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Abstract：
The genetic reference population of recombinant inbred BXD mice has been derived from crosses between C57BL/6J and DBA/2J strains. The DBA/2J parent exhibits cardiomyopathy phenotypes, whereas C57BL/6J has normal heart. BXD mice are sequenced for studying genetic interactions in cardiomyopathies. The study aimed to assess cardiomyopathy traits in BXDs and investigate the quantitative genetic architecture of those traits. Echocardiography, blood pressure, and cardiomyocyte size parameters obtained from 44 strains of BXD family (n > 5/sex) at 4-5 mo of age were associated with heart transcriptomes and expression quantitative trait loci (eQTL) mapping was performed. More than twofold variance in ejection fraction (EF%), fractional shortening (FS%), left ventricular volumes (LVVols), internal dimensions (LVIDs), mass (LVM), and posterior wall (LVPW) thickness was found among BXDs. In male BXDs, eQTL mapping identified Ndrg4 on chromosome 8 QTL to be positively correlated with LVVol and LVID and negatively associated with cardiomyocyte diameter. In female BXDs, significant QTLs were found on chromosomes 7 and 3 to be associated with LVPW and EF% and FS%, respectively, and Josd2, Dap3, and Tpm3 were predicted as strong candidate genes. Our study found variable cardiovascular traits among BXD strains and identified multiple associated QTLs, suggesting an influence of genetic background on expression of echocardiographic and cardiomyocyte diameter traits. Increased LVVol and reduced EF% and FS% represented dilated cardiomyopathy, whereas increased LV mass and wall thickness indicated hypertrophic cardiomyopathy traits. The BXD family is ideal for identifying candidate genes, causal and modifier, that influence cardiovascular phenotypes.NEW & NOTEWORTHY This study aimed to establish a cardiac phenotype-genotype correlation in murine genetic reference population of BXD RI strains by phenotyping the echocardiography, blood pressure, and cardiomyocyte diameter traits and associating each collected phenotype with genetic background. Our study identified several QTLs and candidate genes that have significant association with cardiac hypertrophy, ventricular dilation, and function including systolic hyperfunction and dysfunction.
摘要：
背景：重组近交系BXD小鼠的遗传参考群体来自C57BL/6J和DBA/2J菌株之间的杂交。DBA/2J亲本表现出心肌病表型，而C57BL/6J心脏正常.对BXD小鼠进行测序以研究心肌病中的遗传相互作用。
目的：该研究旨在评估BXDs的心肌病性状，并研究这些性状的数量遗传结构。
方法：超声心动图，血压,在4-5月龄时，从44株BXD家族（N>5/性别）获得的心肌细胞大小参数与心脏转录组相关，并进行表达数量性状基因座（eQTL）定位。
结果：射血分数方差超过2倍（EF％），分数缩短(FS%)，左心室容积（LVVol），内部尺寸(LVID),质量(LVM)，在BXDs中发现后壁（LVPW）厚度。在男性BXD中，eQTL定位鉴定8号染色体QTL上的Ndrg4与LVVol和LVID呈正相关，与心肌细胞直径呈负相关。在女性BXD中，在7号和3号染色体上发现显著的eQTL与LVPW和EF%和FS%相关，分别,Josd2、Dap3和Tmp3被预测为强候选基因。
结论：我们的研究发现了BXD菌株中不同的心血管特征，并确定了多个相关的QTL，提示遗传背景对超声心动图和心肌细胞直径性状表达的影响。LVVol升高和EF%和FS%降低代表扩张型心肌病，而左心室质量和壁厚增加表明肥厚型心肌病的特征。BXD家族是鉴定候选基因的理想选择,因果和修饰语，影响心血管表型。
目的：该研究旨在评估BXDs的心肌病性状，并研究这些性状的数量遗传结构。
方法：超声心动图，血压,在4-5月龄时，从44株BXD家族（N>5/性别）获得的心肌细胞大小参数与心脏转录组相关，并进行表达数量性状基因座（eQTL）定位。
结果：射血分数方差超过2倍（EF％），分数缩短(FS%)，左心室容积（LVVol），内部尺寸(LVID),质量(LVM)，在BXDs中发现后壁（LVPW）厚度。在男性BXD中，eQTL定位鉴定8号染色体QTL上的Ndrg4与LVVol和LVID呈正相关，与心肌细胞直径呈负相关。在女性BXD中，在7号和3号染色体上发现显著的eQTL与LVPW和EF%和FS%相关，分别,Josd2、Dap3和Tmp3被预测为强候选基因。
结论：我们的研究发现了BXD菌株中不同的心血管特征，并确定了多个相关的QTL，提示遗传背景对超声心动图和心肌细胞直径性状表达的影响。LVVol升高和EF%和FS%降低代表扩张型心肌病，而左心室质量和壁厚增加表明肥厚型心肌病的特征。BXD家族是鉴定候选基因的理想选择,因果和修饰语，影响心血管表型。
