Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Fertility and genomics: comparison of gene expression in contrasting reproductive tissues of female cattle

P. A. McGettigan A , J. A. Browne A , S. D. Carrington B , M. A. Crowe B , T. Fair A , N. Forde A F , B. J. Loftus C D , A. Lohan C , P. Lonergan A , K. Pluta B , S. Mamo A , A. Murphy D , J. Roche C , S. W. Walsh A G , C. J. Creevey E H , B. Earley E , S. Keady E , D. A. Kenny E , D. Matthews E , M. McCabe E , D. Morris E , A. O’Loughlin E , S. Waters E , M. G. Diskin E and A. C. O. Evans A D I
+ Author Affiliations
- Author Affiliations

A School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.

B School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

C School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland.

D Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

E Animal and Grassland Research and Innovation Centre, Teagasc, Athenry, County Galway, Ireland.

F Present Address: Division of Reproduction and Early Development, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK.

G Present Address: Department of Chemical and Life Sciences, Waterford Institute of Technology, Waterford, Ireland.

H Present Address: Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Ceredigion SY23 3DA, UK.

I Corresponding author. Email: alex.evans@ucd.ie

Reproduction, Fertility and Development 28(2) 11-24 https://doi.org/10.1071/RD15354
Published: 3 December 2015

Abstract

To compare gene expression among bovine tissues, large bovine RNA-seq datasets were used, comprising 280 samples from 10 different bovine tissues (uterine endometrium, granulosa cells, theca cells, cervix, embryos, leucocytes, liver, hypothalamus, pituitary, muscle) and generating 260 Gbases of data. Twin approaches were used: an information–theoretic analysis of the existing annotated transcriptome to identify the most tissue-specific genes and a de-novo transcriptome annotation to evaluate general features of the transcription landscape. Expression was detected for 97% of the Ensembl transcriptome with at least one read in one sample and between 28% and 66% at a level of 10 tags per million (TPM) or greater in individual tissues. Over 95% of genes exhibited some level of tissue-specific gene expression. This was mostly due to different levels of expression in different tissues rather than exclusive expression in a single tissue. Less than 1% of annotated genes exhibited a highly restricted tissue-specific expression profile and approximately 2% exhibited classic housekeeping profiles. In conclusion, it is the combined effects of the variable expression of large numbers of genes (73%–93% of the genome) and the specific expression of a small number of genes (<1% of the transcriptome) that contribute to determining the outcome of the function of individual tissues.

Additional keywords: cervix, embryo, endometrium, follicle, reproduction, RNA-seq, transcription, uterus.


References

Anders, S., and Huber, W. (2010). Differential expression analysis for sequence count data. Genome Biol. 11, R106.
Differential expression analysis for sequence count data.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVahs7bI&md5=3fa7b0b2367925135fd7443898013fcdCAS | 20979621PubMed |

Anders, S., Reyes, A., and Huber, W. (2012). Detecting differential usage of exons from RNA-seq data. Genome Res. 22, 2008–2017.
Detecting differential usage of exons from RNA-seq data.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsVKhsrjN&md5=4652aefac3788d144f10603af0fd7685CAS | 22722343PubMed |

Bainbridge, M. N., Warren, R. L., Hirst, M., Romanuik, T., Zeng, T., Go, A., Delaney, A., Griffith, M., Hickenbotham, M., Magrini, V., Mardis, E. R., Sadar, M. D., Siddiqui, A. S., Marra, M. A., and Jones, S. J. (2006). Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics 7, 246.
Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach.Crossref | GoogleScholarGoogle Scholar | 17010196PubMed |

