genetic dissection of the canq1 locus governing variation in extent of the collateral circulation的遗传解剖canq1轨迹管理侧枝循环的变化程度.pdfVIP

Genetic Dissection of the Canq1 Locus Governing Variation in Extent of the Collateral Circulation 1,3 1,3 2 1,3 1,3 Shiliang Wang , Hua Zhang , Tim Wiltshire , Robert Sealock , James E. Faber * 1 Department of Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America Abstract Background.: Native (pre-existing) collaterals are arteriole-to-arteriole anastomoses that interconnect adjacent arterial trees and serve as endogenous bypass vessels that limit tissue injury in ischemic stroke, myocardial infarction, coronary and peripheral artery disease. Their extent (number and diameter) varies widely among mouse strains and healthy humans. We previously identified a major quantitative trait locus on chromosome 7 (Canq1, LOD = 29) responsible for 37% of the heritable variation in collateral extent between C57BL/6 and BALB/c mice. We sought to identify candidate genes in Canq1 responsible for collateral variation in the cerebral pial circulation, a tissue whose strain-dependent variation is shared by similar variation in other tissues. Methods and Findings: Collateral extent was intermediate in a recombinant inbred line that splits Canq1 between the C57BL/6 and BALB/c strains. Phenotyping and SNP-mapping of an expanded panel of twenty-one informative inbred strains narrowed the Canq1 locus, and genome-wide linkage analysis of a SWRxSJL-F2 cross confirmed its