1,721,031 research outputs found
A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle
Get PDFGenodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913)
Molecular characterization of ovine GM1 gangliosidosis
Get PDFOvine GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder. Affected lambs are born relatively normal, however at approximately four months of age they begin exhibiting severe neurological symptoms. Pathology progresses rapidly in affected lambs ultimately resulting in death by five to six months of age. In humans and other species, mutations in the β-galactosidase (GLB1) gene are responsible for similar disease phenotypes. The production of non-functional β-galactosidase results in a buildup of GM1 gangliosides and other terminally linked galactose-containing molecules in the brain and visceral tissues. Using the Illumina® OvineSNP50 BeadChip platform, seven affected and ten unaffected animals were genotyped and a genome wide association analysis was performed using PLINK. A significant association was detected for multiple SNPs on OAR19; further investigation showed this area was orthologous to HSA3 containing GLB1. Sequence analysis revealed a G to T nucleotide transversion in exon six of ovine GLB1 resulting in a nonsynonymous cysteine to phenylalanine (Cys229Phe) amino acid substitution. A PCR-RFLP assay using AciI restriction enzyme was designed for genotyping lambs. To date, 1664 animals have been genotyped using the DNA-based diagnostic and all affected lambs were homozygous for this mutation. Conversely, individuals with normal phenotypes were either heterozygous or homozygous for the alternative allele. Affected lambs will be used as an animal model to further explore the disease and potentially identify therapies for humans.Item withdrawn by Mark Zulauf ([email protected]) on 2012-12-07T21:18:40Z
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Sequence characterization of the HSA12/22/12 evolutionary breakpoint region on SSC5q21
Get PDFThe HSA12/22/12 evolutionary breakpoint region on SSC5q21 has been sequenced, further localized, and preliminarily characterized. The existence and location of the breakpoint regions were originally determined in the human-porcine comparative map constructed by Meyers and colleagues. Bacterial artificial chromosome (BAC) fingerprint analysis and radiation hybrid mapping of BAC-end sequences was used to construct a minimum tiling path (MTP) encompassing each breakpoint region. The MTP clones were sequenced. The MTP sequences were then evaluated for similarity to human sequences using the NCBI cross-species megaBLAST program on Build 37.3 of the human genome. The more centromeric HSA12/22 breakpoint region displays sequence similarity to megabase (Mb) positions 2.593-2.807 on HSA12 and 17.583-17.672 on HSA22, and the more telomeric HSA22/12 breakpoint region displays sequence similarity to Mb positions 18.566-18.660 on HSA22 and 34.252-49.523 on HSA12. The human genome coordinates corresponding to the HSA12/22 breakpoint region also suggest an alternative marker order to the marker order proposed by Meyers and colleagues, although additional research is necessary to finalize the true marker order. The sequence evidence indicates the presence of transposable elements and AT-rich sequence composition in the areas surrounding each of the breakpoint regions. The sequence characterization results are in agreement with several previous studies of evolutionary breakpoint regions and therefore suggest potential involvement of such factors in evolutionary breakpoint generation, although underlying molecular mechanisms remain poorly understood at this point in time.Item withdrawn by Mark Zulauf ([email protected]) on 2012-04-27T12:44:41Z
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
QTL Mapping and Molecular Dissection of Meat Quality Traits in Swine
No full text134 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007.Improvement of meat quality is important for consumer satisfaction. As many pork quality traits cannot be assessed in the live animal, selection for these traits must rely upon genetic determinants known as quantitative trait loci (QTL). To facilitate fine-mapping of swine QTL, a ∼1 Mb-resolution human-pig comparative map, composed of 2,274 markers in 34 linkage groups, was constructed using the radiation hybrid method. Comparative analyses revealed 51 conserved synteny groups, including 173 conserved segments, and overall comparative coverage greater than 90%. This map was used, together with porcine linkage and bacterial artificial chromosome (BAC) physical maps, to fine-map a QTL affecting pork tenderness that was detected, on the q arm of porcine chromosome 2 (SSC2q), within the Illinois Meat Quality Pedigree (IMQP). Nine novel microsatellite markers within the ∼30-Mb region surrounding the most likely QTL position, including one within the candidate gene calpastatin (CAST), were developed. These markers, along with nine publicly-available markers, were used to perform linkage and haplotype analyses within the IMQP. Within-family linkage analyses revealed at least two families segregating for a highly-significant QTL in strong positional agreement with CAST. A combined analysis