Christian Bendixen

Aarhus University, Aarhus, Central Jutland, Denmark

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Publications (163)532.65 Total impact

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    ABSTRACT: Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13. Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4, to be associated with F4ab/ac susceptibility.
    Animal Genetics 10/2009; 41(1):21-5. DOI:10.1111/j.1365-2052.2009.01952.x · 2.21 Impact Factor
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    ABSTRACT: The control of fecundity is critical in determining mammalian offspring survival. It is regulated principally by the ovulation rate, so that primates and large farm species commonly have a single offspring. Previously, several mutations have been identified in sheep which increase the naturally low ovulation rate; although in some cases homozygous ewes are infertile. In the present study we present a detailed characterization of a novel mutation in growth differentiation factor 9 (GDF9), found in Icelandic Thoka sheep. This mutation is a single base change (A1279C) resulting in a nonconservative amino acid change (S109R) in the C-terminus of the mature GDF9 protein, which is normally expressed in oocytes at all stages of development. Genotyping all animals for which reproductive records were available confirmed this mutation to be associated with increased fecundity in heterozygous ewes and infertility in homozygotes. Analysis of homozygote ovarian morphology and a number of genes normally activated in growing follicles showed that GDF9 was not involved in oocyte activation, but in subsequent development of the follicle. This study highlights the importance of oocyte factors in regulating fertility and provides new information for structural analysis and investigation of the potentially important sites of dimerization or translational modifications required to produce biologically active GDF9. It also provides the basis for the utilization of these animals to enhance sheep production.
    Reproduction 09/2009; 138(6):921-33. DOI:10.1530/REP-09-0193
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    ABSTRACT: The driving force behind the transition from a foraging to a farming lifestyle in prehistoric Europe (Neolithization) has been debated for more than a century [1-3]. Of particular interest is whether population replacement or cultural exchange was responsible [3-5]. Scandinavia holds a unique place in this debate, for it maintained one of the last major hunter-gatherer complexes in Neolithic Europe, the Pitted Ware culture [6]. Intriguingly, these late hunter-gatherers existed in parallel to early farmers for more than a millennium before they vanished some 4,000 years ago [7, 8]. The prolonged coexistence of the two cultures in Scandinavia has been cited as an argument against population replacement between the Mesolithic and the present [7, 8]. Through analysis of DNA extracted from ancient Scandinavian human remains, we show that people of the Pitted Ware culture were not the direct ancestors of modern Scandinavians (including the Saami people of northern Scandinavia) but are more closely related to contemporary populations of the eastern Baltic region. Our findings support hypotheses arising from archaeological analyses that propose a Neolithic or post-Neolithic population replacement in Scandinavia [7]. Furthermore, our data are consistent with the view that the eastern Baltic represents a genetic refugia for some of the European hunter-gatherer populations.
    Current biology: CB 09/2009; 19(20):1758-62. DOI:10.1016/j.cub.2009.09.017 · 9.92 Impact Factor
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    ABSTRACT: Bovine spinal dysmyelination (BSD) is a recessive congenital neurodegenerative disease in cattle (Bos taurus) characterized by pathological changes of the myelin sheaths in the spinal cord. The occurrence of BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. Here, we show that the disease locus on bovine chromosome 11 harbors the SPAST gene that, when mutated, is responsible for the human disorder hereditary spastic paraplegia (HSP). Initially, SPAST encoding Spastin was considered a less likely candidate gene for BSD since the modes of inheritance as well as the time of onset and severity of symptoms differ widely between HSP and BSD. However, sequence analysis of the bovine SPAST gene in affected animals identified a R560Q substitution at a position in the ATPase domain of the Spastin protein that is invariant from insects to mammals. Interestingly, three different mutations in human SPAST gene at the equivalent position are known to cause HSP. To explore this observation further, we genotyped more than 3,100 animals of various cattle breeds and found that the glutamine allele exclusively occurred in breeds upgraded with ABS. Furthermore, all confirmed BSD carriers were heterozygous, while all affected calves were homozygous for the glutamine allele consistent with recessive transmission of the underlying mutation and complete penetrance in the homozygous state. Subsequent analysis of recombinant Spastin in vitro showed that the R560Q substitution severely impaired the ATPase activity, demonstrating a causal relationship between the SPAST mutation and BSD.
