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See detailHTLV-1/BLV antisense-RNA dependent host gene perturbation in pre-leukemic and leukemic clones
Rosewick, Nicolas; Durkin, Keith ULg; Marçais, Ambroise et al

in Retrovirology (2015, August 28), 12(1),

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See detailImproving the methodology for the detection of proviral integration sites in the host genome via high throughput sequencing.
Durkin, Keith ULg; Artesi, Maria ULg; Rosewick, Nicolas et al

in Retrovirology (2015, August 28), 12(1),

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See detailImproving proviral integration site detection with high throughput sequencing
Durkin, Keith ULg; Artesi, Maria ULg; Rosewick, Nicolas et al

Poster (2015, May)

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See detailExploring the Deltaretrovirus Tumor Transcriptome: Lessons from RNA-Seq
Rosewick, Nicolas; Durkin, Keith ULg; Thys, Wannes et al

Conference (2014, June)

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See detailIdentification of two noncoding antisense transcripts in BLV and their interaction with the BLV encoded miRNAs
Durkin, Keith ULg; Rosewick, Nicolas; Momont, Mélanie et al

Conference (2014, June)

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See detailIdentification of two antisense transcripts in BLV and their interaction with BLV-encoded microRNAs.
Durkin, Keith ULg; Rosewick, Nicolas; Momont, Mélanie et al

Poster (2014, February)

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See detailElucidating the role of Bovine Leukemia Virus encoded micro-RNAs
Durkin, Keith ULg; Rosewick, Nicolas; Momont, Momont et al

in Retrovirology (2014, January 07), 11(1), 62

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See detailDeep sequencing reveals abundant non-canonical retroviral microRNAs in B-cell leukemia/lymphoma
Durkin, Keith ULg

Scientific conference (2013, January 28)

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See detailDeep sequencing reveals abundant non-canonical retroviral microRNAs in B-cell leukemia/lymphoma
Rosewick, Nicolas; Momont, Mélanie ULg; Durkin, Keith ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2013)

Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy however remains poorly understood, especially as viral ... [more ▼]

Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy however remains poorly understood, especially as viral mRNA/protein are tightly silenced in tumors. Here, using deep sequencing of broad windows of small RNA sizes in the Bovine Leukemia Virus ovine model of leukemia/lymphoma, we provide in vivo evidence of the production of non-canonical Pol IIItranscribed viral microRNAs in leukemic B-cells in the complete absence of Pol II 5’ LTR-driven transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional units located in a proviral region dispensable for in vivo infectivity, BLV microRNAs represent ~ 40 % of all microRNAs in both experimental and natural malignancy. They are subject to strong purifying selection and associate with Argonautes, consistent with a critical function in silencing of important cellular and/or viral targets. BLV microRNAs are strongly expressed in preleukemic and malignant cells in which structural and regulatory gene expression is repressed, suggesting a key role in tumor onset and progression. Understanding how Pol III-dependent microRNAs subvert cellular and viral pathways will contribute in deciphering the intricate perturbations that underlie malignant transformation. [less ▲]

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See detailDetection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy
Dupuis, Marie-Capucine; Zhang, Zhiyan ULg; Durkin, Keith ULg et al

in Animal Genetics (2013)

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with ... [more ▼]

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with recurrent laryngeal neuropathy (RLN), an important equine upper airway disease compromising performance. A total of 2797 CNVs were detected for 477 horses, covering 229 kb and seven SNPs on average. Overlapping CNVs were merged to define 478 CNV regions (CNVRs). CNVRs, particularly deletions, were shown to be significantly depleted in genes. Fifty-two of the 67 common CNVRs (frequency ! 1%) were validated by association mapping, Mendelian inheritance, and/or Mendelian inconsistencies. None of the 67 common CNVRs were significantly associated with RLN when accounting for multiple testing. However, a duplication on chromosome 10 was detected in 10 cases (representing three breeds) and two unphenotyped parents but in none of the controls. The duplication was embedded in an 8-Mb haplotype shared across breeds. [less ▲]

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See detailSerial translocation via circular intermediates underlies color-sidedness in cattle.
Durkin, Keith ULg

Scientific conference (2012, May 04)

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See detailSerial translocation by means of circular intermediates underlies colour sidedness in cattle.
Durkin, Keith ULg; Coppieters, Wouter ULg; Drogemuller, Cord et al

in Nature (2012), 482(7383), 81-4

Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik ... [more ▼]

Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs(29)), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs(6)), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism. [less ▲]

