Chicks and single-nucleotide polymorphisms: an entrée into identifying genes conferring disease resistance in chicken
Hans H. Cheng A B E , Sean MacEachern C , Sugalesini Subramaniam B and William M. Muir DA USDA, ARS, Avian Disease and Oncology Laboratory, 3606 East Mount Hope Road, East Lansing, MI 48823, USA.
B Comparative Medicine and Integrative Biology Graduate Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
C Cobb-Vantress Inc., PO Box 1030, 4703 US Highway 412 East, Siloam Springs, AR 72761, USA.
D Department of Animal Sciences, 1151 Lilly Hall, Purdue University, West Lafayette, IN 47907, USA.
E Corresponding author. Email: hans.cheng@ars.usda.gov
Animal Production Science 52(3) 151-156 https://doi.org/10.1071/AN11099
Submitted: 3 June 2011 Accepted: 12 January 2012 Published: 13 February 2012
Journal Compilation © CSIRO Publishing 2012 Open Access CC BY-NC-ND
Abstract
Marek’s disease (MD) is one of the most serious chronic infectious disease threats to the poultry industry worldwide. Selecting for increased genetic resistance to MD is a control strategy that can augment current vaccinal control measures. Although our previous efforts integrating various genomic screens successfully identified three resistance genes, the main limitation was mapping precision, which hindered our ability to identify and further evaluate high-confidence candidate genes. Towards identifying the remaining genes of this complex trait, we incorporated three additional approaches made substantially more powerful through next-generation sequencing and that exploit the growing importance of expression variation. First, we screened for allele-specific expression (ASE) in response to Marek’s disease virus (MDV) infection, which, when allelic imbalance was identified, is sufficient to indicate a cis-acting element for a specific gene. Second, sequencing of genomic regions enriched by chromatin immunoprecipitation (ChIP) combined with transcript profiling identified motifs bound and genes directly regulated by MDV Meq, a bZIP transcription factor and the viral oncogene. Finally, analysis of genomic sequences from two experimental lines divergently selected for MD genetic resistance allowed inference about regions under selection as well as potential causative polymorphisms. These new combined approaches have resulted in a large number of high-confidence genes conferring MD resistance reflecting the multigenic basis of this trait, which expands our biological knowledge and provides corresponding single-nucleotide polymorhpisms (SNPs) that can be directly evaluated for their genetic contribution towards disease resistance.
Additional keywords: gene expression, genetic resistance, Marek’s disease, next-generation sequencing, poultry.
References
Brem RB, Yvert G, Clinton R, Kruglyak L (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752–755.| Genetic dissection of transcriptional regulation in budding yeast.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XjtlOnt70%3D&md5=958f465b27c51d3e9dc62bb6910177d9CAS |
Cheng H, Niikura M, Kim T, Mao W, MacLea KS, Hunt H, Dodgson J, Burnside J, Morgan R, Ouyang M, Lamont S, Dekkers J, Fulton J, Soller M, Muir W (2008) Using integrative genomics to elucidate genetic resistance to Marek’s disease in chickens. In ‘Animal genomics for animal health. Developments in biologicals. Vol. 132’. (Eds M-H Pinard, C Gay, P-P Pastoret, B Dodet) pp. 365–372. (Karger: Basel, Switzerland)
Hillier LW, Miller W, Birney E, Warren W, Hardison RC, et al International Chicken Genome Sequencing Consortium (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432, 695–716.
| Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVGmtb7M&md5=cf7c36ddc1f0793a557c6bbd830d1cf0CAS |
Himly M, Foster DN, Bottoli I, Iacovoni JS, Vogt PK (1998) The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses. Virology 248, 295–304.
| The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXlvVOntrk%3D&md5=6f445d92bfdacffa4216a0e8e19f4f8bCAS |
Jones D, Lucy L, Liu JL, Kung HJ, Tillotson JK (1992) Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymnphoblastoid tumors. Proceedings of the National Academy of Sciences, USA 89, 4042–4046.
| Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymnphoblastoid tumors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXitV2jtLs%3D&md5=d3857f33077f79d8d86b898de1edcb37CAS |
Keane TM, Goodstadt L, Danecek P, White MA, Wong K, et al (2011) Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477, 289–294.
| Mouse genomic variation and its effect on phenotypes and gene regulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFOlsL7N&md5=f71d7e1275c07df5b3a0c4f783be1962CAS |
King MC, Wilson AC (1975) Evolution at two levels in human and chimpanzees. Science 188, 107–116.
| Evolution at two levels in human and chimpanzees.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2MXhs1Orur4%3D&md5=ec42178cc2413498b233dcf7eb81cfa8CAS |
Knight JC (2005) Regulatory polymorphisms underlying complex disease traits. Journal of Molecular Medicine 83, 97–109.