    Neurogenetics 09/2009; 11(2):175-83. DOI:10.1007/s10048-009-0214-0 · 2.66 Impact Factor
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    ABSTRACT: Boar taint is an unpleasant odour and flavour of the meat from some uncastrated male pigs primarily caused by elevated levels of androstenone and skatole in adipose tissue. Androstenone is produced in the same biochemical pathway as testosterone and estrogens, which represents a particular challenge when selecting against high levels of androstenone in the breeding programme, without simultaneously decreasing levels of other steroids. Detection of single nucleotide polymorphisms (SNPs) associated with compounds affecting boar taint is important both for gaining a better understanding of the complex regulation of the trait and for the purpose of identifying markers that can be used to improve the gain of breeding. The beneficial SNPs to be used in breeding would have the combinational effects of reducing levels of boar taint without affecting fertility of the animals. The aim of this study was to detect SNPs in boar taint candidate genes and to perform association studies for both single SNPs and haplotypes with levels of boar taint compounds and phenotypes related to reproduction. An association study involving 275 SNPs in 121 genes and compounds related to boar taint and reproduction were carried out in Duroc and Norwegian Landrace boars. Phenotypes investigated were levels of androstenone, skatole and indole in adipose tissue, levels of androstenone, testosterone, estrone sulphate and 17beta-estradiol in plasma, and length of bulbo urethralis gland. The SNPs were genotyped in more than 2800 individuals and several SNPs were found to be significantly (LRT > 5.4) associated with the different phenotypes. Genes with significant SNPs in either of the traits investigated include cytochrome P450 members CYP2E1, CYP21, CYP2D6 and CYP2C49, steroid 5alpha-reductase SRD5A2, nuclear receptor NGFIB, catenin CTNND1, BRCA1 associated protein BAP1 and hyaluronoglucosaminidase HYAL2. Haplotype analysis provided additional evidence for an effect of CYP2E1 on levels of skatole and indole, and for BAP1, HYAL2 and SRD5A2 on levels of androstenone. The findings in this study indicate that polymorphisms in CYP2E1, CYP21, CYP2D6, CYP2C49, NGFIB and CTNND1 might be used to reduce levels of boar taint without affecting levels of testosterone, estrone sulphate, 17beta-estradiol or length of bulbo urethralis gland.
    BMC Genetics 08/2009; 10:32. DOI:10.1186/1471-2156-10-32 · 2.36 Impact Factor
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    ABSTRACT: The European bison (Bison bonasus) has recovered successfully after a severe bottleneck about 90 years ago but has been left with low genetic variability that may substantially hinder parentage and identity analysis. According to pedigree analysis, over 80% of the genes in the contemporary population descend from just two founder animals and inbreeding coefficients averaged almost 0.5, whereas microsatellite heterozygosity does not exceed 0.3. We present a comparison of the effectiveness of 17 microsatellite and 960 single nucleotide polymorphism (SNP) markers for paternity and identity analysis in the European bison. Microsatellite-based paternity and identity analysis was unsuccessful because of low marker heterozygosity and is not a practical approach in this species. Simulations using SNP markers suggest that 80-90 randomly selected loci, or just 50-60 of the most heterozygous loci, would be sufficient to ensure successful paternity and identity analysis in this species. For the purpose of standardizing future analysis, a panel of 50-60 bovine SNPs characterized by high heterozygosity and an even distribution in the genome could be selected. This panel of markers could be typed using VeraCode (Illumina) or similar SNP genotyping systems. The low cost of these SNP genotyping methods compared with a 16 locus microsatellite survey means that off-the-shelf SNP genotyping systems developed for domestic species represent powerful tools for genetic analysis in related species, and can be effective even in bottlenecked species in which heterozygosity of other markers such as microsatellites may be very low.