Birney, E., Stamatoyannopoulos, J. A., Dutta, A., Guigo, R., Gingeras, T. R., Margulies, E. H., Weng, Z., Snyder, M., Dermitzakis, E. T., Thurman, R. E., Kuehn, M. S., Taylor, C. M., Neph, S., Koch, C. M., Asthana, S., Malhotra, A., Adzhubei, I., Greenbaum, J. A., Andrews, R. M., Flicek, P., Boyle, P. J., Cao, H., Carter, N. P., Clelland, G. K., Davis, S., Day, N., Dhami, P., Dillon, S. C., Dorschner, M. O., Fiegler, H., Giresi, P. G., Goldy, J., Hawrylycz, M., Haydock, A., Humbert, R., James, K. D., Johnson, B. E., Johnson, E. M., Frum, T. T., Rosenzweig, E. R., Karnani, N., Lee, K., Lefebvre, G. C., Navas, P. A., Neri, F., Parker, S. C., Sabo, P. J., Sandstrom, R., Shafer, A., Vetrie, D., Weaver, M., Wilcox, S., Yu, M., Collins, F. S., Dekker, J., Lieb, J. D., Tullius, T. D., Crawford, G. E., Sunyaev, S., Noble, W. S., Dunham, I., Denoeud, F., Reymond, A., Kapranov, P., Rozowsky, J., Zheng, D., Castelo, R., Frankish, A., Harrow, J., Ghosh, S., Sandelin, A., Hofacker, I. L., Baertsch, R., Keefe, D., Dike, S., Cheng, J., Hirsch, H. A., Sekinger, E. A., Lagarde, J., Abril, J. F., Shahab, A., Flamm, C., Fried, C., Hackermuller, J., Hertel, J., Lindemeyer, M., Missal, K., Tanzer, A., Washietl, S., Korbel, J., Emanuelsson, O., Pedersen, J. S., Holroyd, N., Taylor, R., Swarbreck, D., Matthews, N., Dickson, M. C., Thomas, D. J., Weirauch, M. T., Gilbert, J., Drenkow, J., Bell, I., Zhao, X., Srinivasan, K. G., Sung, W. K., Ooi, H. S., Chiu, K. P., Foissac, S., Alioto, T., Brent, M., Pachter, L., Tress, M. L., Valencia, A., Choo, S. W., Choo, C. Y., Ucla, C., Manzano, C., Wyss, C., Cheung, E., Clark, T. G., Brown, J. B., Ganesh, M., Patel, S., Tammana, H., Chrast, J., Henrichsen, C. N., Kai, C., Kawai, J., Nagalakshmi, U., Wu, J., Lian, Z., Lian, J., Newburger, P., Zhang, X., Bickel, P., Mattick, J. S., Carninci, P., Hayashizaki, Y., Weissman, S., Hubbard, T., Myers, R. M., Rogers, J., Stadler, P. F., Lowe, T. M., Wei, C. L., Ruan, Y., Struhl, K., Gerstein, M., Antonarakis, S. E., Fu, Y., Green, E. D., Karaoz, U., Siepel, A., Taylor, J., Liefer, L. A., Wetterstrand, K. A., Good, P. J., Feingold, E. A., Guyer, M. S., Cooper, G. M., Asimenos, G., Dewey, C. N., Hou, M., Nikolaev, S., Montoya-Burgos, J. I., Loytynoja, A., Whelan, S., Pardi, F., Massingham, T., Huang, H., Zhang, N. R., Holmes, I., Mullikin, J. C., Ureta-Vidal, A., Paten, B., Seringhaus, M., Church, D., Rosenbloom, K., Kent, W. J., Stone, E. A., Batzoglou, S., Goldman, N., Hardison, R. C., Haussler, D., Miller, W., Sidow, A., Trinklein, N. D., Zhang, Z. D., Barrera, L., Stuart, R., King, D. C., Ameur, A., Enroth, S., Bieda, M. C., Kim, J., Bhinge, A. A., Jiang, N., Liu, J., Yao, F., Vega, V. B., Lee, C. W., Ng, P., Yang, A., Moqtaderi, Z., Zhu, Z., Xu, X., Squazzo, S., Oberley, M. J., Inman, D., Singer, M. A., Richmond, T. A., Munn, K. J., Rada-Iglesias, A., Wallerman, O., Komorowski, J., Fowler, J. C., Couttet, P., Bruce, A. W., Dovey, O. M., Ellis, P. D., Langford, C. F., Nix, D. A., Euskirchen, G., Hartman, S., Urban, A. E., Kraus, P., Van Calcar, S., Heintzman, N., Kim, T. H., Wang, K., Qu, C., Hon, G., Luna, R., Glass, C. K., Rosenfeld, M. G., Aldred, S. F., Cooper, S. J., Halees, A., Lin, J. M., Shulha, H. P., Xu, M., Haidar, J. N., Yu, Y., Iyer, V. R., Green, R. D., Wadelius, C., Farnham, P. J., Ren, B., Harte, R. A., Hinrichs, A. S., Trumbower, H., Clawson, H., Hillman-Jackson, J., Zweig, A. S., Smith, K., Thakkapallayil, A., Barber, G., Kuhn, R. M., Karolchik, D., Armengol, L., Bird, C. P., de Bakker, P. I., Kern, A. D., Lopez-Bigas, N., Martin, J. D., Stranger, B. E., Woodroffe, A., Davydov, E., Dimas, A., Eyras, E., Hallgrimsdottir, I. B., Huppert, J., Zody, M. C., Abecasis, G. R., Estivill, X., Bouffard, G. G., Guan, X., Hansen, N. F., Idol, J. R., Maduro, V. V., Maskeri, B., McDowell, J. C., Park, M., Thomas, P. J., Young, A. C., Blakesley, R. W., Muzny, D. M., Sodergren, E., Wheeler, D. A., Worley, K. C., Jiang, H., Weinstock, G. M., Gibbs, R. A., Graves, T., Fulton, R., Mardis, E. R., Wilson, R. K., Clamp, M., Cuff, J., Gnerre, S., Jaffe, D. B., Chang, J. L., Lindblad-Toh, K., Lander, E. S., Koriabine, M., Nefedov, M., Osoegawa, K., Yoshinaga, Y., Zhu, B., and de Jong, P. J. (2007). Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816.
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXms1Wjsb0%3D&md5=a555b24d1f7ecaffdc3cc13f8aa46d53CAS | 17571346PubMed |

