Dietz, H. C. | bioRxiv Science

bioRxiv2019

Targetable cellular signaling events drive arterial rupture in knock-in mouse models of vascular Ehlers-Danlos Syndrome

Introduction Introduction Main Methods Author contributions Competing Interests Data availability References Vascular Ehlers-Danlos Syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene1. Currently, loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including spontaneous arterial dissection and/or rupture, the major cause of mortality2-4.\n\nUsing novel mouse models of vEDS that carry heterozygous Col3a1 glycine substitutions, we show that signaling abnormalities in the PLC/IP3/PKC/ERK pathway (Phospholipase C/Inositol 1,4,5-triphosphate/Protein Kinase C/Extrace ...

genetics↗

bioRxiv2019

A positively selected, common, missense variant in FBN1 confers a 2.2 centimeter reduction of height in the Peruvian population

Peruvians are among the shortest people in the world. To understand the genetic basis of short stature in Peru, we examined an ethnically diverse group of Peruvians and identified a novel, population-specific, missense variant in FBN1 (E1297G) that is significantly associated with lower height in the Peruvian population. Each copy of the minor allele (frequency = 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). This is the largest effect size known for a common height-associated variant. This variant shows strong evidence of positive selection within the Peruvian population and is significantly more frequent in Native American populations from coastal regions of Peru compared to populations from the Andes or the Amazon, suggesting that short stature in Peruvians is the result of adaptation to the coastal environment. One Sentence SummaryA mutation found in Peruvians has the largest known effect on height for a common variant. This variant is specific to Native American ancestry.

genomics↗