Abstract
Collaterals are arteriole‐to‐arteriole anastomoses that connect adjacent arterial trees. They lessen the severity of ischemic tissue injury by serving as endogenous bypass vessels when one tree becomes occluded. We previously found remarkably wide variation in native collateral number and diameter in inbred mouse strains. These findings suggest that a significant genetic component underlies formation of the native collateral circulation. Here we sought to identify candidate genes and their polymorphisms responsible for this wide variation. To explore the underlying genetic architecture, we created 221 F2 mice intercrossed between C57BL/6J and BALB/cByJ and performed linkage analyses to identify quantitative trait loci (QTL) for native collateral number and diameter. These same traits were quantified in 15 inbred strains with 10 mice from each to permit haplotype association mapping. Our results suggest that collateral number is governed by 4 QTL, including an epistasis between the loci on chromosomes 1 and 3 and collateral diameter by one identical QTL. This common QTL, possessing a large genetic effect (above 30%), is on chromosome 7. Association mapping pinpointed a 172k bp region with high p value (p = 2.2 × E10−5) and 2 candidate genes. We conclude that number and diameter of native collaterals are highly heritable complex traits with one QTL predominantly affecting their variation.
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