A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy
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{"title"=>"A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy", "type"=>"journal", "authors"=>[{"first_name"=>"Camilla S.", "last_name"=>"Bruun", "scopus_author_id"=>"24074240400"}, {"first_name"=>"Karin H.", "last_name"=>"Jäderlund", "scopus_author_id"=>"6506797605"}, {"first_name"=>"Mette", "last_name"=>"Berendt", "scopus_author_id"=>"7003634339"}, {"first_name"=>"Kristine B.", "last_name"=>"Jensen", "scopus_author_id"=>"57199368882"}, {"first_name"=>"Eva H.", "last_name"=>"Spodsberg", "scopus_author_id"=>"55321977800"}, {"first_name"=>"Hanne", "last_name"=>"Gredal", "scopus_author_id"=>"6506657344"}, {"first_name"=>"G. Diane", "last_name"=>"Shelton", "scopus_author_id"=>"7004309822"}, {"first_name"=>"James R.", "last_name"=>"Mickelson", "scopus_author_id"=>"7005706639"}, {"first_name"=>"Katie M.", "last_name"=>"Minor", "scopus_author_id"=>"24824847700"}, {"first_name"=>"Hannes", "last_name"=>"Lohi", "scopus_author_id"=>"6602309083"}, {"first_name"=>"Inge", "last_name"=>"Bjerkås", "scopus_author_id"=>"6603806098"}, {"first_name"=>"Øyvind", "last_name"=>"Stigen", "scopus_author_id"=>"6603414562"}, {"first_name"=>"Arild", "last_name"=>"Espenes", "scopus_author_id"=>"6602467989"}, {"first_name"=>"Cecilia", "last_name"=>"Rohdin", "scopus_author_id"=>"35574652400"}, {"first_name"=>"Rebecca", "last_name"=>"Edlund", "scopus_author_id"=>"55583739000"}, {"first_name"=>"Jennie", "last_name"=>"Ohlsson", "scopus_author_id"=>"55583731600"}, {"first_name"=>"Sigitas", "last_name"=>"Cizinauskas", "scopus_author_id"=>"6603691893"}, {"first_name"=>"Páll S.", "last_name"=>"Leifsson", "scopus_author_id"=>"6603401545"}, {"first_name"=>"Cord", "last_name"=>"Drögemüller", "scopus_author_id"=>"7005041360"}, {"first_name"=>"Lars", "last_name"=>"Moe", "scopus_author_id"=>"7003831711"}, {"first_name"=>"Susanna", "last_name"=>"Cirera", "scopus_author_id"=>"6603117934"}, {"first_name"=>"Merete", "last_name"=>"Fredholm", "scopus_author_id"=>"7003481985"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368294467", "sgr"=>"84873511599", "issn"=>"19326203", "pmid"=>"23393557", "scopus"=>"2-s2.0-84873511599", "doi"=>"10.1371/journal.pone.0054547", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)"}, "id"=>"0f719a38-5b34-31c3-8996-7794e74887a3", "abstract"=>"The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (NDRG1) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution. This substitution was categorized to be \"probably damaging\" to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can now be used to eliminate the disease in Alaskan Malamutes.", "link"=>"http://www.mendeley.com/research/gly98val-mutation-nmyc-downstream-regulated-gene-1-ndrg1-alaskan-malamutes-polyneuropathy", "reader_count"=>28, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Librarian"=>2, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>2, "Other"=>7, "Student > Bachelor"=>1, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Librarian"=>2, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>2, "Other"=>7, "Student > Bachelor"=>1, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>5, "Neuroscience"=>1, "Veterinary Science and Veterinary Medicine"=>10, "Social Sciences"=>1, "Computer Science"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Computer Science"=>{"Computer Science"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>10}}, "reader_count_by_country"=>{"United States"=>1, "Finland"=>1, "Spain"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/482481"], "description"=>"<div><p>The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (<em>NDRG1</em>) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the <em>NDRG1</em> gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a <em>Gly98Val</em> amino acid substitution. This substitution was categorized to be “probably damaging” to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can now be used to eliminate the disease in Alaskan Malamutes.