Kreager K (1996) Industry concerns workshop. In ‘Current research on Marek’s disease’. (Eds RF Silva, HH Cheng, PM Coussens, LF Lee, LF Velicer) pp. 509–511. (American Association of Avian Pathologists: Kennett Square, PA)
Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biology 10, R25
| Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.Crossref | GoogleScholarGoogle Scholar |
Levy AM, Izumiya Y, Brunovskis P, Xia L, Parcells MS, Reddy SM, Lee L, Chen HW, Kung HJ (2003) Characterization of the chromosomal binding sites and dimerization partners of the viral oncoprotein Meq in Marek’s disease virus-transformed T cells. Journal of Virology 77, 12 841–12 851.
| Characterization of the chromosomal binding sites and dimerization partners of the viral oncoprotein Meq in Marek’s disease virus-transformed T cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptFOjsLc%3D&md5=dc577a2299b350b72023b6b216bbe00dCAS |
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R (2009) The sequence alignment/map format (SAM) and SAMtools. Bioinformatics 25, 2078–2079.
| The sequence alignment/map format (SAM) and SAMtools.Crossref | GoogleScholarGoogle Scholar |
Liu HC, Kung HJ, Fulton JE, Morgan RW, Cheng HH (2001) Growth hormone interacts with the Marek’s disease virus SORF2 protein and is associated with disease resistance in chicken. Proceedings of the National Academy of Sciences, USA 98, 9203–9208.
| Growth hormone interacts with the Marek’s disease virus SORF2 protein and is associated with disease resistance in chicken.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlvFSrsrs%3D&md5=37680cbe7a8aa4f2c48b7506a13a5199CAS |
Lupiani B, Lee LF, Cui X, Gimeno I, Anderson A, Morgan RW, Silva RF, Witter RL, Reddy SM (2004) Marek’s disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication. Proceedings of the National Academy of Sciences, USA 101, 11 815–11 820.
| Marek’s disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXntVers7o%3D&md5=73582d7f823cc86912e14e8bfa7edba5CAS |
MacEachern S, Muir WM, Crosby S, Cheng HH (2011) Genome-wide identification of allele-specific expression (ASE) in response to Marek’s disease virus infection using next generation sequencing. BMC Proceedings 5, S14
| Genome-wide identification of allele-specific expression (ASE) in response to Marek’s disease virus infection using next generation sequencing.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnsFamtLk%3D&md5=44af39be45a83a6c02733b1b1aeaab41CAS |
Maher B (2008) The case of the missing heritability. Nature 456, 18–21.
| The case of the missing heritability.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlCjtrnM&md5=9c6f92e3d640f5fa9af932623fdbecc1CAS |
Mao W, Hunt HD, Cheng HH (2010) Cloning and functional characterization of chicken stem cell antigen 2. Developmental and Comparative Immunology 34, 360–368.
| Cloning and functional characterization of chicken stem cell antigen 2.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjvVWntA%3D%3D&md5=715e5b2c4f529ecd62b59fbcc1dcf853CAS |
Maynard Smith J, Haigh J (1974) The hitch-hiking effect of a favourable gene. Genetical Research 23, 23–35.
| The hitch-hiking effect of a favourable gene.Crossref | GoogleScholarGoogle Scholar |
Muir WM, Wong GK, Zhang Y, Wang J, Groenen MAM, Crooijmans RPMA, Megens H-J, Zhang H, Okimoto R, Vereijken A, Jungerius A, Albers GAA, Taylor Lawley C, Delany ME, MacEachern S, Cheng HH (2008) Genome-wide assessment of world-wide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds. Proceedings of the National Academy of Sciences, USA 105, 17 312–17 317.
| Genome-wide assessment of world-wide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVWlurjJ&md5=f98a605cfa310788d9a045eb95fd2443CAS |
Niikura M, Kim T, Hunt HD, Burnside J, Morgan RW, Dodgson JB, Cheng HH (2007) Marek’s disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells. Virology 359, 212–219.
| Marek’s disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhs1Snsr4%3D&md5=b15aca797b51b83f31a2b643c199e4ddCAS |
O’Neill MJ, Ingram RS, Vrana PB, Tilghman SM (2000) Allelic expression of IGF2 in marsupials and birds. Development Genes and Evolution 210, 18–20.
