A Non-Synonymous HMGA2 Variant Decreases Height in Shetland Ponies and Other Small Horses

The identification of quantitative trait loci (QTL) such as height and their underlying causative variants is still challenging and often requires large sample sizes. In humans hundreds of loci with small effects control the heritable portion of height variability. In domestic animals, typically only a few loci with comparatively large effects explain a major fraction of the heritability. We investigated height at withers in Shetland ponies and mapped a QTL to ECA 6 by genome-wide association (GWAS) using a small cohort of only 48 animals and the Illumina equine SNP70 BeadChip. Fine-mapping revealed a shared haplotype block of 793 kb in small Shetland ponies. The HMGA2 gene, known to be associated with height in horses and many other species, was located in the associated haplotype. After closing a gap in the equine reference genome we identified a non-synonymous variant in the first exon of HMGA2 in small Shetland ponies. The variant was predicted to affect the functionally important first AT-hook DNA binding domain of the HMGA2 protein (c.83G>A; p.G28E). We assessed the functional impact and found impaired DNA binding of a peptide with the mutant sequence in an electrophoretic mobility shift assay. This suggests that the HMGA2 variant also affects DNA binding in vivo and thus leads to reduced growth and a smaller stature in Shetland ponies. The identified HMGA2 variant also segregates in several other pony breeds but was not found in regular-sized horse breeds. We therefore conclude that we identified a quantitative trait nucleotide for height in horses.     

Activity of Mg2+-ATPase and cytochrome c-Oxidase in microsporocytes and anther wall during microsporogenesis inLarix europaea D.C.

Studies have been made on the activity of two mitochondrial enzymes, Mg²⁺ ATPase (E.C.3.6.1.3.) and cytochrome c-oxidase (E.C.I.9.3.2.) in microsporocytes and somatic cells of anther in larch. The material for study were homogeneous fractions of microsporocytes from 15 stages of meiosis and the attendant anther somatic cells. The results have demonstrated that cells undergoing meiosis exhibit considerable mitochondrial metabolic activity. It is characterized by considerable variations in the activity level of both enzymes studied. The level and dynamics of variations of Mg²⁺-ATPase and cytochrome c-oxidase activity in microsporocytes are clearly different from those in the anther somatic cells. The cytochrome c-oxidase activity in microsporocytes throughout microsporogenesis is higher compared with that in the anther wall cells, whereas the Mg²⁺-ATPase activity in microsporocytes averagesca. one half that in the anther somatic cells The dynamics of activity variations of the enzymes under study suggests enhanced mitochondrial metabolism in the period of middle diplotene and young dyad. This result supports the thesis following from our earlier studies that the middle diplotene and young dyad constitute specific metabolic switches in microsporogenesis in larch.     

Immunochemical and biological studies of antigens isolated from a strain of Bacteroides fragilis

Phenol/water-extracted lipopolysaccharide and a fraction HM, extracted with acetate buffer pH 2.0, from Bacteroides fragilis strain 62/73 are antigenically different as shown by immunodiffusion, passive haemagglutination, haemagglutination inhibition and preliminary chemical investigations. Biological activity, assessed with the local Shwartzmann reaction, was demonstrated for the lipopolysaccharide whereas antigen HM was almost inactive in this test. HM is immunogenic in rabbits. Antibodies against HM were detected in seven out of ten sera of healthy humans.     

Familial translocation t(1p-;21q+) associated with Down's syndrome

Summary Familial occurrence of 1/21 translocation in connection with trisomy 21 was described. The possibilities of inheritance of further chromosome rearrangements arising during the gametogenesis of persons with this translocation were considered.     

Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome

Background: Ehlers-Danlos syndrome (EDS) is a common non-inflammatory, congenital connective tissue disorder. Classical type (cEDS) EDS is one of the more common forms, typically caused by mutations in the COL5A1 and COL5A2 genes, though causative mutations in the COL1A1 gene have also been described. Material and methods: The study group included 59 patients of Polish origin, diagnosed with cEDS. The analysis was performed on genomic DNA (gDNA) with NGS technology, using an Illumina sequencer. Thirty-five genes related to connective tissue were investigated. The pathogenicity of the detected variants was assessed by VarSome. Results: The NGS of 35 genes revealed variants within the COL5A1, COL5A2, COL1A1, and COL1A2 genes for 30 of the 59 patients investigated. Our panel detected no sequence variations for the remaining 29 patients. Discussion: Next-generation sequencing, with an appropriate multigene panel, showed great potential to assist in the diagnosis of EDS and other connective tissue disorders. Our data also show that not all causative genes giving rise to cEDS have been elucidated yet.     

Synthesis,receptor binding studies,optical spectroscopic and in silico structural characterization of morphiceptin analogs with cis‐4‐amino‐L‐proline residues

Three novel morphiceptin analogs, in which Pro in position 2 and/or 4 was replaced by cis‐4‐aminoproline connected with the preceding amino acid through the primary amino group, were synthesized. The opioid receptor affinities, functional assay results, enzymatic degradation studies and experimental and in silico structural analysis of such analogs are presented. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.