Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes

Massese is an Italian dairy sheep breed characterized by animals with black skin and horns and black or apparent grey hairs. Owing to the presence of these two coat colour types, this breed can be considered an interesting model to evaluate the effects of coat colour gene polymorphisms on this phenotypic trait. Two main loci have been already shown to affect coat colour in sheep: Agouti and Extension coding for the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes, respectively. The Agouti locus is affected by a large duplication including the ASIP gene that may determine the Agouti white and tan allele (AWt). Other disrupting or partially inactivating mutations have been identified in exon 2 (a deletion of 5 bp, D5; and a deletion of 9 bp, D9) and in exon 4 (g.5172T.A, p.C126S) of the ASIP gene. Three missense mutations in the sheep MC1R gene cause the dominant black ED allele (p.M73K and p.D121N) and the putative recessive e allele (p.R67C). Here, we analysed these ASIP and MC1R mutations in 161 Massese sheep collected from four flocks. The presence of one duplicated copy allele including the ASIP gene was associated with grey coat colour (P59.4E-30). Almost all animals with a duplicated copy allele (37 out of 41) showed uniform apparent grey hair and almost all animals without a duplicated allele (117 out of 120) were completely black. Different forms of duplicated alleles were identified in Massese sheep including, in almost all cases, copies with exon 2 disrupting or partially inactivating mutations making these alleles different from the AWt allele. A few exceptions were observed in the association between ASIP polymorphisms and coat colour: three grey sheep did not carry any duplicated copy allele and four black animals carried a duplicated copy allele. Of the latter four sheep, two carried the ED allele of the MC1R gene that may be the cause of their black coat colour. The coat colour of all other black animals may be determined by non-functional ASIP alleles (non-agouti alleles, Aa) and in a few cases by the ED Extension allele. At least three frequent ASIP haplotypes ([D5:g.5172T], [N:g.5172A] and [D5:g.5172A]) were detected (organized into six different diplotypes). In conclusion, the results indicated that coat colours in the Massese sheep breed are mainly derived by combining ASIP and MC1R mutations

A first comparative map of copy number variations in the sheep genome

We carried out a cross species cattle–sheep array comparative genome hybridization experiment to identify copy number variations (CNVs) in the sheep genome analysing ewes of Italian dairy or dual-purpose breeds (Bagnolese, Comisana, Laticauda, Massese, Sarda, and Valle del Belice) using a tiling oligonucleotide array with ~385,000 probes designed on the bovine genome. We identified 135 CNV regions (CNVRs; 24 reported in more than one animal) covering ~10.5 Mb of the virtual sheep genome referred to the bovine genome (0.398%) with a mean and a median equal to 77.6 and 55.9 kb, respectively. A comparative analysis between the identified sheep CNVRs and those reported in cattle and goat genomes indicated that overlaps between sheep and both other species CNVRs are highly significant (Pb0.0001), suggesting that several chromosome regions might contain recurrent interspecies CNVRs. Many sheep CNVRs include genes with important biological functions. Further studies are needed to evaluate their functional relevance

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Abstract BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD

Genetic parameters for somatic cell score according to udder infection status in Valle del Belice dairy sheep and impact of imperfect diagnosis of infection

<p>Abstract</p> <p>Background</p> <p>Somatic cell score (SCS) has been promoted as a selection criterion to improve mastitis resistance. However, SCS from healthy and infected animals may be considered as separate traits. Moreover, imperfect sensitivity and specificity could influence animals' classification and impact on estimated variance components. This study was aimed at: (1) estimating the heritability of bacteria negative SCS, bacteria positive SCS, and infection status, (2) estimating phenotypic and genetic correlations between bacteria negative and bacteria positive SCS, and the genetic correlation between bacteria negative SCS and infection status, and (3) evaluating the impact of imperfect diagnosis of infection on variance component estimates.</p> <p>Methods</p> <p>Data on SCS and udder infection status for 1,120 ewes were collected from four Valle del Belice flocks. The pedigree file included 1,603 animals. The SCS dataset was split according to whether animals were infected or not at the time of sampling. A repeatability test-day animal model was used to estimate genetic parameters for SCS traits and the heritability of infection status. The genetic correlation between bacteria negative SCS and infection status was estimated using an MCMC threshold model, implemented by Gibbs Sampling.</p> <p>Results</p> <p>The heritability was 0.10 for bacteria negative SCS, 0.03 for bacteria positive SCS, and 0.09 for infection status, on the liability scale. The genetic correlation between bacteria negative and bacteria positive SCS was 0.62, suggesting that they may be genetically different traits. The genetic correlation between bacteria negative SCS and infection status was 0.51. We demonstrate that imperfect diagnosis of infection leads to underestimation of differences between bacteria negative and bacteria positive SCS, and we derive formulae to predict impacts on estimated genetic parameters.</p> <p>Conclusions</p> <p>The results suggest that bacteria negative and bacteria positive SCS are genetically different traits. A positive genetic correlation between bacteria negative SCS and liability to infection was found, suggesting that the approach of selecting animals for decreased SCS should help to reduce mastitis prevalence. However, the results show that imperfect diagnosis of infection has an impact on estimated genetic parameters, which may reduce the efficiency of selection strategies aiming at distinguishing between bacteria negative and bacteria positive SCS.</p

