Delta-Globin Gene Expression Is Enhanced in vivo by Interferon Type I

Beta hemoglobinopathies are widely spread monogenic lethal diseases. Delta-globin gene activation has been proposed as a possible approach for curing these pathologies. The therapeutic potential of delta-globin, the non-alpha component of Hemoglobin A2 (α2δ2; HbA2), has been demonstrated in a mouse model of beta thalassemia, while its anti-sickling effect, comparable to that of gamma globin, was established some time ago. Here we show that the delta-globin mRNA level is considerably increased in a Deoxyribonuclease II-alpha knockout mouse model in which type 1 interferon (interferon beta, IFNb) is activated. IFNb activation in the fetal liver improves the delta-globin mRNA level, while the beta-globin mRNA level is significantly reduced. In addition, we show that HbA2 is significantly increased in patients with multiple sclerosis under type 1 interferon treatment. Our results represent a proof of principle that delta-globin expression can be enhanced through the use of molecules. This observation is potentially interesting in view of a pharmacological approach able to increase the HbA2 level

Short communication: An association analysis between one missense polymorphism at the SREBF1 gene and milk yield and composition traits in goats

Sterol regulatory element binding transcription factor 1 (SREBF1) regulates the expression of genes involved in the biosynthesis of fatty acids and cholesterol. Herewith, we have sequenced the near-complete coding region and part of the 3?UTR of the goat SREBF1 gene. In doing so, we have detected a missense c.353CT polymorphism causing a proline to leucine substitution at position 118 (P118L). An association analysis with milk composition traits recorded in MurcianoGranadina goats only revealed a statistical tendency linking SREBF1 genotype and milk omega-3 fatty acid content. The lack of significant associations suggests that the P118L substitution does not involve a functional change.Le facteur de transcription de´nomme´ Sterol regulatory element binding transcription factor 1 (SREBF1) re´gule l’expression des ge`nes implique´s dans la biosynthe`se des acides gras et du choleste´rol. Dans cette e´tude, nous avons se´quence´ la quasi-totalite´ de la re´gion codante et une partie du la re´gion 3?UTR du ge`ne SREBF1 de la che`vre. Ce travail, nous a permis d’identifier un polymorphisme non-synonyme c.353CT causant la substitution d’une Proline en Leucine a` la position 118. L’e´tude d’association avec la composition du lait enregistre´e en che`vres Murciano-Granadina, a re´ve´le´ seulement une tendance statistique reliant SREBF1 ge´notype et l’acide gras ome´ga-3 du lait. L’absence d’associations significatives sugge`re que la substitution P118L n’implique pas un changement fonctionnel

Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150–154 Mb), Oar6 (4–49 Mb) and Oar13 (68–74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection.Publishe

Romanian wild boars and Mangalitza pigs have a European ancestry and harbour genetic signatures compatible with past population bottlenecks

We aimed to analyse the genetic diversity of Romanian wild boars and to compare it with that from other wild boar and pig populations from Europe and Asia. Partial sequencing of the mitochondrial encoded cytochrome b (MT-CYB) gene from 36 Romanian wild boars and 36 domestic pigs (Mangalitza, Bazna and Vietnamese breeds) showed that the diversity of Romanian wild boars and Mangalitza pigs is fairly reduced and that most of the members of these two populations share a common MT-CYB haplotype. Besides, in strong contrast with the Bazna animals, Romanian wild boars and Mangalitza swine did not carry Asian variants at the MT-CYB locus. The autosomal genotyping of 18 Romanian wild boars with the Illumina Porcine SNP60 BeadChip revealed that their genetic background is fundamentally European, even though signs of a potential Near Eastern ancestry (~25%) were detectable at K = 4 (the most significant number of clusters), but not at higher K-values. Admixture analysis also showed that two wild boars are of a hybrid origin, which could be explained by the mating of feral animals with domestic pigs. Finally, a number of Romanian wild boars displayed long runs of homozygosity, an observation that is consistent with the occurrence of past population bottlenecks and the raise of inbreeding possibly due to overhunting or to the outbreak of infectious diseases.This article was published under the frame of the European Social Fund, Human Resources Development Operational Program 2007–2013, project no. POSDRU/159/1.5/S/132765 awarded to VB. Part of the research presented in this publication was funded by grant AGL2013-48742-C2-1-R awarded by the Spanish Ministry of Economy and Competitivity to MA. We also acknowledge the support of the Spanish Ministry of Economy and Competitivity for the Center of Excellence Severo Ochoa 2016-2019 (SEV-2015-0533) grant awarded to the Center for Research in Agricultural Genomics.Peer reviewe

Analyse d’association entre un polymorphisme non synonyme dans le gène SREBF1 et la production et la composition laitières chez les chèvres.