of these two families yielded QTL intervals of 36 cM and 7 cM for Instron shear force and taste panel tenderness, respectively, while haplotype analyses suggested further refinement to a 1.8 cM interval containing CAST. To identify allelic variation that may influence pork tenderness, the complete genomic sequence of porcine CAST was determined. Nearly 77.6% of this gene was then re-sequenced from each of six IMQP F1 boars. Based on heterozygosity, 393 of 896 discovered polymorphisms appeared concordant with previous QTL data. The location of this variation within the CAST gene suggests that a causative mutation is likely to be regulatory. Functional characterization of CAST variation should enhance understanding of the molecular basis of pork tenderness, and thus allow for genetic improvement of pork products. The effectiveness of CAST polymorphisms for marker-assisted selection (MAS) of pork tenderness can now be assessed. Furthermore, genomic resources developed in this study may be used to investigate many other porcine QTL, including additional tenderness QTL suggested on SSC2q.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD
QTL Mapping and Molecular Dissection of Meat Quality Traits in Swine
No full textImprovement of meat quality is important for consumer satisfaction. As many pork quality traits cannot be assessed in the live animal, selection for these traits must rely upon genetic determinants known as quantitative trait loci (QTL). To facilitate fine-mapping of swine QTL, a ∼1 Mb-resolution human-pig comparative map, composed of 2,274 markers in 34 linkage groups, was constructed using the radiation hybrid method. Comparative analyses revealed 51 conserved synteny groups, including 173 conserved segments, and overall comparative coverage greater than 90%. This map was used, together with porcine linkage and bacterial artificial chromosome (BAC) physical maps, to fine-map a QTL affecting pork tenderness that was detected, on the q arm of porcine chromosome 2 (SSC2q), within the Illinois Meat Quality Pedigree (IMQP). Nine novel microsatellite markers within the ∼30-Mb region surrounding the most likely QTL position, including one within the candidate gene calpastatin (CAST), were developed. These markers, along with nine publicly-available markers, were used to perform linkage and haplotype analyses within the IMQP. Within-family linkage analyses revealed at least two families segregating for a highly-significant QTL in strong positional agreement with CAST. A combined analysis of these two families yielded QTL intervals of 36 cM and 7 cM for Instron shear force and taste panel tenderness, respectively, while haplotype analyses suggested further refinement to a 1.8 cM interval containing CAST. To identify allelic variation that may influence pork tenderness, the complete genomic sequence of porcine CAST was determined. Nearly 77.6% of this gene was then re-sequenced from each of six IMQP F1 boars. Based on heterozygosity, 393 of 896 discovered polymorphisms appeared concordant with previous QTL data. The location of this variation within the CAST gene suggests that a causative mutation is likely to be regulatory. Functional characterization of CAST variation should enhance understanding of the molecular basis of pork tenderness, and thus allow for genetic improvement of pork products. The effectiveness of CAST polymorphisms for marker-assisted selection (MAS) of pork tenderness can now be assessed. Furthermore, genomic resources developed in this study may be used to investigate many other porcine QTL, including additional tenderness QTL suggested on SSC2q.Made available in DSpace on 2015-09-25T21:08:26Z (GMT). No. of bitstreams: 3
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Transcriptional variation in muscle from cattle with alternative NCAPG/LCORL QTL genotypes
Get PDFThe NCAPG/LCORL locus is a major QTL on bovine chromosome 6 (BTA6) that influences growth and composition in cattle. Genetic variation at this locus is associated with alterations in the developmental program of individuals throughout life that may be detected through transcriptional variation. Here, we propose to characterize how the landscape of transcriptomes differ between individuals with alternative NCAPG/LCORL haplotypes/genotypes. Charolais calves (n=804) were genotyped using the Illumina® BovSNP50 BeadChip and their sires (n=38) were genotyped with the BovineHD BeadChip. Additionally, 53 calves were genotyped on the BovineHD BeadChip (770k) platform for use in further analyses. The 38 sires and 53 calves genotyped on the 770k platform were used to impute the calf genotypes, resulting in approximately 638,230 markers per individual used for GWAS analyses. Twenty-four animals were selected based on alternative homozygous NCAPG/LCORL haplotypes/genotypes (i.e. 12 “QQ” and 12 “qq”, where “Q” is the QTL allele associated with increased birth weight and “q” the alternative allele) and a muscle biopsy was taken from each animal at 300 days of age. Total RNA was isolated and used for NGS library construction and libraries were sequenced on a HiSeq2500 using single-end chemistry. Sequencing yielded 898 million reads (average >30 million reads/sample) that were mapped to