| Allelic expression of IGF2 in marsupials and birds.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXntlalsL4%3D&md5=640dded73993d100faa0e582580b3974CAS |
Okazaki W, Purchase HG, Burmester BR (1970) Protection against Marek’s disease by vaccination with a herpesvirus of turkeys. Avian Diseases 14, 413–429.
| Protection against Marek’s disease by vaccination with a herpesvirus of turkeys.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE3c3jtVSktA%3D%3D&md5=d36f7179052b74c7edf738e8f63f51afCAS |
Pastinen T (2010) Genome-wide allele-specific analysis: insights into regulatory variation. Nature Reviews. Genetics 11, 533–538.
| Genome-wide allele-specific analysis: insights into regulatory variation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXovFOhtr8%3D&md5=a69a1e1644d806df8954f38bd6693a96CAS |
Pickrell JK, Marioni JC, Pai AA, Degner JF, Engelhardt BE, Nkadori E, Veyrieras J-B, Stephens M, Gilad Y, Pritchard JK (2010) Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature 464, 768–772.
| Understanding mechanisms underlying human gene expression variation with RNA sequencing.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXivFKns7Y%3D&md5=6f8c3beff48eb29b334480a1df1c1256CAS |
Purchase HG (1985) Clinical disease and its economic impact. In ‘Marek’s disease, scientific basis and methods of control’. (Ed LN Payne) pp. 17–42. (Martinus Nkjhoff Publishing: Boston, MA)
Serre D, Gurd S, Ge B, Sladek R, Sinnett D, Harmsen E, Bibikova M, Chudin E, Barker DL, Dickinson T, Fan JB, Hudson TJ (2008) Differential allelic expression in the human genome: a robust approach to identify genetic and epigenetic cis-acting mechanisms regulating gene expression. PLOS Genetics 4, e1000006
| Differential allelic expression in the human genome: a robust approach to identify genetic and epigenetic cis-acting mechanisms regulating gene expression.Crossref | GoogleScholarGoogle Scholar |
Stamatoyannopoulos JA (2004) The genomics of gene expression. Genomics 84, 449–457.
| The genomics of gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmtlOksbk%3D&md5=61794b09b9d4ce73b99cfea214b9a1b5CAS |
Valouev A, Johnson DS, Sundquist A, Medina C, Anton E, Batzoglou S, Myers RM, Sidow A (2008) Genome-wide analysis of transcription factor binding sites based on ChIP-seq data. Nature Methods 5, 829–834.
| Genome-wide analysis of transcription factor binding sites based on ChIP-seq data.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVGgsb3F&md5=f30758dc8be9c84ea3faacb39dd3bf57CAS |
Witter RL (1997) Increased virulence of Marek’s disease virus field isolates. Avian Diseases 41, 149–163.
| Increased virulence of Marek’s disease virus field isolates.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2s3kt1ehuw%3D%3D&md5=0752a7011008def9c31d0aad00b9a4c2CAS |
Witter RL (2001) Protective efficacy of Marek’s disease vaccine. In ‘Marek’s disease’. (Ed. K Hirai) pp. 57–90. (Springer-Verlag: New York)
Witter RL, Nazerian K, Purchase HG, Burgoyne GH (1970) Isolation from turkeys of a cell-associated herpesvirus antigenically related to Marek’s disease virus. American Journal of Veterinary Research 31, 525–538.
Wray GA (2007) The evolutionary significance of cis-regulatory mutations. Nature Reviews. Genetics 8, 206–216.
| The evolutionary significance of cis-regulatory mutations.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhslOgt7w%3D&md5=c9ad56e38c77649a7d63c50e95666d06CAS |
Yan H, Yuan W, Velculescu VE, Vogelstein B, Kinzler KW (2002) Allelic variation in human gene expression. Science 297, 1143
| Allelic variation in human gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XmsVOiu7s%3D&md5=b72f83d12b64d6932111c3981743004cCAS |
Yokomine T, Hata K, Tsudzuki M, Sasaki H (2006) Evolution of the vertebrate DNMT3 gene family: a possible link between existence of DNMT3L and genomic imprinting. Cytogenetic and Genome Research 113, 75–80.
| Evolution of the vertebrate DNMT3 gene family: a possible link between existence of DNMT3L and genomic imprinting.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtVSqtL4%3D&md5=fe7677efb2ba7f56bf7559c2e4e35e28CAS |