The ovine MHC class IIa is known to consist of six to eight loci located in close proximity on chromosome 20, forming haplotypes that are typically inherited without recombination. Here, we characterise the class IIa haplotypes within the Soay sheep (Ovis aries) on St. Kilda to assess the diversity present within this unmanaged island population. We used a stepwise sequence-based genotyping strategy to identify alleles at seven polymorphic MHC class IIa loci in a sample of 118 Soay sheep from four cohorts spanning 15 years of the long-term study on St. Kilda. DRB1, the most polymorphic MHC class II locus, was characterised first in all 118 sheep and identified six alleles. Using DRB1 homozygous animals, the DQA (DQA1, DQA2 and DQA2-like) and DQB (DQB1, DQB2 and DQB2-like) loci were sequenced, revealing eight haplotypes. Both DQ1/DQ2 and DQ2/DQ2-like haplotype configurations were identified and a single haplotype carrying three DQB alleles. A test sample of 94 further individuals typed at the DRB1 and DQA loci found no exceptions to the eight identified haplotypes and a haplotype homozygosity of 21.3%. We found evidence of historic positive selection at DRB1, DQA and DQB. The limited variation at MHC class IIa loci in Soay sheep enabled haplotype characterisation but showed that no single locus could capture the full extent of the expressed variation in the region.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525122 | PMC |
http://dx.doi.org/10.1007/s00251-019-01109-w | DOI Listing |
Neuropharmacology
January 2025
Department of Anatomy & Neuroscience, School of Medicine, University College Cork (UCC), Cork, Ireland; APC Microbiome Ireland, UCC, Cork, Ireland. Electronic address:
Degeneration of midbrain nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). Peripheral delivery of a compound(s) to arrest or slow this dopaminergic degeneration is a key therapeutic goal. Pan-inhibitors of histone deacetylase (HDAC) enzymes, key epigenetic regulators, have shown therapeutic promise in PD models.
View Article and Find Full Text PDFJ Virol
January 2025
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou University, Lanzhou, China.
Lumpy skin disease virus (LSDV) infection poses a significant threat to global cattle farming. Currently, effective therapeutic agents are lacking. TMP269, a small molecule inhibitor of class IIa histone deacetylase inhibitor, plays a vital role in cancer therapy.
View Article and Find Full Text PDFEur J Clin Invest
January 2025
Department of Surgical, Medical and Molecular Pathology and Critical Area, Laboratory of Biochemistry, University of Pisa, Pisa, Italy.
Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2.
View Article and Find Full Text PDFPharmacol Res Perspect
February 2025
New Drug Development Center, Daegu, Korea.
Oxidation of dopamine can cause various side effects, which ultimately leads to cell death and contributes to Parkinson's disease (PD). To counteract dopamine oxidation, newly synthesized dopamine is quickly transported into vesicles via vesicular monoamine transporter 2 (VMAT2) for storage. VMAT2 expression is reduced in patients with PD, and studies have shown increased accumulation of dopamine oxidation byproducts and α-synuclein in animals with low VMAT2 expression.
View Article and Find Full Text PDFMol Neurodegener
January 2025
College of Life Sciences and Oceanography, Brain Disease and Big Data Research Institute, Shenzhen University, Shenzhen, 518060, Guangdong, China.
Background: Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!