    Heredity 08/2009; 103(4):326-32. DOI:10.1038/hdy.2009.73 · 3.80 Impact Factor
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    ABSTRACT: Alpha-synuclein is the main constituent of Lewy bodies in familial and sporadic cases of Parkinson's disease (PD). Autosomal dominant point mutations, gene duplications or triplications in the alpha-synuclein (SNCA) gene cause hereditary forms of PD. One of the alpha-synuclein point mutations, Ala53Thr, is associated with increased oligomerization toxicity leading to familial early-onset PD in humans. The amino acid in position 53 in alpha-synuclein is an alanine in humans, great apes and Old World primates. However, this amino acid is a threonine in the alpha-synuclein of all other examined species, including New World monkeys. Here, we present DNA sequence analysis of SNCA and the deduced amino acid sequences of alpha-synuclein cloned from various different species, ranging from fish to mammals, which are known for their long-living potential. In all these investigated species the 53Thr is found. We conclude that 53Thr is not a molecular adaptation for long-living animals to minimize the risk of developing PD.
    Biochemical and Biophysical Research Communications 08/2009; 387(3):602-5. DOI:10.1016/j.bbrc.2009.07.070 · 2.28 Impact Factor
  • Biochemical Genetics 08/2009; 47(11-12):812-6. DOI:10.1007/s10528-009-9279-6 · 0.82 Impact Factor
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    ABSTRACT: The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein and gamma-synuclein. beta-Synuclein inhibits the aggregation of alpha-synuclein, a protein involved in Parkinson's disease. We have cloned and characterized the cDNA sequence for porcine beta-synuclein (SNCB) from pig cerebellum using RT-PCR. Expression analysis by quantitative RT-PCR demonstrated that SNCB transcripts were highly abundant in brain tissues. SNCB mRNA was also detected early in embryogenesis and significant increases in transcript levels were observed in several brain tissues during embryo development. Radiation hybrid mapping data indicate that the porcine SNCB maps to the q arm of chromosome 2 (2q21-22). The subcellular localization of recombinant porcine beta-synuclein was determined in three different cell types and shown to be cytoplasmic.
    Molecular Biology Reports 05/2009; 37(3):1439-49. DOI:10.1007/s11033-009-9531-5 · 1.96 Impact Factor
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    ABSTRACT: Genetic linkage maps are necessary for mapping of mendelian traits and quantitative trait loci (QTLs). To identify the actual genes, which control these traits, a map based on gene-associated single nucleotide polymorphism (SNP) markers is highly valuable. In this study, the SNPs were genotyped in a large family material comprising more than 5,000 piglets derived from 12 Duroc boars crossed with 236 Danish Landrace/Danish Large White sows. The SNPs were identified in sequence alignments of 4,600 different amplicons obtained from the 12 boars and containing coding regions of genes derived from expressed sequence tags (ESTs) and genomic shotgun sequences. Linkage maps of all 18 porcine autosomes were constructed based on 456 gene-associated and six porcine EST-based SNPs. The total length of the averaged-sex whole porcine autosome was estimated to 1,711.8 cM resulting in an average SNP spacing of 3.94 cM. The female and male maps were estimated to 2,336.1 and 1,441.5 cM, respectively. The gene order was validated through comparisons to the cytogenetic and/or physical location of 203 genes, linkage to evenly spaced microsatellite markers as well as previously reported conserved synteny. A total of 330 previously unmapped genes and ESTs were mapped to the porcine autosome while ten genes were mapped to unexpected locations. The linkage map presented here shows high accuracy in gene order. The pedigree family network as well as the large amount of meiotic events provide good reliability and make this map suitable for QTL and association studies. In addition, the linkage to the RH-map of microsatellites makes it suitable for comparison to other QTL studies.