The X-ray properties of million solar mass black holes

We present new Chandra X-ray observations of seven low-mass black holes (~1e6 Msun) accreting at low Eddington ratios between -2.0<log L/Ledd<-1.5. We compare the X-ray properties of these seven low-mass active galactic nuclei (AGN) to a total of 73 other low-mass AGN in the literature with published Chandra observations (with Eddington ratios extending from -2.0<log L/Ledd<-0.1). We do not find any statistical differences between low- and high-Eddington ratio low-mass AGN in the distributions of their X-ray to ultraviolet luminosity ratios (aox), or in their X-ray spectral shapes. Furthermore, the aox distribution of low-L/Ledd AGN displays an X-ray weak tail that is also observed within high-L/Ledd objects. Our results indicate that between -2<log L/Ledd<-0.1, there is no systematic change in the structure of the accretion flow for active galaxies hosting 1e6 Msun black holes. We examine the accuracy of current bolometric luminosity estimates for our low-L/Ledd objects with new Chandra observations, and it is plausible that their Eddington ratios could be underestimated by up to an order of magnitude. If so, then in analogy with weak emission line quasars, we suggest that accretion from a geometrically thick, radiatively inefficient `slim disk' could explain their diverse properties in aox. Alternatively, if current Eddington ratios are in fact correct (or overestimated), then the X-ray weak tail would imply that there is diversity in disk/corona couplings among individual low-mass objects. Finally, we conclude by noting that the aox distribution for low-mass black holes may have favorable consequences for the epoch of cosmic reionization being driven by AGN.Comment: 14 pages, 6 figures, 6 tables. Accepted for publication in Ap

Missense and nonsense mutations in melanocortin 1 receptor (MC1R) gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences

<p>Abstract</p> <p>Background</p> <p><it>Agouti </it>and <it>Extension </it>loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The <it>Extension </it>locus encodes the melanocortin 1 receptor (MC1R) whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals.</p> <p>Results</p> <p>The whole coding region of the <it>MC1R </it>gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F₁goats and the parental animals). Five single nucleotide polymorphisms (SNPs) were identified: one nonsense mutation (p.Q225X), three missense mutations (p.A81V, p.F250V, and p.C267W), and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour.</p> <p>Conclusion</p> <p>According to the results obtained in the investigated goat breeds, <it>MC1R </it>mutations may determine eumelanic and pheomelanic phenotypes. However, they are probably not the only factors. In particular, the surprising not complete association of the nonsense mutation (p.Q225X) with red coat colour raises a few hypotheses on the determination of pheomelanic phenotypes in goats that should be further investigated.</p

Does the intermediate-mass black hole in LEDA 87300 (RGG 118) follow the near-quadratic Mbh-Mspheroid relation?