[EN]: Sterol regulatory element binding transcription factor 1 (SREBF1) regulates the expression of genes involved in the biosynthesis of fatty acids and cholesterol. Herewith, we have sequenced the near-complete coding region and part of the 3′UTR of the goat SREBF1 gene. In doing so, we have detected a missense c.353C>T polymorphism causing a proline to leucine substitution at position 118 (P118L). An association analysis with milk composition traits recorded in Murciano-Granadina goats only revealed a statistical tendency linking SREBF1 genotype and milk omega-3 fatty acid content. The lack of significant associations suggests that the P118L substitution does not involve a functional change.[FR]: Le facteur de transcription dénommé Sterol regulatory element binding transcription factor 1 (SREBF1) régule l'expression des gènes impliqués dans la biosynthèse des acides gras et du cholestérol. Dans cette étude, nous avons séquencé la quasi-totalité de la région codante et une partie du la région 3′UTR du gène SREBF1 de la chèvre. Ce travail, nous a permis d'identifier un polymorphisme non-synonyme c.353C> T causant la substitution d'une Proline en Leucine à la position 118. L’étude d'association avec la composition du lait enregistrée en chèvres Murciano-Granadina, a révélé seulement une tendance statistique reliant SREBF1 génotype et l'acide gras oméga-3 du lait. L'absence d'associations significatives suggère que la substitution P118L n'implique pas un changement fonctionnel.This research was funded by projects AGL2007-66161-C02-01 and AGL2007-66161-C02-02. A. Zidi received fellowships of the Spanish Agency of International Cooperation and Development and of the Centre for Research in Agrigenomics (CRAG). Arianna Manunza received a postdoctoral fellowship from the Centre for Research in Agrigenomics (CRAG).Peer reviewe

A high throughput genotyping approach reveals distinctive autosomal genetic signatures for European and Near Eastern wild boar

The lack of a Near Eastern genetic signature in modern European porcine breeds indicates that, although domestic pigs from the Fertile Crescent entered Europe during the Neolithic, they were completely replaced by their European counterparts in a short window of time. Whilst the absence of such genetic signature has been convincingly demonstrated at the mitochondrial level, variation at the autosomal genomes of European and Near Eastern Sus scrofa has not been compared yet. Herewith, we have explored the genetic relationships among 43 wild boar from Europe (N = 21), Near East (N = 19) and Korea (N = 3), and 40 Iberian (N = 16), Canarian (N = 4) and Mangalitza (N = 20) pigs by using a high throughput SNP genotyping platform. After data filtering, 37,167 autosomal SNPs were used to perform population genetics analyses. A multidimensional scaling plot based on genome-wide identity-by-state pairwise distances inferred with PLINK showed that Near Eastern and European wild boar populations are genetically differentiated. Maximum likelihood trees built with TreeMix supported this conclusion i.e. an early population split between Near Eastern and European Sus scrofa was observed. Moreover, analysis of the data with Structure evidenced that the sampled Iberian, Canarian and Mangalitza pigs did not carry any autosomal signature compatible with a Near Eastern ancestry, a finding that agrees well with previous mitochondrial studies

Ethiopian indigenous goats offer insights into past and recent demographic dynamics and localadaptation in sub-Saharan African goats

Abstract Knowledge on how adaptive evolution and human socio‐cultural and economic interests shaped livestock genomes particularly in sub‐Saharan Africa remains limited. Ethiopia is in a geographic region that has been critical in the history of African agriculture with ancient and diverse human ethnicity and bio‐climatic conditions. Using 52K genome‐wide data analysed in 646 individuals from 13 Ethiopian indigenous goat populations, we observed high levels of genetic variation. Although runs of homozygosity (ROH) were ubiquitous genome‐wide, there were clear differences in patterns of ROH length and abundance and in effective population sizes illustrating differences in genome homozygosity, evolutionary history, and management. Phylogenetic analysis incorporating patterns of genetic differentiation and gene flow with ancestry modelling highlighted past and recent intermixing and possible two deep ancient genetic ancestries that could have been brought by humans with the first introduction of goats in Africa. We observed four strong selection signatures that were specific to Arsi‐Bale and Nubian goats. These signatures overlapped genomic regions with genes associated with morphological, adaptation, reproduction and production traits due possibly to selection under environmental constraints and/or human preferences. The regions also overlapped uncharacterized genes, calling for a comprehensive annotation of the goat genome. Our results provide insights into mechanisms leading to genome variation and differentiation in sub‐Saharan Africa indigenous goats