{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang S"],"funding":["NHLBI NIH HHS"],"pagination":["558-68"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2924933"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["107(4)"],"pubmed_abstract":["<h4>Rationale</h4>Collaterals are arteriole-to-arteriole anastomoses that connect adjacent arterial trees. They lessen ischemic tissue injury by serving as endogenous bypass vessels when the trunk of 1 tree becomes narrowed by vascular disease. The number and diameter (\"extent\") of native (preexisting) collaterals, plus their amount of lumen enlargement (growth/remodeling) in occlusive disease, show remarkably wide variation among inbred mouse strains (eg, C57BL/6 and BALB/c), resulting in large differences in tissue injury in models of occlusive disease. Evidence suggests similar large differences exist among healthy humans.<h4>Objective</h4>To identify candidate loci responsible for genetic-dependent collateral variation.<h4>Methods and results</h4>Cerebral collateral number and diameter were determined in 221 C57BL/6xBALB/c F2 progeny, followed by linkage analysis to identify quantitative trait loci (QTL) for collateral number and diameter. Four QTL were obtained for collateral number, including epistasis between 2 loci. A QTL that was identical to the strongest QTL for collateral number on chromosome 7 (logarithm of the odds [LOD]=29, effect size=37%) was also mapped for collateral diameter (LOD=17, effect size=30%). Chromosome substitution strain analysis confirmed this locus. We also obtained a unique QTL on chromosome 11 for collateral remodeling after middle cerebral artery occlusion. Association mapping within the chromosome 7 QTL interval using collateral traits measured for 15 inbred strains delineated 172-kbp (P=0.00002) and 290-kbp (P=0.0004) regions on chromosome 7 containing 2 and 7 candidate genes, respectively.<h4>Conclusions</h4>We conclude that collateral extent and remodeling are unique, highly heritable complex traits, with 1 QTL predominantly affecting native collateral number and diameter."],"journal":["Circulation research"],"pubmed_title":["Genetic architecture underlying variation in extent and remodeling of the collateral circulation."],"pmcid":["PMC2924933"],"funding_grant_id":["HL62584","R01 HL090655-03","HL090655","R01 HL090655","T32 HL083828","R01 HL062584"],"pubmed_authors":["Sealock R","Wang S","Zhang H","Faber JE","Dai X"],"additional_accession":[]},"is_claimable":false,"name":"Genetic architecture underlying variation in extent and remodeling of the collateral circulation.","description":"<h4>Rationale</h4>Collaterals are arteriole-to-arteriole anastomoses that connect adjacent arterial trees. They lessen ischemic tissue injury by serving as endogenous bypass vessels when the trunk of 1 tree becomes narrowed by vascular disease. The number and diameter (\"extent\") of native (preexisting) collaterals, plus their amount of lumen enlargement (growth/remodeling) in occlusive disease, show remarkably wide variation among inbred mouse strains (eg, C57BL/6 and BALB/c), resulting in large differences in tissue injury in models of occlusive disease. Evidence suggests similar large differences exist among healthy humans.<h4>Objective</h4>To identify candidate loci responsible for genetic-dependent collateral variation.<h4>Methods and results</h4>Cerebral collateral number and diameter were determined in 221 C57BL/6xBALB/c F2 progeny, followed by linkage analysis to identify quantitative trait loci (QTL) for collateral number and diameter. Four QTL were obtained for collateral number, including epistasis between 2 loci. A QTL that was identical to the strongest QTL for collateral number on chromosome 7 (logarithm of the odds [LOD]=29, effect size=37%) was also mapped for collateral diameter (LOD=17, effect size=30%). Chromosome substitution strain analysis confirmed this locus. We also obtained a unique QTL on chromosome 11 for collateral remodeling after middle cerebral artery occlusion. Association mapping within the chromosome 7 QTL interval using collateral traits measured for 15 inbred strains delineated 172-kbp (P=0.00002) and 290-kbp (P=0.0004) regions on chromosome 7 containing 2 and 7 candidate genes, respectively.<h4>Conclusions</h4>We conclude that collateral extent and remodeling are unique, highly heritable complex traits, with 1 QTL predominantly affecting native collateral number and diameter.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Aug","modification":"2024-11-12T20:06:59.776Z","creation":"2019-03-26T23:49:18Z"},"accession":"S-EPMC2924933","cross_references":{"pubmed":["20576932"],"doi":["10.1161/CIRCRESAHA.110.224634","10.1161/circresaha.110.224634"]}}