Brawand, D., Soumillon, M., Necsulea, A., Julien, P., Csardi, G., Harrigan, P., Weier, M., Liechti, A., Aximu-Petri, A., Kircher, M., Albert, F. W., Zeller, U., Khaitovich, P., Grutzner, F., Bergmann, S., Nielsen, R., Paabo, S., and Kaessmann, H. (2011). The evolution of gene expression levels in mammalian organs. Nature 478, 343–348.
The evolution of gene expression levels in mammalian organs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlChtrfF&md5=ccb3dafa1488f10d65fe470a55bae072CAS | 22012392PubMed |

Cock, P. J., Fields, C. J., Goto, N., Heuer, M. L., and Rice, P. M. (2010). The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants. Nucleic Acids Res. 38, 1767–1771.
The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXkt1Oqurc%3D&md5=d657e0f1d46da83ee8ba3afe283ab425CAS | 20015970PubMed |

Coleman, S. J., Zeng, Z., Wang, K., Luo, S., Khrebtukova, I., Mienaltowski, M. J., Schroth, G. P., Liu, J., and MacLeod, J. N. (2010). Structural annotation of equine protein-coding genes determined by mRNA sequencing. Anim. Genet. 41, 121–130.
Structural annotation of equine protein-coding genes determined by mRNA sequencing.Crossref | GoogleScholarGoogle Scholar | 21070285PubMed |

Culhane, A. C., Thioulouse, J., Perriere, G., and Higgins, D. G. (2005). MADE4: an R package for multivariate analysis of gene expression data. Bioinformatics 21, 2789–2790.
MADE4: an R package for multivariate analysis of gene expression data.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXks1eru7g%3D&md5=0c7b8f608ef65dc6cfd685e7271eb9ecCAS | 15797915PubMed |

Eddy, S. R. (2012). The C-value Paradox, junk DNA and ENCODE. Curr. Biol. 22, R898–R899.
The C-value Paradox, junk DNA and ENCODE.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs1aqtrnK&md5=96e0f37aa2a1b78044739469b3eccfbaCAS | 23137679PubMed |

Edgar, R., Domrachev, M., and Lash, A. E. (2002). Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210.
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xht12kurs%3D&md5=16d950d0398d5934846e8cb789e39e96CAS | 11752295PubMed |

Egli, M., Leeners, B., and Kruger, T. H. (2010). Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction. Reproduction 140, 643–654.
Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFCnsbfO&md5=7b3d61f3a6dd0e820d51459e8bf95388CAS | 20733016PubMed |

Eisenberg, E., and Levanon, E. Y. (2003). Human housekeeping genes are compact. Trends Genet. 19, 362–365.
Human housekeeping genes are compact.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXlt1eitLc%3D&md5=24e3886cdf9eab24916fcb220b70a89aCAS | 12850439PubMed |

