Genetic Mapping of Soluble Guanylyl Cyclase Genes

Author:

Azam Mohammad1,Gupta Gopa1,Chen Wei1,Wellington Sandra1,Warburton Dorothy1,Danziger Robert S.1

Affiliation:

1. From the Department of Internal Medicine (M.A., G.G., W.C., R.S.D.) and Departments of Genetics and Development and Pediatrics (S.W., D.W.), Columbia University, New York, NY. Dr Azam is currently at ExpressGen Inc, Chicago, Ill.

Abstract

Abstract —The nitric oxide (NO) signaling system, consisting of NO synthases, soluble guanylyl cyclase, and cGMP, plays a prominent role in salt handling and regulation of blood pressure. Soluble guanylyl cyclases are heme-containing heterodimers (α/β). The α1/β1 isoform has greater NO sensitivity than the α1/β2. It has recently been shown that expression of the β subunits is altered in the kidney of the Dahl salt-sensitive rat, ie, the β1 subunit is decreased and the β2 subunit increased. However, whether soluble guanylyl cyclase is linked to salt sensitivity is not known. In the present study, we investigated linkage of guanylyl cyclase genes to blood pressure. α1 and β1 gene loci for soluble guanylyl cyclase were mapped to rat chromosome 2, and the β2 gene locus was mapped to rat chromosome 5 using fluorescent in situ metaphase hybridization. By use of a rat radiation hybrid panel, the gene loci were then further mapped with respect to known quantitative trait locus markers of salt-sensitive hypertension in the Dahl rat on chromosomes 2 and 5. Genes for α1 and β1 were closely linked by two-point analysis to Na + ,K + -ATPase α1 isoform (LOD of 15.1 and 14.0, respectively) and calmodulin-dependent protein kinase II-δ loci (LOD of 14.3 and 12.9, respectively), which have been previously shown to flank a quantitative trait locus for blood pressure in the Dahl rat. The α1 and β1 genes were closely linked (LOD of 11.3; θ, 0.4). The β2 gene locus was closely linked to the endothelin-2 (ET-2) locus (LOD of 13.0), which has been shown to cosegregate with blood pressure. We conclude that soluble guanylyl cyclase subunit loci, ie, α1, β1, and β2, are good candidates for genes controlling salt-sensitive hypertension in the Dahl rat.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

Cited by 28 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3