A Mutation in the FAM83G Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)
Publication Date
May 15, 2014
Journal
PLOS Genetics
Authors
Michaela Drögemüller, Vidhya Jagannathan, Doreen Becker, Cord Drögemüller, et al
Volume
10
Issue
5
Pages
e1004370
DOI
https://dx.plos.org/10.1371/journal.pgen.1004370
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1004370
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24832243
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022470
Europe PMC
http://europepmc.org/abstract/MED/24832243
Web of Science
000337145100059
Scopus
84901615925
Mendeley
http://www.mendeley.com/research/mutation-fam83g-gene-dogs-hereditary-footpad-hyperkeratosis-hfh
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Mendeley | Further Information

{"title"=>"A Mutation in the FAM83G Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)", "type"=>"journal", "authors"=>[{"first_name"=>"Michaela", "last_name"=>"Drögemüller", "scopus_author_id"=>"6507424400"}, {"first_name"=>"Vidhya", "last_name"=>"Jagannathan", "scopus_author_id"=>"7006778326"}, {"first_name"=>"Doreen", "last_name"=>"Becker", "scopus_author_id"=>"35077480900"}, {"first_name"=>"Cord", "last_name"=>"Drögemüller", "scopus_author_id"=>"7005041360"}, {"first_name"=>"Claude", "last_name"=>"Schelling", "scopus_author_id"=>"7006135657"}, {"first_name"=>"Jocelyn", "last_name"=>"Plassais", "scopus_author_id"=>"55433952500"}, {"first_name"=>"Cécile", "last_name"=>"Kaerle", "scopus_author_id"=>"56184527400"}, {"first_name"=>"Caroline", "last_name"=>"Dufaure de Citres", "scopus_author_id"=>"55875868200"}, {"first_name"=>"Anne", "last_name"=>"Thomas", "scopus_author_id"=>"19436643300"}, {"first_name"=>"Eliane J.", "last_name"=>"Müller", "scopus_author_id"=>"7402776037"}, {"first_name"=>"Monika M.", "last_name"=>"Welle", "scopus_author_id"=>"35997457800"}, {"first_name"=>"Petra", "last_name"=>"Roosje", "scopus_author_id"=>"6701755423"}, {"first_name"=>"Tosso", "last_name"=>"Leeb", "scopus_author_id"=>"7006758115"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"24832243", "doi"=>"10.1371/journal.pgen.1004370", "sgr"=>"84901615925", "scopus"=>"2-s2.0-84901615925", "issn"=>"15537404", "pui"=>"373197054"}, "id"=>"0662a392-fe4b-381a-aab5-3c10f17feab0", "abstract"=>"Hereditary footpad hyperkeratosis (HFH) represents a palmoplantar hyperkeratosis, which is inherited as a monogenic autosomal recessive trait in several dog breeds, such as e.g. Kromfohrländer and Irish Terriers. We performed genome-wide association studies (GWAS) in both breeds. In Kromfohrländer we obtained a single strong association signal on chromosome 5 (praw = 1.0×10-13) using 13 HFH cases and 29 controls. The association signal replicated in an independent cohort of Irish Terriers with 10 cases and 21 controls (praw = 6.9×10-10). The analysis of shared haplotypes among the combined Kromfohrländer and Irish Terrier cases defined a critical interval of 611 kb with 13 predicted genes. We re-sequenced the genome of one affected Kromfohrländer at 23.5× coverage. The comparison of the sequence data with 46 genomes of non-affected dogs from other breeds revealed a single private non-synonymous variant in the critical interval with respect to the reference genome assembly. The variant is a missense variant (c.155G>C) in the FAM83G gene encoding a protein with largely unknown function. It is predicted to change an evolutionary conserved arginine into a proline residue (p.R52P). We genotyped this variant in a larger cohort of dogs and found perfect association with the HFH phenotype. We further studied the clinical and histopathological alterations in the epidermis in vivo. Affected dogs show a moderate to severe orthokeratotic hyperplasia of the palmoplantar epidermis. Thus, our data provide the first evidence that FAM83G has an essential role for maintaining the integrity of the palmoplantar epidermis.", "link"=>"http://www.mendeley.com/research/mutation-fam83g-gene-dogs-hereditary-footpad-hyperkeratosis-hfh", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>3, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>3, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>2, "Veterinary Science and Veterinary Medicine"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>3}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1499090"], "description"=>"a<p>The sequences were compared to the reference genome (CanFam 3.1) from a Boxer. Only variants that were homozygous in the affected Kromfohrländer are reported.