Chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.
Chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.
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18 号染色体和 X 号染色体是大鼠肾病范围蛋白尿的数量性状基因座。
DOI：
10.1007/s00467-005-2020-8
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Kohane,IsaacS
中科院分区：
文献类型：
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作者：
Schachter,AsherD;Ichimura,Takaharu;Kohane,IsaacS
人们已经研究了许多细胞和分子扰动，以阐明肾病范围蛋白尿的致病机制，这可能反过来揭示疾病特异性机制。我们分析了 PhysGen 部分大鼠组的公开数据，以确定是否存在与肾病范围蛋白尿相关的数量性状位点。截至撰写本文时，基因组应用程序已针对 22 条大鼠染色体中的 15 条，培育出接受肾脏方案的康体大鼠品系，主要以 Brown-Norway (BN) 和 Dahl 盐敏感 (SS) 品系为亲本。我们将感兴趣的染色体定义为共体 SS-xBN 菌株，其表型测量结果与 SS 显着不同，但与 BN 菌株没有显着差异，按性别分层。我们根据相关菌株肾组织中的功能对差异表达基因进行过滤和聚类。男性 SS 的蛋白尿显着高于男性 SS-18BN，男性 SS 的蛋白尿显着高于女性 SS。差异表达基因的功能聚类产生了两个特定的功能聚类：细胞凋亡（p=0.022）和血管生成（p=0.046）。基因表达谱显示凋亡基因和血管生成基因的差异表达。然而，肾组织的TUNEL染色显示凋亡核的数量没有显着差异。我们得出结论，18 号染色体和 X 号染色体是大鼠肾病范围蛋白尿的数量性状位点。
Numerous cellular and molecular perturbations have been studied to elucidate the pathogenic mechanisms underlying nephrotic-range proteinuria, which may in turn shed light on disease-specific mechanisms. We have analyzed the publicly available data from the PhysGen partial panel of consomic rats to determine whether there are quantitative trait loci that associate with nephrotic-range proteinuria. As of this writing, consomic rat strains subjected to the renal protocol have been bred by the Program for Genomic Applications for 15 of the 22 rat chromosomes for both genders, predominantly with the Brown–Norway (BN) and Dahl salt-sensitive (SS) strains as parents. We defined chromosomes of interest as consomic SS-xBN strains whose phenotype measurements differed significantly from SS but not BN strains, stratified by gender. We filtered and clustered differentially expressed genes by function in renal tissue from relevant strains. Proteinuria was significantly higher in male SS vs. male SS-18BN, and it was significantly higher in male SS vs. female SS. Functional clustering of differentially expressed genes yielded two specific functional clusters: apoptosis (p=0.022) and angiogenesis (p=0.046). Gene expression profiles demonstrated differential expression of apoptotic and angiogenic genes. However, TUNEL stains of renal tissue showed no significant difference in the number of apoptotic nuclei. We conclude that chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.