A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)

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The palms and soles of mammals are covered by the palmoplantar epidermis, which has to bear immense mechanical forces and has therefore a special composition in comparison to the epidermis on regular skin. We studied a Mendelian disease in dogs, termed hereditary footpad hyperkeratosis (HFH). HFH affected dogs develop deep fissures in the paw pads, which are the consequence of a pathological thickening of the outermost layer of the epidermis. We mapped the disease causing genetic variant in the Kromfohrländer and Irish Terrier breeds to a 611 kb interval on chromosome 5. HFH affected Kromfohrländer and Irish Terriers shared the same haplotype indicating descent from a common founder. We re-sequenced the genome of an affected dog and compared it to genome sequences of 46 control dogs. The HFH affected dog had only one private non-synonymous variant in the critical interval, a missense variant of the FAM83G gene. We genotyped this variant in more than 500 dogs and found perfect association with the HFH phenotype. Our data very strongly suggest that the FAM83G variant is causative for HFH. FAM83G is a protein with unknown biochemical function. Our study thus provides the first link between this protein and the palmoplantar epidermis.

Vyšlo v časopise: A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH). PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004370
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004370

Souhrn

Zdroje

1. ReisA, HenniesHC, LangbeinL, DigweedM, MischkeD, et al. (1994) Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK). Nat Genet 6: 174–179.

2. FuDJ, ThomsonC, LunnyDP, Dopping-HepenstalPJ, McGrathJA, et al. (2013) Keratin 9 is required for the structural integrity and terminal differentiation of the palmoplantar epidermis. J Invest Dermatol 134: 754–63 doi: 10.1038/jid.2013.356

3. KimonisV, DiGiovannaJJ, YangJM, DoyleSZ, BaleSJ, et al. (1994) A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma. J Invest Dermatol 103: 764–769.

4. MoraisP, MotaA, BaudrierT, LopesJM, CerqueiraR, et al. (2009) Epidermolytic hyperkeratosis with palmoplantar keratoderma in a patient with KRT10 mutation. Eur J Dermatol 19: 333–336.

5. McLeanWH, RuggEL, LunnyDP, MorleySM, LaneEB, et al. (1995) Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 9: 273–278.

6. ShamsherMK, NavsariaHA, StevensHP, RatnavelRC, PurkisPE, et al. (1995) Novel mutations in keratin 16 gene underly focal non-epidermolytic palmoplantar keratoderma (NEPPK) in two families. Hum Mol Genet 4: 1875–1881.

7. LessardJC, CoulombePA (2012) Keratin 16-null mice develop palmoplantar keratoderma, a hallmark feature of pachyonychia congenita and related disorders. J Invest Dermatol 132: 1384–1391.

8. BlaydonDC, LindLK, PlagnolV, LintonKJ, SmithFJ, et al. (2013) Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma. Am J Hum Genet 93: 330–335.

9. McLeanWH, IrvineAD (2007) Disorders of keratinisation: from rare to common genetic diseases of skin and other epithelial tissues. Ulster Med J 76: 72–82.

10. McLeanWH, MooreCB (2011) Keratin disorders: from gene to therapy. Hum Mol Genet 20: R189–R197.

11. KarlssonEK, Lindblad-TohK (2008) Leader of the pack: gene mapping in dogs and other model organisms. Nat Rev Genet 9: 713–725.

12. CadieuE, NeffMW, QuignonP, WalshK, ChaseK, et al. (2009) Coat variation in the domestic dog is governed by variants in three genes. Science 326: 150–153.

13. DrögemüllerC, KarlssonEK, HytönenMK, PerloskiM, DolfG, et al. (2008) A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321: 1462.

14. GrallA, GuaguèreE, PlanchaisS, GrondS, BourratE, et al. (2012) PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet 44: 140–147.

15. FormanOP, PenderisJ, HartleyC, HaywardLJ, RickettsSL, et al. (2012) Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed. PLoS Genet 8: e1002462.

16. OlssonM, MeadowsJR, TruvéK, Rosengren PielbergG, PuppoF, et al. (2011) A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs. PLoS Genet 7: e1001332.

17. JagannathanV, BannoehrJ, PlattetP, HauswirthR, DrögemüllerC, et al. (2013) A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation. PLoS Genet 9: e1003848.

18. BinderH, ArnoldS, SchellingC, SuterM, WildP (2000) Palmoplantar hyperkeratosis in Irish terriers: evidence of autosomal recessive inheritance. J Small Anim Pract 41: 52–55.

19. SchleiferSG, VersteegSA, van OostB, WillemseT (2003) Familial footpad hyperkeratosis and inheritance of keratin 2, keratin 9, and desmoglein 1 in two pedigrees of Irish Terriers. Am J Vet Res 64: 715–720.

20. KumarP, HenikoffS, NgPC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4: 1073–1081.

21. AdzhubeiIA, SchmidtS, PeshkinL, RamenskyVE, GerasimovaA, et al. (2010) A method and server for predicting damaging missense mutations. Nat Methods 7: 248–249.

22. Ferrer-CostaC, GelpíJL, ZamakolaL, ParragaI, de la CruzX, et al. (2005) PMUT: a web-based tool for the annotation of pathological mutations on proteins. Bioinformatics 21: 3176–3178.

23. RaddenLA2nd, ChildKM, AdkinsEB, SpacekDV, FelicianoAM, et al. (2013) The wooly mutation (wly) on mouse chromosome 11 is associated with a genetic defect in Fam83g. BMC Res Notes 6: 189.

24. Harris B, Ward-Bailey PF, Bronson RT (2003) Wooly: a new hair mutation on mouse chromosome 11. Mouse mutant resources Web site. Bar Harbor, Maine: The Jackson Laboratory, MGI Direct Data Submission. Available http://mousemutant.jax.org/articles/MMRmutantwooly.html. Accessed 29 November 2013.

25. KimJW, LeeSK, LeeZH, ParkJC, LeeKE, et al. (2008) FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet 82: 489–494.

26. PurcellS, NealeB, Todd-BrownK, ThomasL, FerreiraMA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559–575.

27. AulchenkoYS, RipkeS, IsaacsA, van DuijnC (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23: 1294–1296.

28. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.

29. McKennaA, HannaM, BanksE, SivachenkoA, CibulskisK, et al. (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297–1303.

30. CingolaniP, PlattsA, CoonM, NguyenT, WangL, et al. (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 6: 80–92.

31. ZeitouniB, BoevaV, Janoueix-LeroseyI, LoeilletS, Legoix-néP, et al. (2010) SVDetect: a tool to identify genomic structural variations from paired-end and mate-pair sequencing data. Bioinformatics 26: 1895–1896.

32. ChervetL, GalichetA, McLeanWH, ChenH, SuterMM, et al. (2010) Missing C-terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis. Exp Dermatol 19: e343–346.