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See detailThe bovine genomic DNA sequence data reveal three IGHV subgroups, only one of which is functionally expressed
Niku, Mikael; Liljavirta, Jenni; Durkin, Keith ULg et al

in Developmental & Comparative Immunology (2012), 37

A comprehensive analysis of cattle shotgun sequencing data reveals 36 immunoglobulin heavy chain variable genes. The previously described bovine subgroup IGHV1 contains 10 functional genes with a ... [more ▼]

A comprehensive analysis of cattle shotgun sequencing data reveals 36 immunoglobulin heavy chain variable genes. The previously described bovine subgroup IGHV1 contains 10 functional genes with a conserved promoter including the consensus octamer and several other transcription factor binding sites, intact exons and matching cDNA sequences. Subgroups IGHV2 and IGHV3 consist entirely of pseudogenes. Thus, the bovine germline IGHV repertoire is very limited. The IGHV genes are distributed in mammalian clans I and II, while no clan III genes were detected. Clan-specific PCR of genomic DNA from cattle, sheep, Eurasian elk, white-tailed deer, pig and dolphin indicates highly dynamic evolution of IGHV gene usage within Cetartiodactyla. The bovine germline IGHV repertoire was probably generated by recent duplications of an IGHV1-IGHV2 homology unit. Immunoglobulin heavy chain genes are largely incorrectly assembled in the current cattle genome versions Btau_4.2 and UMD_3.1. FISH experiments confirm an IGHV locus close to terminus of BTA21. [less ▲]

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See detailMolecular dissection of the color-sided phenotype in cattle reveals a novel mechanism of chromosome evolution involving circular shuttling intermediates.
Durkin, Keith ULg; Cambisano, Nadine ULg; Ahariz, Naïma ULg et al

in Chromosome Research : An International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology (2011, May), 19(S1), 18

The color-sided (Cs) phenotype is a dominant coat color pattern segregating in several breeds including Belgian Blue Cattle (BBC) and Brown Swiss (BS). A genome-wide association study performed in BBC ... [more ▼]

The color-sided (Cs) phenotype is a dominant coat color pattern segregating in several breeds including Belgian Blue Cattle (BBC) and Brown Swiss (BS). A genome-wide association study performed in BBC unambiguously positioned the Cs locus on chromo- some 29 (BTA29); however, SNP arrays and CGH detected an equally perfectly associated <480 kb duplication encompassing the KIT gene on chromo- some 6 (BTA6). FISH analysis reconciled these results by revealing an intrachromosomal duplication, which transposed a fragment of BTA6 to BTA29. The organization of the duplicated segment, including breakpoint definition, was determined by high-throughput resequencing and revealed that the transpo- sition occurred via a circular intermediate. The trans- posed KIT copy was shown to be transcriptionally competent, suggesting that dominant color-sidedness results from dysregulated expression of KIT. Similar analyses of the color-sided phenotype conducted in BS revealed linkage on BTA6, a <120- kb-BTA6 duplication (which overlaps with the BBC duplication), and a <414-kb-BTA29 duplication adja- cent to the BTA29 breakpoint defined in BBC. FISH analysis showed the duplicated portion of BTA29 was located on BTA6 and adjacent to the KIT gene. SNP genotyping indicated that the BTA6 and BTA29 haplotypes associated with color-sidedness in BS and BBC were near identical, demonstrating the non-independence of the two chromosomal events. High-throughput resequencing of a color-sided BS animal defined the corresponding breakpoints and suggests that the BS Cs allele is derived from the BBC duplication [less ▲]

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See detailCytogenetic Evaluation of the Stallion
Durkin, Keith ULg; Raudsepp, Terje; Chowdhary, Bhanu P

in McKinnon, Angus O; Squires, Edward L; Vaala, Wendy E (Eds.) et al Equine Reproduction (2011)

A normal chromosome complement is essential for normal fertility. Chromosome aberrations – numerical or structural – may lead to a range of deformities and defects that can be physical and/or ... [more ▼]

A normal chromosome complement is essential for normal fertility. Chromosome aberrations – numerical or structural – may lead to a range of deformities and defects that can be physical and/or physiological. Irrespectively, aberrations result in complete loss of fertility or reduced fertility in stallions. They lead to the production of abnormal gametes that contribute to early embryonic deaths. Moreover, viable offspring from such gametes may carry the same chromosomal abnormality and have similar fertility problems. Economic losses incurred due to reduced stallion fertility or infertility is huge. Cytogenetic analysis is a simple and straightforward approach to ensure that the animals have a normal chromosome complement. To protect the economic interests of horse owners, breeders, prospective buyers, insurance companies, etc., the equine industry is strongly encouraged to mandate cytogenetic analysis of all breeding animals at an early age. The relatively inexpensive practice will also prevent the spread of chromosome aberrations as is expected from the progenies of the A P Valentine – a fairly successfully horse on the race track – and similar other carriers of abnormalities. [less ▲]

