Comparative genomic characterization of indigenous fat-tailed Akkaraman sheep with local and transboundary sheep breeds

The domestic sheep with over 1200 breeds descended from those early domesticated animals that are bred for a variety of resources such as meat, milk and wool. Akkaraman, a fat-tailed indigenous sheep breed of Turkiye, is widespread throughout Central Anatolia, with the largest indigenous sheep population. Assessing the genetic diversity and genomic structure of animal breeds is among the key contributors to deciphering adaptation to environmental extremes and constructing efficient genetic improvement strategies. Therefore, this study aimed to characterize the genome of Akkaraman breed against various world-renowned transboundary sheep and indigenous sheep with fat and thin tails. Genetic similarities and differences between those breeds have been displayed by estimating and comparing various genetic diversity indices, linkage disequilibrium (LD) estimates and fixation index (FST), runs of homozygosity (ROH) as well as PCA and neighbour-joining tree analysis. Akkaraman sheep were observed to form a cluster alongside Moghani, Karakas, Tibetan and Cyprus Fat Tail sheep, which are primarily the sole representatives of fat-tailed sheep in the study. This clustering was evident in both the PCA and neighbour-joining tree analysis. The Akkaraman sheep was also observed to have the lowest genomic inbreeding and one of the lowest numbers of ROHs, which might also indicate that the breed has not been exposed to historical intensive selection pressure, inbred mating or a massive population bottleneck that might leave strong marks of genomic homozygosity. The results improve our understanding of the genetic diversity in Akkaraman sheep in comparison with certain mainstream sheep breeds as well as those indigenous breeds from around the world. Additionally, findings will also provide valuable insights to perform further GWAS effectively by considering population structure, diversity and LD patterns observed among the breeds while providing practical knowledge that will contribute to designing efficient and successful genome-based selection programmes for worldwide sheep production systems

Genome-Wide Scan of Wool Production Traits in Akkaraman Sheep

The objective of this study was to uncover the genetic background of wool quality, a production trait, by estimating genomic heritability and implementing GWAS in Akkaraman sheep. The wool characteristics measured included fibre diameter (FD) and staple length (SL) at the age of 8 months and yearling fibre diameter (YFD), yearling staple length (YSL) and yearling greasy fleece weight (YGFW) at 18 months of age. Animals were genotyped using the Axiom 50 K Ovine Genotyping Array. Maximum likelihood estimations of a linear mixed model (LMM) were used to estimate genomic heritability, where GWAS was conducted following a score test of each trait. Genomic heritability estimates for the traits ranged between 0.22 and 0.63, indicating that phenotypes have a moderate range of heritability. One genome- and six chromosome-wide significant SNPs were associated with the wool traits in Akkaraman lambs. Accordingly, TRIM2, MND1, TLR2, RNF175, CEP290, TMTC3, RERE, SLC45A1, SOX2, MORN1, SKI, FAAP20, PRKCZ, GABRD, CFAP74, CALML6 and TMEM52 genes as well as nine uncharacterized regions (LOC101118971, LOC105609137, LOC105603067, LOC101122892, LOC106991694, LOC106991467, LOC106991455, LOC105616534 and LOC105609719) were defined as plausible candidates. The findings of this study shed light on the genetics of wool quality and yield for the Akkaraman breed and suggests targets for breeders during systematic breeding programmes

CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma

Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study we investigated whether the degree of vascularity correlated with prognosis in a large cohort of pHGG (n = 150) and whether different vessel markers carried different prognostic value. We found that CD105 (endoglin) had a strongly significant association with poor prognosis on multivariate analysis (p = <0.001). Supervised hierarchical clustering of genome wide gene expression data identified 13 genes associated with differential degrees of vascularity in the cohort. The novel angiogenesis-associated genes identified in this analysis (including MIPOL-1 and ENPP5) were validated by realtime polymerase chain reaction. We also demonstrate that CD105 positive blood vessels associate with CD133 positive tumour cells and that a proportion of CD105 positive vessel cells demonstrates co-positivity for CD133, suggesting that the recently described phenomenon of vasculogenic mimicry occurs in pHGG. Together, the data suggest that targeting angiogenesis, and in particular CD105, is a valid therapeutic strategy for pHGG

Early onset Alzheimer's disease

WOS: 000209194000108

Cognitive impairment in general paresis: AD-like pattern?

16th Congress of the European-Federation-of-Neurological-Societies (EFNS) -- SEP 08-11, 2012 -- Stockholm, SWEDENWOS: 000309359700206…European Federat Neurol Soc (EFNS