The mass scaling relation between supermassive black holes and their host spheroids has previously been described by a quadratic or steeper relation at low masses (105 &lt; Mbh/Mo ≲ 107). How this extends into the realm of intermediate-mass black holes (102 &lt; Mbh/Mo &lt; 105) is not yet clear, although for the barred Sm galaxy LEDA 87300, Baldassare et al. recently reported a nominal virial mass of Mbh = 5 104 Mo residing in a "spheroid" of stellar mass equal to 6.3 108 Mo. We point out, for the first time, that LEDA 87300 therefore appears to reside on the near-quadratic Mbh-Msph,∗ relation. However, Baldassare et al. modeled the bulge and bar as the single spheroidal component of this galaxy. Here we perform a 3-component bulge+bar+disk decomposition and find a bulge luminosity which is 7.7 times fainter than the published "bulge" luminosity. After correcting for dust, we find that Mbulge = 0.9 108 Mo and Mbulge/Mdisk = 0.04 - which is now in accord with ratios typically found in Scd-Sm galaxies. We go on to discuss slight revisions to the stellar velocity dispersion (40 11 km s-1) and black hole mass () and show that LEDA 87300 remains consistent with the Mbh-σ relation, and also the near-quadratic Mbh-Msph,∗ relation when using the reduced bulge mass. LEDA 87300 therefore offers the first support for the rapid but regulated (near-quadratic) growth of black holes, relative to their host bulge/spheroid, extending into the domain of intermediate-mass black holes

Whole mitochondrial genomes unveil the impact of domestication on goat matrilineal variability

Background: The current extensive use of the domestic goat (Capra hircus) is the result of its medium size and high adaptability as multiple breeds. The extent to which its genetic variability was influenced by early domestication practices is largely unknown. A common standard by which to analyze maternally-inherited variability of livestock species is through complete sequencing of the entire mitogenome (mitochondrial DNA, mtDNA). Results: We present the first extensive survey of goat mitogenomic variability based on 84 complete sequences selected from an initial collection of 758 samples that represent 60 different breeds of C. hircus, as well as its wild sister species, bezoar (Capra aegagrus) from Iran. Our phylogenetic analyses dated the most recent common ancestor of C. hircus to ~460,000 years (ka) ago and identified five distinctive domestic haplogroups (A, B1, C1a, D1 and G). More than 90 % of goats examined were in haplogroup A. These domestic lineages are predominantly nested within C. aegagrus branches, diverged concomitantly at the interface between the Epipaleolithic and early Neolithic periods, and underwent a dramatic expansion starting from ~12–10 ka ago. Conclusions: Domestic goat mitogenomes descended from a small number of founding haplotypes that underwent domestication after surviving the last glacial maximum in the Near Eastern refuges. All modern haplotypes A probably descended from a single (or at most a few closely related) female C. aegagrus. Zooarchaelogical data indicate that domestication first occurred in Southeastern Anatolia. Goats accompanying the first Neolithic migration waves into the Mediterranean were already characterized by two ancestral A and C variants. The ancient separation of the C branch (~130 ka ago) suggests a genetically distinct population that could have been involved in a second event of domestication. The novel diagnostic mutational motifs defined here, which distinguish wild and domestic haplogroups, could be used to understand phylogenetic relationships among modern breeds and ancient remains and to evaluate whether selection differentially affected mitochondrial genome variants during the development of economically important breeds

The Young Supernova Experiment: Survey Goals, Overview, and Operations

Time domain science has undergone a revolution over the past decade, with tens of thousands of new supernovae (SNe) discovered each year. However, several observational domains, including SNe within days or hours of explosion and faint, red transients, are just beginning to be explored. Here, we present the Young Supernova Experiment (YSE), a novel optical time-domain survey on the Pan-STARRS telescopes. Our survey is designed to obtain well-sampled $griz$ light curves for thousands of transient events up to $z \approx 0.2$. This large sample of transients with 4-band light curves will lay the foundation for the Vera C. Rubin Observatory and the Nancy Grace Roman Space Telescope, providing a critical training set in similar filters and a well-calibrated low-redshift anchor of cosmologically useful SNe Ia to benefit dark energy science. As the name suggests, YSE complements and extends other ongoing time-domain surveys by discovering fast-rising SNe within a few hours to days of explosion. YSE is the only current four-band time-domain survey and is able to discover transients as faint $\sim$21.5 mag in $gri$ and $\sim$20.5 mag in $z$, depths that allow us to probe the earliest epochs of stellar explosions. YSE is currently observing approximately 750 square degrees of sky every three days and we plan to increase the area to 1500 square degrees in the near future. When operating at full capacity, survey simulations show that YSE will find $\sim$5000 new SNe per year and at least two SNe within three days of explosion per month. To date, YSE has discovered or observed 8.3% of the transient candidates reported to the International Astronomical Union in 2020. We present an overview of YSE, including science goals, survey characteristics and a summary of our transient discoveries to date.Comment: ApJ, in press; more information at https://yse.ucsc.edu