DiPetrillo Keith, Tsaih Shirng-Wern, Sheehan Susan, Johns Conrado, Kelmenson Peter, Gavras Haralambos, Churchill Gary A, Paigen Beverly
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Physiol Genomics. 2004 Apr 13;17(2):215-20. doi: 10.1152/physiolgenomics.00212.2003.
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.
高血压是一种由多种环境和遗传因素诱发的复杂表型。数量性状基因座（QTL）分析是识别复杂疾病潜在基因组区域的有效方法。我们利用来自正常血压的C3H/HeJ和高血压的SWR/J近交系杂交产生的217只F(2)后代（雄性和雌性）小鼠进行了血压的QTL分析。我们的分析在1号染色体[Chr 1；Bpq8；峰值78 cM；95%置信区间64 - 106 cM；优势对数比（LOD）3.5；峰值标记D1Mit105]和16号染色体（Bpq9；峰值56 cM；95%置信区间46 - 58 cM；LOD 3.6；峰值标记D16Mit158）上鉴定出了控制血压的显著QTL。Bpq8先前在C57BL/6J和A/J小鼠的杂交后代中被鉴定出来，通过合并这些杂交的数据，我们将这个QTL从42 cM缩小到了18 cM（95%置信区间68 - 86 cM）。通过检查Bpq8中高等位基因品系（C57BL/6J、SWR/J）中祖先等位基因保守且与低等位基因品系（A/J、C3H/HeJ）不同的区域，我们确定了一个2.3 - cM的区域，高等位基因品系在该区域共享一个共同单倍型。Bpq8与大鼠和人类中已知的QTL一致，这表明Bpq8潜在的致病基因可能作为人类高血压的致病基因而被保留。