the bovine reference genome (Build UMD3.1). Differential gene expression was analyzed using edgeR. Five hundred and seven (507) genes were found to be differentially expressed (FDR P-value < 0.01) in QQ compared to qq animals, including LCORL which was upregulated. Network inferring using weighted gene co-expression network analysis (WGCNA) revealed eleven co-expression gene network modules significantly correlated with genotype. Of these, the LCORL containing module (Blue) showed the highest positive correlation. Gene Ontology enrichment analysis and Ingenuity Pathway Analysis (IPA) revealed an up- and downregulation of lean growth and fat synthesis pathways, respectively, associated with our list of differentially expressed genes; additionally, enrichment and activation of growth and metabolism related-pathways was reported for WGCNA Blue module. Our results suggest that LCORL overexpression may be driving increased cellular metabolism and, consequently, lean growth. Additionally, it suggests that LCORL may be part of a larger complex gene network underlying growth and development, and that the overexpression of this gene may influence the expression pattern of other genes in the same network. Our results provide valuable insights into the molecular mechanisms underlying the phenotypic variation between calves with alternative NCAPG/LCORL genotypes. The characterization of these molecular changes will allow us to better understand the regulation of growth and composition in cattle.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-05-01The student, Fernanda Martins Rodrigues, accepted the attached license on 2017-04-26 at 15:21.The student, Fernanda Martins Rodrigues, submitted this Thesis for approval on 2017-04-26 at 15:27.This Thesis was approved for publication on 2017-04-26 at 18:14.DSpace SAF Submission Ingestion Package generated from Vireo submission #11096 on 2017-08-10 at 14:32:43Made available in DSpace on 2017-08-10T19:52:25Z (GMT). No. of bitstreams: 2
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CRISPR/CAS9 mediated gene editing for the improvement of beef and dairy cattle
Get PDFWith the growing demands on agricultural production around the world, it is becoming increasingly important to figure out how to feed the growing population. For thousands of years we have been optimizing our agricultural outputs in livestock species through reproductive selection based on favorable traits, many of which are due to genetic variation. Single nucleotide polymorphisms are responsible for a great deal of either beneficial or undesirable mutations. In this study, we examine how we can use the CRISPR/Cas9 system to induce single-base pair substitutions, thereby improving animal genetics through removal of undesirable or insertion of beneficial mutations. In Angus beef cattle (Bos taurus), a mutation in the NHL-repeat containing 2 gene causes a heritable abnormality referred to as Developmental Duplications (DD). Calves homozygous for this mutation are affected with a broad range of neural tube defects and commonly exhibit polymelia, which is the presence of additional limbs. The mutation has been identified as a single-nucleotide polymorphism resulting in a valine to alanine substitution in a highly conserved protein-coding region of the gene. Similarly, in Holstein dairy cattle (Bos taurus) a guanine to adenine substitution mutation in the α-lactalbumin flanking region at (+15) base pairs from the transcriptional start site has been shown to be associated with increased quantity of milk production, likely due to upregulation of the α-lactalbumin protein and increased lactose synthesis. Other breeds of cattle used for dairy production, such as Nelore and other tropically adapted Bos indicus breeds, do not have this mutation unless they are crossed to Holsteins. In this study, the CRISPR/Cas9 system was paired with a guide RNA targeting the aforementioned genes to create a break in the DNA of fibroblast cells from Nelore and Angus cattle. Cells were also supplied with a 90 nucleotide single stranded-oligonucleotide repair template, which allows for homology directed repair to introduce the desired substitution at those loci. Cells from these cattle that are genetically improved by this technique may be used for somatic cell nuclear transfer and resulting embryos will be transferred to recipients. With these genetic improvements, we can preserve high quality beef cattle genetics while eliminating a harmful mutation, and we can increase milk yield of tropically adapted dairy cattle to feed malnourished populations around the world.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-08-01The student, Kathryn Polkoff, accepted the attached license on 2017-07-14 at 15:54.The student, Kathryn Polkoff, submitted this Thesis for approval on 2017-07-14 at 16:02.This Thesis was approved for publication on 2017-07-19 at 16:45.DSpace SAF Submission Ingestion Package generated from Vireo submission #11476 on 2018-03-02 at 13:02:18Made available in DSpace on 2018-03-02T19:59:42Z (GMT). No. of bitstreams: 2
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Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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