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "genome", "re-sequencing", "affected"], "article_id"=>1027902, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.t001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Variants_detected_by_whole_genome_re_sequencing_of_an_affected_Kromfohrl_228_nder_/1027902", "title"=>"Variants detected by whole genome re-sequencing of an affected Kromfohrländer.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499087"], "description"=>"<p>(A) Paw of a 1 year old affected Kromfohrländer. Note the cracked surface and deep fissures of the foot pads. (B) Paw of a control Kromfohrländer. (C) Hair coat of the dogs shown in panels A and B. The affected dog (left) has a more irregular coat appearance in comparison to the unaffected control dog (right). Both dogs are representatives of the wire-haired (“rough-coated”) Kromfohrländer variety.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "phenotype"], "article_id"=>1027899, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.g004", "stats"=>{"downloads"=>3, "page_views"=>245, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_phenotype_of_digital_hyperkeratosis_/1027899", "title"=>"Clinical phenotype of digital hyperkeratosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499086"], "description"=>"<p>All mammals share identical amino acid sequences in the region of the variant. The sequences were derived from the following database accessions: <i>C. lupus</i> XP_003434684.1, <i>H. sapiens</i> NP_001035088.2, <i>B. taurus</i> NP_001192445.1, <i>M. musculus</i> NP_848733.2, <i>R. norvegicus</i> XP_002727764.1.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "arginine", "residue", "52", "fam83g"], "article_id"=>1027898, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.g003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolutionary_conservation_of_the_arginine_residue_at_position_52_in_the_FAM83G_protein_/1027898", "title"=>"Evolutionary conservation of the arginine residue at position 52 in the FAM83G protein.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499089"], "description"=>"<p>Association of the <i>FAM83G:c.155G>C</i> variant with the HFH phenotype.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "variant", "hfh"], "article_id"=>1027901, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.t002", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_the_FAM83G_c_155G_gt_C_variant_with_the_HFH_phenotype_/1027901", "title"=>"Association of the <i>FAM83G:c.155G>C</i> variant with the HFH phenotype.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499088"], "description"=>"<p>(A) Haematoxylin and eosin (HE) stained paw pad section from a non-affected control dog. Note the relatively thin layer of orthokeratotic keratin on the epidermal surface. (B) Paw pad of a 1 year old affected Kromfohrländer. Note the moderate epidermal hyperplasia with papillated epidermal protrusions to the outside. The epidermis is covered by abundant compact orthokeratotic keratin. (C) Higher magnification of the same biopsy as shown in panel B. Note that the epidermis is regularly differentiated and no nuclei are seen in the stratum corneum.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "findings", "palmoplantar"], "article_id"=>1027900, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.g005", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathological_findings_in_the_palmoplantar_epidermis_/1027900", "title"=>"Histopathological findings in the palmoplantar epidermis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499085"], "description"=>"<p>A fragment harboring exon 2 and flanking sequences of the <i>FAM83G</i> gene was PCR-amplified and sequenced with the Sanger method. The figure shows representative traces from Kromfohrländer with the 3 different genotypes. The position of the variant is indicated by an arrow.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases"], "article_id"=>1027897, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.g002", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electropherograms_of_the_FAM83G_c_155G_gt_C_variant_/1027897", "title"=>"Electropherograms of the <i>FAM83G:c.155G>C</i> variant.