Mouse Anti-Chicken Collagen type II Monoclonal antibody, DJJD2

Background: Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-beta inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction. Results: Statistically significant interaction of the CILP rs2073711 T and ASPN D15 alleles with hand OA was observed (OR = 2.48, 95% CI 1.27-4.85, p = 0.008) in a Finnish hand. OA cohort of 543 women (aged. 45-63). When stratified by variation in working tasks, low variation of working tasks increased the risk further (OR = 3.00, 95% CI 1.35-6.66, p = 0. 007). Based on the analysis of ASPN and CILP protein-coding regions, functional studies were performed with one observed variant, rs41278695 in the ASPN 'gene. Analyses showed that bone morphogenetic protein 2 (BMP2) mediated expression of aggrecan (Agc1) and type II collagen (Col2a1) was significantly suppressed (p = 0.011 and p = 0.023, respectively) in a murine chondrocytic cell line (ATDC5) with cells stably expressing ASPN rs41278695. Conclusions: The carriage of either ASPN D15 or CILP rs2073711 TT is associated, with increased risk of symmetrical hand. OA, particularly in individuals with low variation in work tasks. ASPN rs41278695 SNP had an effect on Agc1 and. Col2a1 gene expression when induced with BMP-2 suggesting an effect on the cartilage extracellular matrix composition.

Background: The bulldog calf syndrome is a lethal form of the inherited congenital chondrodysplasias. Among the progeny of the polled Holstein bull Energy P cases of lethal chondrodysplasia were observed. Pedigrees of the cases and the frequency of 3/8 cases among the offspring of Energy P at our teaching and experimental farm Ruthe (LuFG Ruthe) supported the assumption of a germline mutation with a mosaic of normal and defective sperm. Results: All three malformed calves were examined using necropsy, histopathology and computed tomography scanning. The phenotypic appearance of the affected calves was highly similar; they presented with severe disproportionate dwarfism and reduced body weight. The syndrome was characterized by brachygnathia superior, bilateral palatoschisis, shortening and compression of the body due to malformed vertebrae, in their size reduced and malformed ribs and reduced length of the long bones of the limbs. The bones had small irregular diaphyses and enlarged epiphyses. Whole genome sequencing of one bulldog calf, sperm of its sire Energy P and a normal progeny of Energy P identified a deleterious missense mutation (g.32476082G > A, c. 2986G > A, ss2019324576) within COL2A1 on bovine chromosome (BTA) 5. Sanger sequencing confirmed the ss2019324576 variant in the affected calves and sperm of Energy P. This mutation is located within the collagen triple helix repeat and causes an exchange of glycine to serine (p.996G > S) in COL2A1. This private single nucleotide variant (SNV) was present as a gonadal mosaic in sperm of the bull. All affected calves were in a heterozygous state whereas normal half-siblings and all dams of the progeny from Energy P were missing this SNV. Validation in polled Holstein bulls and normal Holstein calves randomly sampled from several herds and from the LuFG Ruthe confirmed this SNV as private. Conclusions: The identified spontaneous missense mutation within COL2A1 is most likely the cause of lethal chondrodysplasia in the progeny of Energy P through a dominant negative effect. This example suggests that it would be beneficial to conduct whole genome sequencing of sperm from bulls widely used in artificial insemination in order to detect germline mosaicism.