Genome-wide searches for blood pressure quantitative trait loci in the stroke-prone spontaneously hypertensive rat of a Japanese colony
Genome-wide searches for blood pressure quantitative trait loci in the stroke-prone spontaneously hypertensive rat of a Japanese colony
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DOI：
10.1097/00004872-200302000-00020
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发表时间：
2003-02-01
影响因子：
4.9
通讯作者：
Yamori, Y
中科院分区：
文献类型：
--
作者：
Kato, N;Mashimo, T;Yamori, Y
目的在易卒中型自发性高血压大鼠（stroke-prone spontaneous hypertensive rats，SHRSP）中发现了多个血压数量性状基因座，但不同杂交组合间的结果并不一致。为了评估潜在的混杂因素在连锁分析中，我们进行了全基因组筛选的F-2人口来自SHRSP和Wistar-Kyoto大鼠的日本colony.Methods两个F-2队列独立产生：F-2-1（1110名男性和110名女性大鼠），和F-2-2（1174名男性和184名女性大鼠）。在F-2-1中纵向测量血压（从2至5月龄和盐负荷后1个月），而在F2-2中在13周龄时测量血压。随后的初步筛选与251标记在F-2-1雄性后代，170标记被选中，其特征在于在其余population.Results当578只大鼠一起分析，标记从5个染色体区域显示显着的连锁血压在13周龄。在大鼠1号染色体上发现了最强和最一致的连锁（最大对数的比值分数达到8.3）。在其他区域，两性之间的联系程度更为突出。一些证据的年龄特异性和性别特异性的连锁被检测到在5个额外的区域在F-2-1队列在日本殖民地，但是，有没有显着的连锁到几个染色体区域以前报道在其他SHRSP colonization.Conclusions我们的数据提供了坚实的证据，染色体-1连锁，并证明了老龄化，性别和饮食操纵的重要性连锁分析。此外，在寻找血压数量性状基因座时，亲本大鼠品系的组合似乎是至关重要的。J Hypertens 21：295-303（C）2003 Lippincott威廉姆斯威尔金斯。
Objectives Although several quantitative trait loci for blood pressure have been reported in stroke-prone spontaneously hypertensive rats (SHRSP), the results are not always concordant among different crosses. To evaluate potential confounding factors in linkage analysis, we performed genome-wide screens in F-2 populations derived from SHRSP and Wistar-Kyoto rats of a Japanese colony.Methods Two F-2 cohorts were independently produced: F-2-1 (1110 male and 110 female rats), and F-2-2 (1174 male and 184 female rats). Blood pressure was measured longitudinally (from 2 to 5 months of age and 1 month after salt-loading) in F-2-1, while it was measured at 13 weeks of age in F2-2. Subsequent to an initial screen with 251 markers in F-2-1 male progeny, 170 markers were selected and characterized in the remaining populations.Results When 578 rats were analyzed together, markers from five chromosomal regions showed significant linkage to blood pressure at 13 weeks of age. The strongest and the most consistent linkage was found on rat chromosome 1 (a maximal log of the odds score reached 8.3). In the other regions, the degree of linkage was more prominent in either of sexes. Some evidence of age-specific and sex-specific linkage was detected in five additional regions in the F-2-1 cohort In the Japanese colony, however, there was no significant linkage to several chromosomal regions previously reported in other SHRSP colonies.Conclusions Our data provide solid evidence of a chromosome-1 linkage and demonstrate the importance of aging, sex, and dietary manipulation in linkage analysis. Also, the combination of parental rat strains seems to be critical when searching for blood pressure quantitative trait loci. J Hypertens 21:295-303 (C) 2003 Lippincott Williams Wilkins.