    BMC Genomics 04/2009; 10:134. DOI:10.1186/1471-2164-10-134 · 4.04 Impact Factor
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    ABSTRACT: The recent development within high-throughput technologies for expression profiling has allowed for parallel analysis of transcriptomes and proteomes in biological systems such as comparative analysis of transcript and protein levels of tissue regulated genes. Until now, such studies of have only included microarray or short length sequence tags for transcript profiling. Furthermore, most comparisons of transcript and protein levels have been based on absolute expression values from within the same tissue and not relative expression values based on tissue ratios. Presented here is a novel study of two porcine tissues based on integrative analysis of data from expression profiling of identical samples using cDNA microarray, 454-sequencing and iTRAQ-based proteomics. Sequence homology identified 2.541 unique transcripts that are detectable by both microarray hybridizations and 454-sequencing of 1.2 million cDNA tags. Both transcript-based technologies showed high reproducibility between sample replicates of the same tissue, but the correlation across these two technologies was modest. Thousands of genes being differentially expressed were identified with microarray. Out of the 306 differentially expressed genes, identified by 454-sequencing, 198 (65%) were also found by microarray. The relationship between the regulation of transcript and protein levels was analyzed by integrating iTRAQ-based proteomics data. Protein expression ratios were determined for 354 genes, of which 148 could be mapped to both microarray and 454-sequencing data. A comparison of the expression ratios from the three technologies revealed that differences in transcript and protein levels across heart and muscle tissues are positively correlated. We show that the reproducibility within cDNA microarray and 454-sequencing is high, but that the agreement across these two technologies is modest. We demonstrate that the regulation of transcript and protein levels across identical tissue samples is positively correlated when the tissue expression ratios are used for comparison. The results presented are of interest in systems biology research in terms of integration and analysis of high-throughput expression data from mammalian tissues.
    BMC Genomics 02/2009; 10:30. DOI:10.1186/1471-2164-10-30 · 4.04 Impact Factor
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    ABSTRACT: The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay. A total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274. Overall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs.
    PLoS ONE 02/2009; 4(8):e6524. DOI:10.1371/journal.pone.0006524 · 3.53 Impact Factor
  • SGLPGE (Statistical genetics of livestock for the post-genomic era) Symposium, University of Wisconsin-Madison, USA; 01/2009
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    ABSTRACT: The TOR1A (also named DYT1) gene encodes a protein, TorsinA, a member of the AAA+ superfamily of ATPases. The AAA+ proteins have diverse functions such as organelle biogenesis, proteosome function, chaperone function, membrane trafficking and microtubule regulation. However, the molecular function of TorsinA is still largely unknown. Mutations in the TOR1A gene, primarily a 3-bp (GAG) deletion are associated with early-onset autosomal dominant torsion dystonia. Animal models may help to provide information about the underlying cellular and molecular mechanism of early-onset generalized dystonia. The close anatomical, physiological, genetic and biochemical resemblance between man and pig suggest that this animal may constitute an excellent model for this disease. This work reports the cloning and analysis of the porcine (Sus scrofa) homologue of TOR1A. Two porcine TOR1A cDNAs were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), using oligonucleotide primers derived from in silico sequences. The porcine TOR1A cDNAs both encode a protein of 333 amino acids which shows a very high similarity to human (92%) TorsinA. Protein structure comparison of human and porcine TorsinA sequences revealed that there were few differences in the amino acid sequences between the two species and these are not likely to alter TorsinA structure and function. Quantitative real-time RT-PCR detection exhibited TOR1A mRNA expression in all analyzed porcine tissues, although at different levels. The TOR1A gene was demonstrated to be localized on porcine chromosome 1. Single nucleotide polymorphism (SNP) analysis revealed several SNPs in the porcine TOR1A gene, both in the coding region and also in the 3' UTR region. Overexpression of mutant (DeltaE303-304) porcine TorsinA in neuroblastoma cells leads to a more perinuclear localization compared with a cytoplasmatic localization for wildtype TorsinA. Furthermore, inclusion-like structures were observed. In conclusion, the results obtained for porcine TOR1A suggest that the pig could be an ideal model for early-onset generalized dystonia.