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499084"], "description"=>"<p>(A) A genome-wide association study in Kromfohrländer using 13 cases and 29 controls indicates a strong signal with multiple associated SNPs on CFA 5. (B) The association is replicated in a cohort of 10 Irish Terrier cases and 21 controls. (C) Homozygosity mapping. Each horizontal bar corresponds to one of the 23 analyzed cases. Homozygous regions with shared alleles are shown in color. A shared homozygous interval of 611 kb delineates the exact boundaries of the critical interval from 40,521,040–41,131,739 (CanFam 3.1 assembly). (D) NCBI gene annotation of the CanFam3.1 assembly in the critical interval.</p>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "hfh", "GWAS", "haplotype"], "article_id"=>1027896, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004370.g001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_of_HFH_by_GWAS_and_haplotype_analysis_/1027896", "title"=>"Mapping of HFH by GWAS and haplotype analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 03:05:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1499095", "https://ndownloader.figshare.com/files/1499097", "https://ndownloader.figshare.com/files/1499098"], "description"=>"<div><p>Hereditary footpad hyperkeratosis (HFH) represents a palmoplantar hyperkeratosis, which is inherited as a monogenic autosomal recessive trait in several dog breeds, such as e.g. Kromfohrländer and Irish Terriers. We performed genome-wide association studies (GWAS) in both breeds. In Kromfohrländer we obtained a single strong association signal on chromosome 5 (p<sub>raw</sub> = 1.0×10<sup>−13</sup>) using 13 HFH cases and 29 controls. The association signal replicated in an independent cohort of Irish Terriers with 10 cases and 21 controls (p<sub>raw</sub> = 6.9×10<sup>−10</sup>). The analysis of shared haplotypes among the combined Kromfohrländer and Irish Terrier cases defined a critical interval of 611 kb with 13 predicted genes. We re-sequenced the genome of one affected Kromfohrländer at 23.5× coverage. The comparison of the sequence data with 46 genomes of non-affected dogs from other breeds revealed a single private non-synonymous variant in the critical interval with respect to the reference genome assembly. The variant is a missense variant (c.155G>C) in the <i>FAM83G</i> gene encoding a protein with largely unknown function. It is predicted to change an evolutionary conserved arginine into a proline residue (p.R52P). We genotyped this variant in a larger cohort of dogs and found perfect association with the HFH phenotype. We further studied the clinical and histopathological alterations in the epidermis <i>in vivo</i>. Affected dogs show a moderate to severe orthokeratotic hyperplasia of the palmoplantar epidermis. Thus, our data provide the first evidence that FAM83G has an essential role for maintaining the integrity of the palmoplantar epidermis.</p></div>", "links"=>[], "tags"=>["agriculture", "Animal management", "Animal breeding", "Animal welfare", "Computational biology", "genome analysis", "Genome-wide association studies", "molecular biology", "Molecular biology techniques", "Sequencing techniques", "Genome sequencing", "genetics", "Animal genetics", "Genetics of disease", "genomics", "Veterinary science", "Veterinary medicine", "dermatology", "Dermatologic pathology", "Hair and nail diseases", "mutation", "dogs", "hereditary", "footpad", "hyperkeratosis"], "article_id"=>1027905, "categories"=>["Biological Sciences"], "users"=>["Michaela Drögemüller", "Vidhya Jagannathan", "Doreen Becker", "Cord Drögemüller", "Claude Schelling", "Jocelyn Plassais", "Cécile Kaerle", "Caroline Dufaure de Citres", "Anne Thomas", "Eliane J. Müller", "Monika M. Welle", "Petra Roosje", "Tosso Leeb"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004370.s001", "https://dx.doi.org/10.1371/journal.pgen.1004370.s002", "https://dx.doi.org/10.1371/journal.pgen.1004370.s003"], "stats"=>{"downloads"=>1, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Mutation_in_the_FAM83G_Gene_in_Dogs_with_Hereditary_Footpad_Hyperkeratosis_HFH_/1027905", "title"=>"A Mutation in the <i>FAM83G</i> Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-15 03:05:50"}

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