Mutational and phenotypic characterisation of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Care delivery for HHT patients is impeded by the need for laborious, repeated phenotyping and gaps in knowledge regarding the relationships between causal DNA variants in ENG, ACVRL1, SMAD4 and GDF2, and clinical manifestations. To address this, we analyzed DNA samples from 183 previously uncharacterized, unrelated HHT and suspected HHT cases using the ThromboGenomics high-throughput sequencing platform. We identified 127 rare variants across 168 heterozygous genotypes. Applying modified American College of Medical Genetics and Genomics Guidelines, 106 variants were classified as pathogenic/likely pathogenic and 21 as nonpathogenic (variant of uncertain significance/benign). Unlike the protein products of ACVRL1 and SMAD4, the extracellular ENG amino acids are not strongly conserved. Our inferences of the functional consequences of causal variants in ENG were therefore informed by the crystal structure of endoglin. We then compared the accuracy of predictions of the causal gene blinded to the genetic data using 2 approaches: subjective clinical predictions and statistical predictions based on 8 Human Phenotype Ontology terms. Both approaches had some predictive power, but they were insufficiently accurate to be used clinically, without genetic testing. The distributions of red cell indices differed by causal gene but not sufficiently for clinical use in isolation from genetic data. We conclude that parallel sequencing of the 4 known HHT genes, multidisciplinary team review of variant calls in the context of detailed clinical information, and statistical and structural modeling improve the prognostication and treatment of HHT

Natural Resources Research Institute Technical Report

The purpose of this project is to determine the regional and local geological, mineralogical, and geochemical factors that control the distribution and grade of the industrial clays in the Minnesota River Valley (MRV) between Redwood Falls and Fairfax, Minnesota and at the Meridian Aggregates Quarry (MAQ), St. Cloud, Minnesota. These controlling factors fall into three broad categories: 1) bedrock controls - parent rock characteristics; 2) physical controls - faults, paleotopography, etc.; and 3) chemical controls.Funded by the Minerals Coordinating Committee through the Minerals Diversification Plan; University of Minnesota Duluth, Natural Resources Research Institute, 5013 Miller Trunk Highway, Duluth, MN 5581

Résistance à l'infection par Salmonella abortusovis : existe-t-il un équivalent du gène Ity chez les ovins ?

International audienc