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A deletion in the Hermansky–Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish

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Abstract

Albinism is caused by a series of genetic abnormalities leading to reduction of melanin production. Albinism is quite frequent in catfish, but the causative gene and the molecular basis were unknown. In this study, we conducted a genome-wide association study (GWAS) using the 250 K SNP array. The GWAS analysis allowed mapping of the albino phenotype in the Hermansky–Pudlak syndrome 4 (Hps4) gene, which is known to be involved in melanosome biosynthesis. Sequencing analysis revealed that a 99-bp deletion was present in all analyzed albino catfish at the intron 2 and exon 3 junction. This deletion led to the skipping of the entire exon 3 which was confirmed by RT-PCR. Therefore, Hps4 was determined to be the candidate gene of the catfish albinism.

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Abbreviations

HPS:

Hermansky–Pudlak syndrome

UV:

Ultraviolet

OCA:

Oculocutaneous albinism

GWAS:

Genome-wide association study

QTL:

Quantitative trait loci

SNP:

Single nucleotide polymorphism

PCA:

Principal component analysis

GEF:

Guanine nucleotide exchange factor

BLOC3S2:

Biogenesis of lysosome-related organelles complexes 3, subunit 2

References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  • Bachli EB, Brack T, Eppler E, Stallmach T, Trueb RM, Huizing M, Gahl WA (2004) Hermansky–Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis. Am J Med Genet A 127A:201–207

    Article  PubMed  Google Scholar 

  • Bassi MT, Schiaffino MV, Renieri A, De Nigris F, Galli L, Bruttini M, Gebbia M, Bergen AA, Lewis RA, Ballabio A (1995) Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet 10:13–19

    Article  CAS  PubMed  Google Scholar 

  • Beirl AJ, Linbo TH, Cobb MJ, Cooper CD (2014) oca2 Regulation of chromatophore differentiation and number is cell type specific in zebrafish. Pigment Cell. Melanoma Res 27:178–189

    Article  CAS  Google Scholar 

  • Boissy RE, Zhao H, Oetting WS, Austin LM, Wildenberg SC, Boissy YL, Zhao Y, Sturm RA, Hearing VJ, King RA, Nordlund JJ (1996) Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as “OCA3”. Am J Hum Genet 58:1145–1156

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brenner M, Hearing VJ (2008) The protective role of melanin against UV damage in human skin. Photochem Photobiol 84:539–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dooley CM, Schwarz H, Mueller KP, Mongera A, Konantz M, Neuhauss SC, Nusslein-Volhard C, Geisler R (2013) Slc45a2 and V-ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease. Pigment Cell. Melanoma Res 26:205–217

    Article  CAS  Google Scholar 

  • Geng X, Liu S, Yao J, Bao L, Zhang J, Li C, Wang R, Sha J, Zeng P, Zhi D, Liu Z (2016) A Genome-Wide Association Study Identifies Multiple Regions Associated with Head Size in Catfish. G3 6(10):3389–3398

    PubMed  PubMed Central  Google Scholar 

  • Geng X, Sha J, Liu S, Bao L, Zhang J, Wang R, Yao J, Li C, Feng J, Sun F, Sun L, Jiang C, Zhang Y, Chen A, Dunham R, Zhi D, Liu Z (2015) A genome-wide association study in catfish reveals the presence of functional hubs of related genes within QTLs for columnaris disease resistance. BMC Genom 16:196

    Article  Google Scholar 

  • Gerondopoulos A, Langemeyer L, Liang JR, Linford A, Barr FA (2012) BLOC-3 mutated in Hermansky–Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Curr Biol 22:2135–2139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gronskov K, Dooley CM, Ostergaard E, Kelsh RN, Hansen L, Levesque MP, Vilhelmsen K, Mollgard K, Stemple DL, Rosenberg T (2013) Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. Am J Hum Genet 92:415–421

    Article  PubMed  PubMed Central  Google Scholar 

  • Gross JB, Borowsky R, Tabin CJ (2009) A novel role for Mc1r in the parallel evolution of depigmentation in independent populations of the cavefish Astyanax mexicanus. PLoS Genet 5:e1000326

    Article  PubMed  PubMed Central  Google Scholar 

  • Jin Y, Zhou T, Geng X, Liu S, Chen A, Yao J, Jiang C, Tan S, Su B, Liu Z (2016) A genome-wide association study of heat stress-associated SNPs in catfish. Anim Genet 48(2):233–236

    Article  PubMed  Google Scholar 

  • Kamaraj B, Purohit R (2014) Mutational analysis of oculocutaneous albinism: a compact review. Biomed Res Int 2014:905472

    PubMed  PubMed Central  Google Scholar 

  • Kang HM, Sul JH, Service SK, Zaitlen NA, Kong SY, Freimer NB, Sabatti C, Eskin E (2010) Variance component model to account for sample structure in genome-wide association studies. Nat Genet 42:348–354

  • Kausar T, Bhatti MA, Ali M, Shaikh RS, Ahmed ZM (2013) OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q24. Clin Genet 84:91–93

