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On average, Peruvian individuals are among the shortest in the world1. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.

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RESUMEN

The microfibril-elastin fiber system, an important constituent of the extracellular matrix, was studied in the rat left atrioventricular valve to investigate the interrelationship of oxytalan, elaunin and elastic fibers in left atrioventricular valve morphology. The elastin fibers forms continuous bundles observed along the length of the valve in atrial and ventricular layers and oriented parallel to endothelium. The elaunin and oxytalan fibers are distributed in the thickest fiber bundles along the length of the valve. The thinner fibers which radiated towards both the atrial and spongiosa layers, either as isolated or arborescent fiber bundles were identified as oxytalan fibers. With transmission electron microscopy elastic fibers were seen mainly in the atrial layer. The spongiosa layer was composed of elaunin and oxytalan fibers and ventricular layer showed elaunin fibers arranged in continuous bundles parallel to the endothelium. Both fibrillin and elastin were seen and identified by immunocytochemistry with colloidal gold in the left atrioventricular valve spongiosa and atrial layers. These observations allow us to suggest that the microfibril-elastin fiber system plays a role in the mechanical protection and maintenance of the integrity of the rat left atrioventricular valve.

Fue estudiado el sistema de fibras microfibrillas-elastina, un componente importante de la matriz extracelular, en la valva atrioventricular izquierda de rata, con la finalidad de investigar la interrelación de oxitalán, elaunin y fibras elásticas en la morfología de dicha valva. Las fibras de elastina forman paquetes continuos a lo largo de la valva en las capas atriales y ventriculares, orientadas paralelamente al endotelio. Las fibras de elaunin y oxitalán se distribuyen en haces de fibras más gruesas a lo largo de la valva. Las fibras más delgadas, las cuales se irradiaban hacia las capas atrial y esponjosa, ya sea como haces de fibras aisladas o arborescentes, fueron identificadas como fibras oxitalán. En la capa atrial a través de microscopía electrónica de transmisión se observaron principalmente fibras elásticas. La capa esponjosa estaba compuesta por fibras de elaunin y oxitalán; la capa ventricular mostró fibras de elaunin dispuestas en haces continuos paralelos al endotelio. Tanto fibrilina y elastina se observaron e identificaron por inmunocitoquímica con oro coloidal en las capas esponjosa y atrial de la valva atrioventricular izquierda. Estas observaciones nos permiten sugerir que el sistema de fibras de elastina-microfibrillas tienen participación en la protección mecánica y la mantención de la integridad de la valva atrioventricular izquierda en la rata.

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