    Gene 12/2008; 430(1-2):105-15. DOI:10.1016/j.gene.2008.10.023 · 2.08 Impact Factor
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    ABSTRACT: The aim of this study was to 1) detect QTL across the cattle genome that influence the incidence of clinical mastitis and somatic cell score (SCS) in Danish Holsteins, and 2) characterize these QTL for pleiotropy versus multiple linked quantitative trait loci (QTL) when chromosomal regions affecting clinical mastitis were also affecting other traits in the Danish udder health index or milk production traits. The chromosomes were scanned using a granddaughter design where markers were typed for 19 to 34 grandsire families and 1,373 to 2,042 sons. A total of 356 microsatellites covering all 29 autosomes were used in the scan. Among the across-family regression analyses, 16 showed chromosome-wide significance for the primary traits incidence of clinical mastitis in first (CM1), second (CM2), and third (CM3) lactations, and SCS. Regions of chromosomes 5, 6, 9, 11, 15, and 26 were found to affect CM and regions of chromosomes 5, 6, 8, 13, 22, 23, 24, and 25 affected SCS. Markers on chromosomes 6, 11, 15, and 26 can be used to perform marker-assisted selection on CM without a direct negative selection on milk yield, because no effects were detected on the milk traits. Comparing multi-trait models assuming either a pleiotropic QTL affecting 2 traits or 2 QTL each affecting 1 trait gave some evidence to distinguish between these models. For Bos taurus autosome 5, the most likely models were a pleiotropic QTL affecting CM2, CM3, and SCS, and a linked QTL affecting fat yield index. For Bos taurus autosome 9, the most likely model is a pleiotropic QTL affecting CM1 and CM2 at approximately 8 cM.
    Journal of Dairy Science 11/2008; 91(10):4028-36. DOI:10.3168/jds.2007-0290 · 2.55 Impact Factor
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    ABSTRACT: Boar taint is the unpleasant odour and flavour of the meat of uncastrated male pigs that is primarily caused by high levels of androstenone and skatole in adipose tissue. Androstenone is a steroid and its levels are mainly genetically determined. Studies on androstenone metabolism have, however, focused on a limited number of genes. Identification of additional genes influencing levels of androstenone may facilitate implementation of marker assisted breeding practices. In this study, microarrays were used to identify differentially expressed genes and pathways related to androstenone metabolism in the liver from boars with extreme levels of androstenone in adipose tissue. Liver tissue samples from 58 boars of the two breeds Duroc and Norwegian Landrace, 29 with extreme high and 29 with extreme low levels of androstenone, were selected from more than 2500 individuals. The samples were hybridised to porcine cDNA microarrays and the 1% most significant differentially expressed genes were considered significant. Among the differentially expressed genes were metabolic phase I related genes belonging to the cytochrome P450 family and the flavin-containing monooxygenase FMO1. Additionally, phase II conjugation genes including UDP-glucuronosyltransferases UGT1A5, UGT2A1 and UGT2B15, sulfotransferase STE, N-acetyltransferase NAT12 and glutathione S-transferase were identified. Phase I and phase II metabolic reactions increase the water solubility of steroids and play a key role in their elimination. Differential expression was also found for genes encoding 17beta-hydroxysteroid dehydrogenases (HSD17B2, HSD17B4, HSD17B11 and HSD17B13) and plasma proteins alpha-1-acid glycoprotein (AGP) and orosomucoid (ORM1). 17beta-hydroxysteroid dehydrogenases and plasma proteins regulate the availability of steroids by controlling the amount of active steroids accessible to receptors and available for metabolism. Differences in the expression of FMO1, NAT12, HSD17B2 and HSD17B13 were verified by quantitative real competitive PCR. A number of genes and pathways related to metabolism of androstenone in liver were identified, including new candidate genes involved in phase I oxidation metabolism, phase II conjugation metabolism, and regulation of steroid availability. The study is a first step towards a deeper understanding of enzymes and regulators involved in pathways of androstenone metabolism and may ultimately lead to the discovery of markers to reduce boar taint.