</p> </div>", "links"=>[], "tags"=>["mutation", "n-myc", "downstream", "regulated", "alaskan", "malamutes", "polyneuropathy"], "article_id"=>155830, "categories"=>["Cell Biology", "Neuroscience", "Genetics"], "users"=>["Camilla S. Bruun", "Karin H. Jäderlund", "Mette Berendt", "Kristine B. Jensen", "Eva H. Spodsberg", "Hanne Gredal", "G. Diane Shelton", "James R. Mickelson", "Katie M. Minor", "Hannes Lohi", "Inge Bjerkås", "Øyvind Stigen", "Arild Espenes", "Cecilia Rohdin", "Rebecca Edlund", "Jennie Ohlsson", "Sigitas Cizinauskas", "Pall S. Leifsson", "Cord Drögemüller", "Lars Moe", "Susanna Cirera", "Merete Fredholm"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054547"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Gly98Val_Mutation_in_the_N_Myc_Downstream_Regulated_Gene_1_NDRG1_in_Alaskan_Malamutes_with_Polyneuropathy__/155830", "title"=>"A <em>Gly98Val</em> Mutation in the N-Myc Downstream Regulated Gene 1 (<em>NDRG1</em>) in Alaskan Malamutes with Polyneuropathy", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-05 01:37:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/494910"], "description"=>"<p>Representative cranial tibial muscle and peroneal nerve biopsy transverse sections from a two year old female Alaskan Malamute (a,b) and a three year old female Alaskan Malamute (c,d) with histopathological findings consistent with polyneuropathy. Large and small groups of atrophic fibers were present with variable severity and fatty infiltration (a,c. H&E stain). A moderate to marked depletion of myelinated fibers was evident in resin embedded nerve biopsy sections (b,d. Toluidine blue stain). Nerve fiber loss resulted from chronic axonal degeneration (arrows in b,d).</p>", "links"=>[], "tags"=>["peripheral", "pathology", "alaskan", "malamutes", "polyneuropathy", "mutation"], "article_id"=>165391, "categories"=>["Cell Biology", "Neuroscience", "Genetics"], "users"=>["Camilla S. Bruun", "Karin H. Jäderlund", "Mette Berendt", "Kristine B. Jensen", "Eva H. Spodsberg", "Hanne Gredal", "G. Diane Shelton", "James R. Mickelson", "Katie M. Minor", "Hannes Lohi", "Inge Bjerkås", "Øyvind Stigen", "Arild Espenes", "Cecilia Rohdin", "Rebecca Edlund", "Jennie Ohlsson", "Sigitas Cizinauskas", "Pall S. Leifsson", "Cord Drögemüller", "Lars Moe", "Susanna Cirera", "Merete Fredholm"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054547.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Muscle_and_peripheral_nerve_pathology_in_Alaskan_Malamutes_with_polyneuropathy_and_a_mutation_in_NDRG1_/165391", "title"=>"Muscle and peripheral nerve pathology in Alaskan Malamutes with polyneuropathy and a mutation in NDRG1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-05 01:29:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/495150"], "description"=>"<p>Alignment of NDRG1 protein sequences from five mammalian species: Homo sapiens, Pan troglodytes, Canis lupus, Bos taurus and Mus musculus shows a sequence similarity of 94.7%. Residue 98 (gly, marked with a frame) which is substituted in Alaskan Malamutes with the G>T mutation, is conserved in the five species.</p>", "links"=>[], "tags"=>["alignment", "mammalian", "ndrg1"], "article_id"=>165631, "categories"=>["Cell Biology", "Neuroscience", "Genetics"], "users"=>["Camilla S. Bruun", "Karin H. Jäderlund", "Mette Berendt", "Kristine B. Jensen", "Eva H. Spodsberg", "Hanne Gredal", "G. Diane Shelton", "James R. Mickelson", "Katie M. Minor", "Hannes Lohi", "Inge Bjerkås", "Øyvind Stigen", "Arild Espenes", "Cecilia Rohdin", "Rebecca Edlund", "Jennie Ohlsson", "Sigitas Cizinauskas", "Pall S. Leifsson", "Cord Drögemüller", "Lars Moe", "Susanna Cirera", "Merete Fredholm"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054547.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multiple_alignment_of_mammalian_NDRG1_proteins_/165631", "title"=>"Multiple alignment of mammalian NDRG1 proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-05 01:33:51"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Behavior", "average_usage"=>[306, 490, 611, 718, 817, 916, 999, 1091, 1185, 1258, 1341, 1412, 1476]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Zoology", "average_usage"=>[294, 473, 591, 693, 788, 883, 972, 1054, 1140, 1222, 1299, 1381, 1446]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}]}
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