A missense variant in the coil1A domain of the keratin 25 gene is associated with the dominant curly hair coat trait (Crd) in horse

Curly horses present a variety of curl phenotypes that are associated with various degrees of curliness of coat, mane, tail and ear hairs. Their origin is still a matter of debate and several genetic hypotheses have been formulated to explain the diversity in phenotype, including the combination of autosomal dominant and recessive alleles. Our purpose was to map the autosomal dominant curly hair locus and identify the causal variant using genome-wide association study (GWAS) and whole-genome sequencing approaches. A GWAS was performed using a Bayesian sparse linear mixed model, based on 51 curly and 19 straighthaired French and North American horses from 13 paternal families genotyped on the Illumina EquineSNP50 Bead-Chip. A single strong signal was observed on equine chromosome 11, in a region that encompasses the type I keratin gene cluster. This region was refined by haplotype analysis to a segment including 36 genes, among which are 10 keratin genes (KRT-10, -12, -20, -23, -24, -25, -26, -27, -28, -222). To comprehensively identify candidate causal variants within all these genes, whole-genome sequences were obtained for one heterozygous curly stallion and its straighthaired son. Among the four non-synonymous candidate variants identified and validated in the curly region, only variant g. 21891160G> A in the KRT25 gene (KRT25:p.R89H) was in perfect agreement with haplotype status in the whole pedigree. Genetic association was then confirmed by genotyping a larger population consisting of 353 horses. However, five discordant curly horses were observed, which carried neither the variant nor the main haplotype associated with curliness. Sequencing of KRT25 for two discordant horses did not identify any other deleterious variant, which suggests locus rather than allelic heterogeneity for the curly phenotype. We identified the KRT25: p. R89H variant as responsible for the dominant curly trait, but a second dominant locus may also be involved in the shape of hairs within North American Curly horses

New Data from Shovakh Cave and Its Implications for Reconstructing Middle Paleolithic Settlement Patterns in the Amud Drainage, Israel

Abstract: This study presents the geoarchaeological and geochronological aspects of Shovakh Cave and the first comparative context to the nearby Amud Cave (~ 500 m downstream), providing an exceptional opportunity to explore the range of human behaviours within a small geographic area. Sediment samples from two newly excavated areas at the rear and entrance of the cave were analysed using infrared spectroscopy, micromorphology and phytolith analysis and dated through uranium-thorium and luminescence techniques. The rear of the cave shows carnivore activity and low artefact concentrations. It also exhibits a shift in sedimentation from wind-blown deposits to colluviation of terra rossa. Direct dating of the deposits associated with the Middle Palaeolithic (MP) occupation at this area could not be obtained due to the breccia forming at the lower part of the excavation area. However, the later phases of the Middle Palaeolithic occupation at this area gave an age estimate of 45.5 ± 3.7 ka. At the entrance of the cave, there are relatively more residues associated with human use of fire. Post-depositional processes in this area include decalcification of the upper layer, cementation of the lower layer and phosphatisation due to guano decomposition, which indicates that this area was probably roofed. The ages obtained in this area range between 67.5 ± 5.5 to 56.2 ± 5.9 ka, overlapping with the occupation time of Amud cave. The evidence from Shovakh Cave presents lower intensity of occupation compared to Amud, indicating variable modes of site use by humans in the Amud drainage during the Late Middle Palaeolithic

Chondrocytes Play a Major Role in the Stimulation of Bone Growth by Thyroid Hormone

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Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA.

International audienceCerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-γ are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-α/β in ECM development remains unclear. Here, we address the role of the IFN-α/β pathway in ECM devel-opment in response to hepatic or blood-stage PbA infection, using mice deficient for types I or II IFN receptors. While IFN-γR1⁻/⁻ mice were fully resistant, IFNAR1⁻/⁻ mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN-γR1⁻/⁻ mice correlated with unaltered cerebral microcirculation and absence of ischemia, while WT and IFNAR1⁻/⁻ mice developed distinct microvascular pathologies. ECM resistance appeared to be independent of parasitemia. Instead, key mediators of ECM were attenuated in the absence of IFNAR1, including PbA-induced brain sequestration of CXCR3⁺-activated CD8⁺ T cells. This was associated with reduced expression of Granzyme B, IFN-γ, IL-12Rβ2, and T-cell-attracting chemokines CXCL9 and CXCL10 in IFNAR1⁻/⁻ mice, more so in the absence of IFN-γR1. Therefore, the type I IFN-α/β receptor pathway contributes to brain T-cell responses and microvascular pathology, although it is not as essential as IFN-γ for the development of cerebral malaria upon hepatic or blood-stage PbA infection

MOESM1 of A missense variant in the coil1A domain of the keratin 25 gene is associated with the dominant curly hair coat trait (Crd) in horse

Additional file 1: Table S1. List of animals included in the study. This table provides detailed information about identification, pedigree, phenotypes and genotypes of animals included in the study. The full pedigree is also provided. Table S2a. Details on markers and haplotypes in the mapped region. This table provides markers and their position, including the KRT25 variant along ECA11. Colors are used to depict haplotypes, assuming 18 founder haplotypes (12 “non-curly” haplotypes carried by crossbreed animals as well as the six most frequent other haplotypes, including one “curly” haplotype). Haplotypes are given for each animal, according to pedigree data. Table S2b. Delineation of the critical mapping region by haplotype analysis. Haplotypes were sorted out according to their sequence and the associated coat phenotype. Critical recombination events are easily detected by color changes and help identify the upper and lower bounds of the mapping interval. Table S3. PCR primers used to genotype candidate genes. This table provides detailed information about chromosome positions, alleles, gene names, ID, primer sequences, fragment lengths and Tm. Table S4. Statistics on genome-wide detection of functional variants. Table S4 provides statistics on variant detection based on NGS sequencing, with numbers of new and known variants (whole genome and genes) according to their consequence as predicted by VEP. Positional candidate variants are also reported. Table S5. List of gene variants predicted to impact protein functionality. Table S5 includes chromosome positions, alleles, gene ID and functional annotations. The last column (Existing variation) indicates variants; which were already known in dbSNP. Table S6. Concordant variants identified in the critical mapping interval. Table S6 includes chromosome positions, alleles, functional annotations and gene ID for concordant variants. Table S7. Horses genotyped by PCR and Sanger sequencing. Horse names, phenotype and genotype for the KRT24:g.21932167G>T, Top2A:g.22186465C>T and Top2A: g.22191762G>T variants are presented. Table S8. Pedigree information for the progeny of Walker’s Prince T and Dravkvallons Ite O Maguzu. Table S8 provides pedigree and phenotype data obtained from breeders and the Curly horse pedigree database ( http://www.curlyhorses.info/mainsearch.asp ). Table S9. Comparison of NCBI and Ensembl annotations within the keratin cluster on ECA11. Annotation features are listed along ECA11, from position 2,136,900 to 2,197,100 pb; some discrepancy is observed upstream of the critical mapping interval

Middle Pleistocene Homo behavior and culture at 140,000 to 120,000 years ago and interactions with Homo sapiens

International audienceFossils of a Middle Pleistocene (MP) Homo within a well-defined archaeological context at the open-air site of Nesher Ramla, Israel, shed light on MP Homo culture and behavior. Radiometric ages, along with cultural and stratigraphic considerations, suggest that the fossils are 140,000 to 120,000 years old, chronologically overlapping with H. sapiens in western Asia. Lithic analysis reveals that MP Homo mastered stone-tool production technologies, previously known only among H. sapiens and Neanderthals. The Levallois knapping methods they used are indistinguishable from that of concurrent H. sapiens in western Asia. The most parsimonious explanation for such a close similarity is the cultural interactions between these two populations. These findings constitute evidence of contacts and interactions between H. sapiens and MP Homo