    Article  CAS  PubMed  Google Scholar 

  • Kelsh RN, Brand M, Jiang YJ, Heisenberg CP, Lin S, Haffter P, Odenthal J, Mullins MC, van Eeden FJ, Furutani-Seiki M, Granato M, Hammerschmidt M, Kane DA, Warga RM, Beuchle D, Vogelsang L, Nusslein-Volhard C (1996) Zebrafish pigmentation mutations and the processes of neural crest development. Development 123:369–389

    CAS  PubMed  Google Scholar 

  • Krauss J, Geiger-Rudolph S, Koch I, Nusslein-Volhard C, Irion U (2014) A dominant mutation in tyrp1A leads to melanophore death in zebrafish. Pigment Cell. Melanoma Res 27:827–830

    Article  CAS  Google Scholar 

  • Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O’Donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310:1782–1786

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Liu S, Yao J, Bao L, Zhang J, Li Y, Jiang C, Sun L, Wang R, Zhang Y, Zhou T, Zeng Q, Fu Q, Gao S, Li N, Koren S, Jiang Y, Zimin A, Xu P, Phillippy AM, Geng X, Song L, Sun F, Li C, Wang X, Chen A, Jin Y, Yuan Z, Yang Y, Tan S, Peatman E, Lu J, Qin Z, Dunham R, Li Z, Sonstegard T, Feng J, Danzmann RG, Schroeder S, Scheffler B, Duke MV, Ballard L, Kucuktas H, Kaltenboeck L, Liu H, Armbruster J, Xie Y, Kirby ML, Tian Y, Flanagan ME, Mu W, Waldbieser GC (2016) The channel catfish genome sequence provides insights into the evolution of scale formation in teleosts. Nat Commun 7:11757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Sun L, Li Y, Sun F, Jiang Y, Zhang Y, Zhang J, Feng J, Kaltenboeck L, Kucuktas H, Liu Z (2014) Development of the catfish 250 K SNP array for genome-wide association studies. BMC Res Notes 7:135

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu S, Zhou Z, Lu J, Sun F, Wang S, Liu H, Jiang Y, Kucuktas H, Kaltenboeck L, Peatman E, Liu Z (2011) Generation of genome-scale gene-associated SNPs in catfish for the construction of a high-density SNP array. BMC Genom 12:53

    Article  CAS  Google Scholar 

  • Lund PM (2005) Oculocutaneous albinism in southern Africa: population structure, health and genetic care. Ann Hum Biol 32:168–173

    Article  CAS  PubMed  Google Scholar 

  • Lund PM, Taylor JS (2008) Lack of adequate sun protection for children with oculocutaneous albinism in South Africa. BMC Public Health 8:225

    Article  PubMed  PubMed Central  Google Scholar 

  • Meredith P, Sarna T (2006) The physical and chemical properties of eumelanin. Pigment Cell Res 19:572–594

    Article  CAS  PubMed  Google Scholar 

  • Nakamura K, Ozaki A, Akutsu T, Iwai K, Sakamoto T, Yoshizaki G, Okamoto N (2001) Genetic mapping of the dominant albino locus in rainbow trout (Oncorhynchus mykiss). Mol Genet Genom 265:687–693

    Article  CAS  Google Scholar 

  • Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, Brilliant MH (2001) Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4. Am J Hum Genet 69:981–988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen T, Novak EK, Kermani M, Fluhr J, Peters LL, Swank RT, Wei ML (2002) Melanosome morphologies in murine models of Hermansky–Pudlak syndrome reflect blocks in organelle development. J Invest Dermatol 119:1156–1164

    Article  CAS  PubMed  Google Scholar 

  • Nordmann M, Cabrera M, Perz A, Brocker C, Ostrowicz C, Engelbrecht-Vandre S, Ungermann C (2010) The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7. Curr Biol 20:1654–1659

    Article  CAS  PubMed  Google Scholar 

  • Protas ME, Hersey C, Kochanek D, Zhou Y, Wilkens H, Jeffery WR, Zon LI, Borowsky R, Tabin CJ (2006) Genetic analysis of cavefish reveals molecular convergence in the evolution of albinism. Nat Genet 38:107–111

    Article  CAS  PubMed  Google Scholar 

  • Pruitt KD, Tatusova T, Maglott DR (2007) NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 35:D61–D65

    Article  CAS  PubMed  Google Scholar 

  • Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raposo G, Marks MS (2007) Melanosomes–dark organelles enlighten endosomal membrane transport. Nat Rev Mol Cell Biol 8:786–797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rinchik EM, Bultman SJ, Horsthemke B, Lee ST, Strunk KM, Spritz RA, Avidano KM, Jong MT, Nicholls RD (1993) A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature 361:72–76

    Article  CAS  PubMed  Google Scholar 

  • Salamov AA, Solovyev VV (2000) Ab initio gene finding in Drosophila genomic DNA. Genome Res 10:516–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheinfeld NS (2003) Syndromic albinism: a review of genetics and phenotypes. Dermatol Online J 9:5

    PubMed  Google Scholar 

  • Seward SL Jr, Gahl WA (2013) Hermansky–Pudlak syndrome: health care throughout life. Pediatrics 132:153–160