    BMC Veterinary Research 09/2008; 4(1):29. DOI:10.1186/1746-6148-4-29 · 1.74 Impact Factor
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    European Association of Animal Production (EAAP), Vilnius, Lithuania; 08/2008
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    ABSTRACT: The Paleo-Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New World's northern extremes. However, their origin and genetic relationship to later cultures are unknown. We sequenced a mitochondrial genome from a Paleo-Eskimo human by using 3400-to 4500-year-old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo-Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This result suggests that the earliest migrants into the New World's northern extremes derived from populations in the Bering Sea area and were not directly related to Native Americans or the later Neo-Eskimos that replaced them.
    Science 07/2008; 320(5884):1787-9. DOI:10.1126/science.1159750 · 31.48 Impact Factor
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    ABSTRACT: The gamma-synuclein protein is involved in breast carcinogenesis and has also been implicated in other forms of cancer and in ocular diseases. Furthermore, gamma-synuclein is believed to have a role in certain neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. This work reports the cloning and characterization of the porcine (Sus scrofa) gamma-synuclein cDNA (SNCG). The SNCG cDNA was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) using oligonucleotide primers derived from in silico sequences. The porcine SNCG cDNA codes for a protein of 126 amino acids which shows a high similarity to bovine (90%), human (87%) and mouse (83%) gamma-synuclein. A genomic clone containing the entire porcine SNCG gene was isolated and its genomic organization determined. The gene is composed of five exons, the general structure being observed to be very similar to that of the human SNCG gene. Expression analysis by quantitative real-time RT-PCR revealed the presence of SNCG transcripts in all examined organs and tissues. Differential expression was observed, with very high levels of SNCG mRNA in fat tissue and high expression levels in spleen, cerebellum, frontal cortex and pituitary gland. Expression analysis also showed that porcine SNCG transcripts could be detected in different brain regions during early stages of embryo development. The porcine SNCG orthologue was mapped to chromosome 14q25-q29. The distribution of recombinant porcine gamma-synuclein was studied in three different transfected cell lines and the protein was found to be predominantly localized in the cytoplasm.
    Molecular Biology Reports 06/2008; 36(5):971-9. DOI:10.1007/s11033-008-9270-z · 1.96 Impact Factor
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    ABSTRACT: After parenchymal loss, the liver regenerates restoring normal mass and metabolic function. Prevailing theories on triggering events leading to regeneration include humoral, metabolic, and flow-mediated mechanisms, the latter emphasizing the importance of shear stress mediated nitric oxide regulation. We aimed to investigate whether the grade of resection and hence the portal venous pressure and sinusoidal shear stress increase would be reflected in the gene expression profiles in the liver remnant by using a global porcine cDNA microarray chip with approximately 23,000 genes represented. Six pig livers were resected with 62% (low portal pressure resection) and 75% (high portal pressure resection), resulting in a portal venous pressure increase from a baseline of 6.1-8.2 and 12 mmHg, respectively. By sampling consecutive biopsies from the liver remnants, we found differentially expressed genes in the high portal pressure resection group to have functions related primarily to apoptosis, nitric oxide metabolism and oxidative stress, whereas differentially expressed genes in the low portal pressure resection group potentially regulate the cell cycle. Common to both groups was the upregulation of genes regulating inflammation, transport, cell proliferation, development, and protein metabolism. Also common to both groups was both up- and downregulation of genes regulating cell-cell signaling, signal transduction, cell adhesion, and translation. Genes regulating the metabolism of lipids, hormones, amines, and alcohol were downregulated in both groups. In conclusion, the genetic regenerative response in the liver remnant to varies according to the level of resection.
    AJP Gastrointestinal and Liver Physiology 04/2008; 294(3):G819-30. DOI:10.1152/ajpgi.00179.2007 · 3.74 Impact Factor

Publication Stats

4k Citations
532.65 Total Impact Points

Institutions

  • 1990–2014
    • Aarhus University
      • • Department of Molecular Biology and Genetics
      • • Department of Genetics and Biotechnology
      Aarhus, Central Jutland, Denmark
  • 2007
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 2004
    • Royal Agricultural University
      Cicester, England, United Kingdom
  • 2001
    • Masaryk University
      Brünn, South Moravian, Czech Republic
  • 1994–1996
    • Columbia University
      • Department of Genetics and Development
      New York City, NY, United States