Elsik, C. G., Tellam, R. L., Worley, K. C., Gibbs, R. A., Muzny, D. M., Weinstock, G. M., Adelson, D. L., Eichler, E. E., Elnitski, L., Guigo, R., Hamernik, D. L., Kappes, S. M., Lewin, H. A., Lynn, D. J., Nicholas, F. W., Reymond, A., Rijnkels, M., Skow, L. C., Zdobnov, E. M., Schook, L., Womack, J., Alioto, T., Antonarakis, S. E., Astashyn, A., Chapple, C. E., Chen, H. C., Chrast, J., Camara, F., Ermolaeva, O., Henrichsen, C. N., Hlavina, W., Kapustin, Y., Kiryutin, B., Kitts, P., Kokocinski, F., Landrum, M., Maglott, D., Pruitt, K., Sapojnikov, V., Searle, S. M., Solovyev, V., Souvorov, A., Ucla, C., Wyss, C., Anzola, J. M., Gerlach, D., Elhaik, E., Graur, D., Reese, J. T., Edgar, R. C., McEwan, J. C., Payne, G. M., Raison, J. M., Junier, T., Kriventseva, E. V., Eyras, E., Plass, M., Donthu, R., Larkin, D. M., Reecy, J., Yang, M. Q., Chen, L., Cheng, Z., Chitko-McKown, C. G., Liu, G. E., Matukumalli, L. K., Song, J., Zhu, B., Bradley, D. G., Brinkman, F. S., Lau, L. P., Whiteside, M. D., Walker, A., Wheeler, T. T., Casey, T., German, J. B., Lemay, D. G., Maqbool, N. J., Molenaar, A. J., Seo, S., Stothard, P., Baldwin, C. L., Baxter, R., Brinkmeyer-Langford, C. L., Brown, W. C., Childers, C. P., Connelley, T., Ellis, S. A., Fritz, K., Glass, E. J., Herzig, C. T., Iivanainen, A., Lahmers, K. K., Bennett, A. K., Dickens, C. M., Gilbert, J. G., Hagen, D. E., Salih, H., Aerts, J., Caetano, A. R., Dalrymple, B., Garcia, J. F., Gill, C. A., Hiendleder, S. G., Memili, E., Spurlock, D., Williams, J. L., Alexander, L., Brownstein, M. J., Guan, L., Holt, R. A., Jones, S. J., Marra, M. A., Moore, R., Moore, S. S., Roberts, A., Taniguchi, M., Waterman, R. C., Chacko, J., Chandrabose, M. M., Cree, A., Dao, M. D., Dinh, H. H., Gabisi, R. A., Hines, S., Hume, J., Jhangiani, S. N., Joshi, V., Kovar, C. L., Lewis, L. R., Liu, Y. S., Lopez, J., Morgan, M. B., Nguyen, N. B., Okwuonu, G. O., Ruiz, S. J., Santibanez, J., Wright, R. A., Buhay, C., Ding, Y., Dugan-Rocha, S., Herdandez, J., Holder, M., Sabo, A., Egan, A., Goodell, J., Wilczek-Boney, K., Fowler, G. R., Hitchens, M. E., Lozado, R. J., Moen, C., Steffen, D., Warren, J. T., Zhang, J., Chiu, R., Schein, J. E., Durbin, K. J., Havlak, P., Jiang, H., Liu, Y., Qin, X., Ren, Y., Shen, Y., Song, H., Bell, S. N., Davis, C., Johnson, A. J., Lee, S., Nazareth, L. V., Patel, B. M., Pu, L. L., Vattathil, S., Williams, R. L., Curry, S., Hamilton, C., Sodergren, E., Wheeler, D. A., Barris, W., Bennett, G. L., Eggen, A., Green, R. D., Harhay, G. P., Hobbs, M., Jann, O., Keele, J. W., Kent, M. P., Lien, S., McKay, S. D., McWilliam, S., Ratnakumar, A., Schnabel, R. D., Smith, T., Snelling, W. M., Sonstegard, T. S., Stone, R. T., Sugimoto, Y., Takasuga, A., Taylor, J. F., Van Tassell, C. P., Macneil, M. D., Abatepaulo, A. R., Abbey, C. A., Ahola, V., Almeida, I. G., Amadio, A. F., Anatriello, E., Bahadue, S. M., Biase, F. H., Boldt, C. R., Carroll, J. A., Carvalho, W. A., Cervelatti, E. P., Chacko, E., Chapin, J. E., Cheng, Y., Choi, J., Colley, A. J., de Campos, T. A., De Donato, M., Santos, I. K., de Oliveira, C. J., Deobald, H., Devinoy, E., Donohue, K. E., Dovc, P., Eberlein, A., Fitzsimmons, C. J., Franzin, A. M., Garcia, G. R., Genini, S., Gladney, C. J., Grant, J. R., Greaser, M. L., Green, J. A., Hadsell, D. L., Hakimov, H. A., Halgren, R., Harrow, J. L., Hart, E. A., Hastings, N., Hernandez, M., Hu, Z. L., Ingham, A., Iso-Touru, T., Jamis, C., Jensen, K., Kapetis, D., Kerr, T., Khalil, S. S., Khatib, H., Kolbehdari, D., Kumar, C. G., Kumar, D., Leach, R., Lee, J. C., Li, C., Logan, K. M., Malinverni, R., Marques, E., Martin, W. F., Martins, N. F., Maruyama, S. R., Mazza, R., McLean, K. L., Medrano, J. F., Moreno, B. T., More, D. D., Muntean, C. T., Nandakumar, H. P., Nogueira, M. F., Olsaker, I., Pant, S. D., Panzitta, F., Pastor, R. C., Poli, M. A., Poslusny, N., Rachagani, S., Ranganathan, S., Razpet, A., Riggs, P. K., Rincon, G., Rodriguez-Osorio, N., Rodriguez-Zas, S. L., Romero, N. E., Rosenwald, A., Sando, L., Schmutz, S. M., Shen, L., Sherman, L., Southey, B. R., Lutzow, Y. S., Sweedler, J. V., Tammen, I., Telugu, B. P., Urbanski, J. M., Utsunomiya, Y. T., Verschoor, C. P., Waardenberg, A. J., Wang, Z., Ward, R., Weikard, R., Welsh, T. H., White, S. N., Wilming, L. G., Wunderlich, K. R., Yang, J., and Zhao, F. Q. (2009). The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science 324, 522–528.
The genome sequence of taurine cattle: a window to ruminant biology and evolution.Crossref | GoogleScholarGoogle Scholar | 19390049PubMed |

ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74.
An integrated encyclopedia of DNA elements in the human genome.Crossref | GoogleScholarGoogle Scholar | 22955616PubMed |

