因，揭示了蛋白酶体基因在心脏发育中的全新功能。研究证实，pomp与psmd6这两个蛋白酶体基因的功能缺失会引发斑马鱼心脏发育异常。本研究表明蛋白酶体基因家族参与心脏发育过程，加深了我们对先天性心脏病致病机制的理解。本数据集的生成方法详见上述发表论文。

### 文件与变量说明……