    Article  PubMed  Google Scholar 

  • Slavik O, Horky P, Maciak M (2015) Ostracism of an albino individual by a group of pigmented catfish. PLoS One 10:e0128279

    Article  PubMed  PubMed Central  Google Scholar 

  • Slavik O, Horky P, Wackermannova M (2016) How does agonistic behaviour differ in albino and pigmented fish? PeerJ 4:e1937

    Article  PubMed  PubMed Central  Google Scholar 

  • Tomita Y, Takeda A, Okinaga S, Tagami H, Shibahara S (1989) Human oculocutaneous albinism caused by single base insertion in the tyrosinase gene. Biochem Biophys Res Commun 164:990–996

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Liu S, Jiang C, Geng X, Zhou T, Li N, Bao L, Li Y, Yao J, Yang Y, Zhong X, Jin Y, Dunham R, Liu Z (2017) Multiple across-strain and within-strain QTLs suggest highly complex genetic architecture for hypoxia tolerance in channel catfish. Mol Genet Genom 292:63–76

    Article  CAS  Google Scholar 

  • Wasmeier C, Hume AN, Bolasco G, Seabra MC (2008) Melanosomes at a glance. J Cell Sci 121:3995–3999

    Article  CAS  PubMed  Google Scholar 

  • Wei AH, Zang DJ, Zhang Z, Liu XZ, He X, Yang L, Wang Y, Zhou ZY, Zhang MR, Dai LL, Yang XM, Li W (2013) Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. J Invest Dermatol 133:1834–1840

    Article  CAS  PubMed  Google Scholar 

  • Yang T, Li X, Huang Q, Li L, Chai Y, Sun L, Wang X, Zhu Y, Wang Z, Huang Z, Li Y, Wu H (2013) Double heterozygous mutations of MITF and PAX3 result in Waardenburg syndrome with increased penetrance in pigmentary defects. Clin Genet 83:78–82

    Article  CAS  PubMed  Google Scholar 

  • Zhou T, Liu S, Geng X, Jin Y, Jiang C, Bao L, Yao J, Zhang Y, Zhang J, Sun L, Wang X, Li N, Tan S, Liu Z (2017) GWAS analysis of QTL for enteric septicemia of catfish and their involved genes suggest evolutionary conservation of a molecular mechanism of disease resistance. Mol Genet Genom 292:231–242

    Article  CAS  Google Scholar 

  • Zou M, Zhang X, Shi Z, Lin L, Ouyang G, Zhang G, Zheng H, Wei K, Ji W (2015) A Comparative Transcriptome Analysis between Wild and Albino Yellow Catfish (Pelteobagrus fulvidraco). PLoS One 10(6):e0131504

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This project was partially supported by a competitive AFRI Grant from the Animal Genomics, Genetics and Breeding Program of the USDA National Institute of Food and Agriculture (Grant Number 2015-67015-22907), and partially by a competitive AFRI Grant from the Animal Health Program (Grant Number 2015-67015-22975) of the USDA National Institute of Food and Agriculture (NIFA). We thank Lyudmila Kaltenboeck, Huseyin Kucuktas, Zihao Yuan, and Changxu Tian for technical assistance. We would also like to thank Jiaren Zhang and Fanyue Sun for sample collection.

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    Authors and Affiliations

    1. Aquatic Genomics Unit, Fish Molecular Genetics and Biotechnology Laboratory, School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, 36849, USA

      Yueru Li, Xin Geng, Lisui Bao, Ahmed Elaswad, Rex Dunham & Zhanjiang Liu

    2. Division: Department of Nutrition, Dietetics and Hospitality Management, Auburn University, Auburn, AL, 36849, USA

      Yueru Li & Kevin W. Huggins

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    1. Yueru Li
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    2. Xin Geng
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    3. Lisui Bao
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    Correspondence to Zhanjiang Liu.

    Ethics declarations

    The authors declare no conflict of interest. All experiments involving the handling and treatment of fish were approved by the Institutional Animal Care and Use Committee (IACUC) at Auburn University. Tissue samples were collected after euthanasia. All animal procedures were carried out according to the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act in the United States.

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    Communicated by S. Hohmann.

    Y. Li and X. Geng authors contributed equally to this work.

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    Supplementary material 1 (DOCX 27 KB)

    438_2017_1302_MOESM2_ESM.tif

    Fig. S1 Sample structure identified by principal component analysis with the first two principal component scores. The coordinates are the first two principal component scores. (TIF 446 KB)

    438_2017_1302_MOESM3_ESM.tif

    Fig. S2 Sequence analyses revealed the skipping of exon 3 in the Hps4 gene of albino catfish. Characters in orange color is the mRNA sequence of exon 3. (TIF 93 KB)

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    Li, Y., Geng, X., Bao, L. et al. A deletion in the Hermansky–Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish. Mol Genet Genomics 292, 663–670 (2017). https://doi.org/10.1007/s00438-017-1302-8

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    • DOI: https://doi.org/10.1007/s00438-017-1302-8

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