Flicek, P., Amode, M. R., Barrell, D., Beal, K., Brent, S., Carvalho-Silva, D., Clapham, P., Coates, G., Fairley, S., Fitzgerald, S., Gil, L., Gordon, L., Hendrix, M., Hourlier, T., Johnson, N., Kahari, A. K., Keefe, D., Keenan, S., Kinsella, R., Komorowska, M., Koscielny, G., Kulesha, E., Larsson, P., Longden, I., McLaren, W., Muffato, M., Overduin, B., Pignatelli, M., Pritchard, B., Riat, H. S., Ritchie, G. R., Ruffier, M., Schuster, M., Sobral, D., Tang, Y. A., Taylor, K., Trevanion, S., Vandrovcova, J., White, S., Wilson, M., Wilder, S. P., Aken, B. L., Birney, E., Cunningham, F., Dunham, I., Durbin, R., Fernandez-Suarez, X. M., Harrow, J., Herrero, J., Hubbard, T. J., Parker, A., Proctor, G., Spudich, G., Vogel, J., Yates, A., Zadissa, A., and Searle, S. M. (2012). Ensembl 2012. Nucleic Acids Res. 40, D84–D90.
Ensembl 2012.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs12htb%2FK&md5=50dec39d2b3074f3b91ee6c3492795e7CAS | 22086963PubMed |

Foley, C., Chapwanya, A., Creevey, C., Narciandi, F., Morris, D., Kenny, E., Cormican, P., Callanan, J. J., O’Farrelly, C., and Meade, K. G. (2012). Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows. BMC Genomics 13, 489.
Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXjsVamtL8%3D&md5=b745f5c840ce86438f895b3c51360590CAS | 22985206PubMed |

Forde, N., Duffy, G. B., McGettigan, P. A., Browne, J. A., Prakash Mehta, J., Kelly, A. K., Mansouri-Attia, N., Sandra, O., Loftus, B. J., Crowe, M. A., Fair, T., Roche, J. F., Lonergan, P., and Evans, A. C. (2012). Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiol. Genomics 44, 799–810.
Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhslamuw%3D%3D&md5=1ccaf9ba21f6e914cf4b94c5342c23d1CAS | 22759920PubMed |

Freeman, T. C., Ivens, A., Baillie, J. K., Beraldi, D., Barnett, M. W., Dorward, D., Downing, A., Fairbairn, L., Kapetanovic, R., Raza, S., Tomoiu, A., Alberio, R., Wu, C., Su, A. I., Summers, K. M., Tuggle, C. K., Archibald, A. L., and Hume, D. A. (2012). A gene expression atlas of the domestic pig. BMC Biol. 10, 90.
A gene expression atlas of the domestic pig.Crossref | GoogleScholarGoogle Scholar | 23153189PubMed |

Gini, C. (1912). ‘Variabilità e mutabilità.’ (Bologna, Italy.)

Handcock, M. S., and Morris, M. (1999). ‘Relative Distribution Methods in the Social Sciences.’ Statistics for Social Science and Public Policy Series. (Springer: New York.)

Harhay, G. P., Smith, T. P., Alexander, L. J., Haudenschild, C. D., Keele, J. W., Matukumalli, L. K., Schroeder, S. G., Van Tassell, C. P., Gresham, C. R., Bridges, S. M., Burgess, S. C., and Sonstegard, T. S. (2010). An atlas of bovine gene expression reveals novel distinctive tissue characteristics and evidence for improving genome annotation. Genome Biol. 11, R102.
An atlas of bovine gene expression reveals novel distinctive tissue characteristics and evidence for improving genome annotation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVahs7bM&md5=04916703d84c558bdd7e6c0a4b26902eCAS | 20961407PubMed |

Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., Abajian, C., Beckmann, C. F., Bernard, A., Bertagnolli, D., Boe, A. F., Cartagena, P. M., Chakravarty, M. M., Chapin, M., Chong, J., Dalley, R. A., Daly, B. D., Dang, C., Datta, S., Dee, N., Dolbeare, T. A., Faber, V., Feng, D., Fowler, D. R., Goldy, J., Gregor, B. W., Haradon, Z., Haynor, D. R., Hohmann, J. G., Horvath, S., Howard, R. E., Jeromin, A., Jochim, J. M., Kinnunen, M., Lau, C., Lazarz, E. T., Lee, C., Lemon, T. A., Li, L., Li, Y., Morris, J. A., Overly, C. C., Parker, P. D., Parry, S. E., Reding, M., Royall, J. J., Schulkin, J., Sequeira, P. A., Slaughterbeck, C. R., Smith, S. C., Sodt, A. J., Sunkin, S. M., Swanson, B. E., Vawter, M. P., Williams, D., Wohnoutka, P., Zielke, H. R., Geschwind, D. H., Hof, P. R., Smith, S. M., Koch, C., Grant, S. G., and Jones, A. R. (2012). An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399.
An anatomically comprehensive atlas of the adult human brain transcriptome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtlymu77N&md5=866652f8580ce231ad8e718d672c615dCAS | 22996553PubMed |

