Genetic analysis of blood pressure in C3H/HeJ and SWR/J mice
Genetic analysis of blood pressure in C3H/HeJ and SWR/J mice
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DOI：
10.1152/physiolgenomics.00212.2003
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发表时间：
2004-04-13
影响因子：
4.6
通讯作者：
Paigen, B
中科院分区：
文献类型：
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作者：
DiPetrillo, K;Tsaih, SW;Paigen, B
高血压是由多种环境和遗传因素引起的复杂表型。数量性状基因座（QTL）分析是鉴定复杂疾病基因组区域的有效方法。我们使用217个来自血压正常的C3 H/HeJ和高血压的SWR/J近交系之间的杂交的F-2后代（雄性和雌性）进行了小鼠血压的QTL分析。我们的分析在染色体1 [Chr 1; Bpq 8;峰值78 cM; 95%置信区间64-106 cM;比值比（LOD）的对数3.5;峰值标记D1 Mit 105]和染色体16 [Bpq 9;峰值56 cM; 95%置信区间46-58 cM; LOD 3.6;峰值标记D16 Mit 158]上鉴定了控制血压的显著QTL。先前在C57 BL/6 J和A/J小鼠之间的杂交中鉴定了Bpq 8，并且我们通过组合来自这些杂交的数据将该QTL从42 cM缩小到18 cM（95%置信区间68-86 cM）。通过检查Bpq 8中祖先等位基因在高等位基因株系（C57 BL/6 J，SWR/J）中保守而与低等位基因株系（A/J，C3 H/HeJ）不同的区域，我们确定了一个2.3-cM区域，其中高等位基因株系共享一个共同的单倍型。Bpq 8与大鼠和人类已知的QTL一致，表明Bpq 8的致病基因可能是人类高血压的保守致病基因。
Hypertension is a complex phenotype induced by multiple environmental and genetic factors. Quantitative trait locus (QTL) analysis is a powerful method for identifying genomic regions underlying complex diseases. We conducted a QTL analysis of blood pressure in mice using 217 F-2 progeny (males and females) from a cross between the normotensive C3H/HeJ and hypertensive SWR/J inbred strains. Our analysis identified significant QTL controlling blood pressure on chromosome 1 [Chr 1; Bpq8; peak 78 cM; 95% confidence interval 64-106 cM; logarithm of the odds ratio (LOD) 3.5; peak marker D1Mit105] and on Chr 16 (Bpq9; peak 56 cM; 95% confidence interval 46-58 cM; LOD 3.6; peak marker D16Mit158). Bpq8 was previously identified in a cross between C57BL/6J and A/J mice, and we narrowed this QTL from 42 to 18 cM (95% confidence interval 68-86 cM) by combining the data from these crosses. By examining Bpq8 for regions where ancestral alleles were conserved among the high allele strains (C57BL/6J, SWR/J) and different from the low allele strains (A/J, C3H/HeJ), we identified a 2.3-cM region where the high allele strains shared a common haplotype. Bpq8 is concordant with known QTL in both rat and human, suggesting that the causal gene underlying Bpq8 may be conserved as a disease gene in human hypertension.