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See detailMolecular heterogeneity of XY sex reversal in horses
Raudsepp, T; Durkin, Keith ULg; Lear, T.L. et al

in Animal Genetics (2010), 41

Male-to-female 64,XY sex reversal is a frequently reported chromosome abnormality in horses. Despite this, the molecular causes of the condition are as yet poorly understood. This is partially because ... [more ▼]

Male-to-female 64,XY sex reversal is a frequently reported chromosome abnormality in horses. Despite this, the molecular causes of the condition are as yet poorly understood. This is partially because only limited molecular information is available for the horse Y chro- mosome (ECAY). Here, we used the recently developed ECAY map and carried out the first comprehensive study of the Y chromosome in XY mares (n = 18). The integrity of the ECAY in XY females was studied by FISH and PCR using markers evenly distributed along the euchromatic region. The results showed that the XY sex reversal condition in horses has two molecularly distinct forms: (i) a Y-linked form that is characterized by Y chromosome deletions and (ii) a non-Y-linked form where the Y chromosome of affected females is molecularly the same as in normal males. Further analysis of the Y-linked form (13 cases) showed that the condition is molecularly heterogeneous: the smallest deletions spanned about 21 kb, while the largest involved the entire euchromatic region. Regardless of the size, all deletions included the SRY gene. We show that the deletions were likely caused by inter-chromatid recombination events between repeated sequences in ECAY. Further, we hypothesize that the occurrence of SRY-negative XY females in some species (horse, human) but not in others (pig, dog) is because of differences in the organization of the Y chromosome. Finally, in contrast to the Y-linked SRY-negative form of equine XY sex reversal, the molecular causes of SRY-positive XY mares (5 cases) remain as yet undefined. [less ▲]

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See detailMapping Athletic Performance Related Genes in the Equine Genome and a Genome Scan for Superior Athletic Performance in the Thoroughbred
Durkin, Keith ULg

Doctoral thesis (2009)

The primary goal of the Thoroughbred industry is to breed and train superior equine athletes capable of excelling on the racetrack. To date, research into the genetic underpinnings of athletic ability has ... [more ▼]

The primary goal of the Thoroughbred industry is to breed and train superior equine athletes capable of excelling on the racetrack. To date, research into the genetic underpinnings of athletic ability has been limited in the horse. Advances in equine genomics and the genetics of athletic performance in humans have opened up the possibility of investigating this important trait in the Thoroughbred. Initially, 46 candidate genes associated with human athletic performance were mapped in the equine genome by radiation hybrid (RH) and fluorescent in situ hybridization (FISH) mapping. RH data and later the draft equine genomic sequence allowed us to identify microsatellites adjacent to these and other candidate genes (95 in total). Additional microsatellites were added to increase genome coverage, producing a final panel of 186 markers. All the potential markers were initially screened on a pool of DNA for 16 Thoroughbreds to ensure they were polymorphic. The panel was genotyped on 162 Thoroughbreds in total; Centimorgans (cM) between microsatellites were determined with CRI-MAP. The animal’s athletic ability was estimated using career winnings loge transformed to create a linear trait; unraced animals were treated as missing data. Linkage analysis was carried out using the MERLIN program, and association analysis was carried out using the QTDT program. Appropriate thresholds for statistical significance were determined by carrying out 1000 simulated genome scans based on the structure of the original data. LOD scores above 1.54 met the criteria of statistical significance (with a 5% chance of type I error). In the actual genome scan, the marker L12.2 had the highest observed LOD score of 1.16 and p-value of 0.01 and consequently was not significant; the association analysis also did not detect significant association with performance on the track. Given the complexity of the phenotype under investigation and the modest sample size, the lack of linkage/association was not unexpected. Nevertheless, this study has contributed to the RH and FISH maps of the equine genome. Additionally, the development of the genome scanning panel for this study has provided useful information on the most informative microsatellites for linkage or association studies in the Thoroughbred. [less ▲]

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See detailA genome scan for athletic performance in the thoroughbred.
Durkin, Keith ULg; Raudsepp, T; Skow, L.C. et al

Poster (2008, July)

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See detailPrecise demarcation of the breakpoint in a thoroughbred stallion carrying a ECA5 and ECA16 Translocation.
Durkin, Keith ULg; Raudsepp, T; Chowdhary, B.P.

in Proceedings of Plant & Animal Genome XVI (2008, January)

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