Hsiao, L. L., Dangond, F., Yoshida, T., Hong, R., Jensen, R. V., Misra, J., Dillon, W., Lee, K. F., Clark, K. E., Haverty, P., Weng, Z., Mutter, G. L., Frosch, M. P., MacDonald, M. E., Milford, E. L., Crum, C. P., Bueno, R., Pratt, R. E., Mahadevappa, M., Warrington, J. A., Stephanopoulos, G., and Gullans, S. R. (2001). A compendium of gene expression in normal human tissues. Physiol. Genomics 7, 97–104.
A compendium of gene expression in normal human tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFagsLs%3D&md5=76b9c668c0cd7095567f95032eaa6cacCAS | 11773596PubMed |

Huang, D. W., Sherman, B. T., and Lempicki, R. A. (2009). Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1–13.
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.Crossref | GoogleScholarGoogle Scholar |

Huber, W., Carey, V. J., Gentleman, R., Anders, S., Carlson, M., Carvalho, B. S., Corrada Bravo, H., Davis, S., Gatto, L., Girke, T., Gottardo, R., Hahne, F., Hansen, K. D., Irizarry, R. A., Lawrence, M., Love, M. I., MacDonald, J., Obenchain, V., Oleś, A. J., Pagès, H., Reyes, A., Shannon, P., Smyth, G. K., Tenenbaum, D., Waldron, L., and Morgan, M. (2015). Orchestrating high-throughput genomic analysis with Bioconductor. Nat. Methods 12, 115–121.
Orchestrating high-throughput genomic analysis with Bioconductor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXjvVCrurg%3D&md5=323cd893de45113e1156ee03829f5546CAS | 25633503PubMed |

Keibler, E., and Brent, M. R. (2003). Eval: a software package for analysis of genome annotations. BMC Bioinformatics 4, 50.
Eval: a software package for analysis of genome annotations.Crossref | GoogleScholarGoogle Scholar | 14565849PubMed |

Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., and Haussler, D. (2002). The human genome browser at UCSC. Genome Res. 12, 996–1006.
The human genome browser at UCSC.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xks12hs7s%3D&md5=76682dcf499587d9d0b5a439bd6f32a5CAS | 12045153PubMed |

Lawrence, M., Gentleman, R., and Carey, V. (2009). rtracklayer: an R package for interfacing with genome browsers. Bioinformatics 25, 1841–1842.
rtracklayer: an R package for interfacing with genome browsers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXot1Cjt7c%3D&md5=e8e288fe6191b2829702608740cfb873CAS | 19468054PubMed |

Lawrence, M., Huber, W., Pagès, H., Aboyoun, P., Carlson, M., Gentleman, R., Morgan, M., and Carey, V. (2013). Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118.
Software for computing and annotating genomic ranges.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVensr%2FK&md5=8385ffd4f8ad7d38dc844cec8c86c1d6CAS | 23950696PubMed |

Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., Chen, L., Chen, T. M., Chin, M. C., Chong, J., Crook, B. E., Czaplinska, A., Dang, C. N., Datta, S., Dee, N. R., Desaki, A. L., Desta, T., Diep, E., Dolbeare, T. A., Donelan, M. J., Dong, H. W., Dougherty, J. G., Duncan, B. J., Ebbert, A. J., Eichele, G., Estin, L. K., Faber, C., Facer, B. A., Fields, R., Fischer, S. R., Fliss, T. P., Frensley, C., Gates, S. N., Glattfelder, K. J., Halverson, K. R., Hart, M. R., Hohmann, J. G., Howell, M. P., Jeung, D. P., Johnson, R. A., Karr, P. T., Kawal, R., Kidney, J. M., Knapik, R. H., Kuan, C. L., Lake, J. H., Laramee, A. R., Larsen, K. D., Lau, C., Lemon, T. A., Liang, A. J., Liu, Y., Luong, L. T., Michaels, J., Morgan, J. J., Morgan, R. J., Mortrud, M. T., Mosqueda, N. F., Ng, L. L., Ng, R., Orta, G. J., Overly, C. C., Pak, T. H., Parry, S. E., Pathak, S. D., Pearson, O. C., Puchalski, R. B., Riley, Z. L., Rockett, H. R., Rowland, S. A., Royall, J. J., Ruiz, M. J., Sarno, N. R., Schaffnit, K., Shapovalova, N. V., Sivisay, T., Slaughterbeck, C. R., Smith, S. C., Smith, K. A., Smith, B. I., Sodt, A. J., Stewart, N. N., Stumpf, K. R., Sunkin, S. M., Sutram, M., Tam, A., Teemer, C. D., Thaller, C., Thompson, C. L., Varnam, L. R., Visel, A., Whitlock, R. M., Wohnoutka, P. E., Wolkey, C. K., Wong, V. Y., Wood, M., Yaylaoglu, M. B., Young, R. C., Youngstrom, B. L., Yuan, X. F., Zhang, B., Zwingman, T. A., and Jones, A. R. (2007). Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176.
Genome-wide atlas of gene expression in the adult mouse brain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtFKjtw%3D%3D&md5=b072423e965485199b853dec772d9a83CAS | 17151600PubMed |

Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., and Durbin, R. (2009). The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079.
The Sequence Alignment/Map format and SAMtools.Crossref | GoogleScholarGoogle Scholar | 19505943PubMed |

Li, B., Ruotti, V., Stewart, R. M., Thomson, J. A., and Dewey, C. N. (2010). RNA-Seq gene expression estimation with read mapping uncertainty. Bioinformatics 26, 493–500.
RNA-Seq gene expression estimation with read mapping uncertainty.Crossref | GoogleScholarGoogle Scholar | 20022975PubMed |

Lovén, J., Orlando, D. A., Sigova, A. A., Lin, C. Y., Rahl, P. B., Burge, C. B., Levens, D. L., Lee, T. I., and Young, R. A. (2012). Revisiting global gene expression analysis. Cell 151, 476–482.
Revisiting global gene expression analysis.Crossref | GoogleScholarGoogle Scholar | 23101621PubMed |

Mamo, S., Mehta, J. P., McGettigan, P., Fair, T., Spencer, T. E., Bazer, F. W., and Lonergan, P. (2011). RNA sequencing reveals novel gene clusters in bovine conceptuses associated with maternal recognition of pregnancy and implantation. Biol. Reprod. 85, 1143–1151.
RNA sequencing reveals novel gene clusters in bovine conceptuses associated with maternal recognition of pregnancy and implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1ShsLbO&md5=5fb51a79845f3282dd2de87af18012f1CAS | 21795669PubMed |

McCabe, M., Waters, S., Morris, D., Kenny, D., Lynn, D., and Creevey, C. (2012). RNA-seq analysis of differential gene expression in liver from lactating dairy cows divergent in negative energy balance. BMC Genomics 13, 193.
RNA-seq analysis of differential gene expression in liver from lactating dairy cows divergent in negative energy balance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhslGqu7rL&md5=71e0f22f48ea85c7ad06891d00e97027CAS | 22607119PubMed |

Morozov, I. Y., Jones, M. G., Gould, P. D., Crome, V., Wilson, J. B., Hall, A. J., Rigden, D. J., and Caddick, M. X. (2012). mRNA 3′ tagging is induced by nonsense-mediated decay and promotes ribosome dissociation. Mol. Cell. Biol. 32, 2585–2595.
mRNA 3′ tagging is induced by nonsense-mediated decay and promotes ribosome dissociation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XpsVyksLg%3D&md5=f9244eb7b4444736111ea5f8d9a9fa2aCAS | 22547684PubMed |

Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., and Wold, B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 5, 621–628.
Mapping and quantifying mammalian transcriptomes by RNA-Seq.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnslyqs7k%3D&md5=0fd254b12f8780b5a830bdfd2446584cCAS | 18516045PubMed |

O’Loughlin, A., Lynn, D. J., McGee, M., Doyle, S., McCabe, M., and Earley, B. (2012). Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology. BMC Genomics 13, 250.
Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhslamu7%2FN&md5=84c728bb8f75a087cac0e206800e0517CAS | 22708644PubMed |

Pearson, R. D., Liu, X., Sanguinetti, G., Milo, M., Lawrence, N. D., and Rattray, M. (2009). puma: a Bioconductor package for propagating uncertainty in microarray analysis. BMC Bioinformatics 10, 211.
puma: a Bioconductor package for propagating uncertainty in microarray analysis.Crossref | GoogleScholarGoogle Scholar | 19589155PubMed |

Pluta, K., McGettigan, P. A., Reid, C. J., Browne, J. A., Irwin, J. A., Tharmalingam, T., Corfield, A., Baird, A. W., Loftus, B. J., Evans, A. C., and Carrington, S. D. (2012). Molecular aspects of mucin biosynthesis and mucus formation in the bovine cervix during the periestrous period. Physiol. Genomics 44, 1165–1178.
Molecular aspects of mucin biosynthesis and mucus formation in the bovine cervix during the periestrous period.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXivVynu7g%3D&md5=94e1033690cc8009cc8861bf874d9ce6CAS | 23092952PubMed |

Quinlan, A. R., and Hall, I. M. (2010). BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842.
BEDTools: a flexible suite of utilities for comparing genomic features.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXivFGkurc%3D&md5=037a4e1bef71499ec951c94ac9d44728CAS | 20110278PubMed |

Robinson, J. T., Thorvaldsdottir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., and Mesirov, J. P. (2011). Integrative genomics viewer. Nat. Biotechnol. 29, 24–26.
Integrative genomics viewer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjsFWrtg%3D%3D&md5=49443e0ecbb0bf06fcb6045d66731463CAS | 21221095PubMed |

Schug, J., Schuller, W. P., Kappen, C., Salbaum, J. M., Bucan, M., and Stoeckert, C. J. (2005). Promoter features related to tissue specificity as measured by Shannon entropy. Genome Biol. 6, R33.
Promoter features related to tissue specificity as measured by Shannon entropy.Crossref | GoogleScholarGoogle Scholar | 15833120PubMed |

Shannon, C. E., and Weaver, W. (1949). ‘The Mathematical Theory of Communication.’ (University of Illinois Press: Urbana, IL.)

Siddiqui, A. S., Khattra, J., Delaney, A. D., Zhao, Y., Astell, C., Asano, J., Babakaiff, R., Barber, S., Beland, J., Bohacec, S., Brown-John, M., Chand, S., Charest, D., Charters, A. M., Cullum, R., Dhalla, N., Featherstone, R., Gerhard, D. S., Hoffman, B., Holt, R. A., Hou, J., Kuo, B. Y., Lee, L. L., Lee, S., Leung, D., Ma, K., Matsuo, C., Mayo, M., McDonald, H., Prabhu, A. L., Pandoh, P., Riggins, G. J., de Algara, T. R., Rupert, J. L., Smailus, D., Stott, J., Tsai, M., Varhol, R., Vrljicak, P., Wong, D., Wu, M. K., Xie, Y. Y., Yang, G., Zhang, I., Hirst, M., Jones, S. J., Helgason, C. D., Simpson, E. M., Hoodless, P. A., and Marra, M. A. (2005). A mouse atlas of gene expression: large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells. Proc. Natl Acad. Sci. USA 102, 18 485–18 490.
A mouse atlas of gene expression: large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Kl&md5=89c25a3ccf2d6044e4dd513a24159f04CAS |

Smyth, G. K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology 3, Article3.
Linear models and empirical bayes methods for assessing differential expression in microarray experiments.Crossref | GoogleScholarGoogle Scholar | 16646809PubMed |

Stocco, C. (2008). Aromatase expression in the ovary: hormonal and molecular regulation. Steroids 73, 473–487.
Aromatase expression in the ovary: hormonal and molecular regulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjtlemu74%3D&md5=21390f597481a491e1c1df07cfc6382eCAS | 18321551PubMed |

Struhl, K. (2007). Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat. Struct. Mol. Biol. 14, 103–105.
Transcriptional noise and the fidelity of initiation by RNA polymerase II.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Gqurs%3D&md5=11510d0d11c1fa72f05025cfc648ad47CAS | 17277804PubMed |

Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., Cooke, M. P., Walker, J. R., and Hogenesch, J. B. (2004). A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl Acad. Sci. USA 101, 6062–6067.
A gene atlas of the mouse and human protein-encoding transcriptomes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjsFKntr4%3D&md5=9fdd0ba9617e4bac588b95d5e65074beCAS | 15075390PubMed |

Trapnell, C., Pachter, L., and Salzberg, S. L. (2009). TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105–1111.
TopHat: discovering splice junctions with RNA-Seq.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltFWisrk%3D&md5=19838d5c0624e50070732fe5c4acfd48CAS | 19289445PubMed |

Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., and Pachter, L. (2010). Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511–515.
Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlsVyitLY%3D&md5=54d49a389761d2050915ef17f228ab95CAS | 20436464PubMed |

van Bakel, H., Nislow, C., Blencowe, B. J., and Hughes, T. R. (2010). Most ‘dark matter’ transcripts are associated with known genes. PLoS Biol. 8, e1000371.
Most ‘dark matter’ transcripts are associated with known genes.Crossref | GoogleScholarGoogle Scholar | 20502517PubMed |

Walsh, S. W., Mehta, J. P., McGettigan, P. A., Browne, J. A., Forde, N., Alibrahim, R. M., Mulligan, F. J., Loftus, B., Crowe, M. A., Matthews, D., Diskin, M., Mihm, M., and Evans, A. C. (2012). Effect of the metabolic environment at key stages of follicle development in cattle: focus on steroid biosynthesis. Physiol. Genomics 44, 504–517.
Effect of the metabolic environment at key stages of follicle development in cattle: focus on steroid biosynthesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsVKjurbP&md5=5f47a861ab2d727321aacf857a410bfbCAS | 22414914PubMed |

Warrington, J. A., Nair, A., Mahadevappa, M., and Tsyganskaya, M. (2000). Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes. Physiol. Genomics 2, 143–147.
| 1:CAS:528:DC%2BD3cXltFKns70%3D&md5=8aaaa064fb242f3c4137a9ad28ac17e8CAS | 11015593PubMed |

Wasserman, W. W., and Fickett, J. W. (1998). Identification of regulatory regions which confer muscle-specific gene expression. J. Mol. Biol. 278, 167–181.
Identification of regulatory regions which confer muscle-specific gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjt1artr8%3D&md5=d1a34dcec91cd16f83b40be5fbc6dddfCAS | 9571041PubMed |

Witten, D. M., and Tibshirani, R. (2013). ‘Sparcl: Perform sparse hierarchical clustering and sparse k-means clustering. R package version 1.0.3.’ Available at http://CRAN.R-project.org/package=sparcl [Accessed 9 September 2015]