379 results on '"Goddard, Michael"'
Search Results
52. Estimating Effects and Making Predictions from Genome-Wide Marker Data
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Goddard, Michael E., Wray, Naomi R., Verbyla, Klara, and Visscher, Peter M.
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- 2009
53. Genes influencing milk production traits predominantly affect one of four biological pathways
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Goddard Michael, McPartlan Helen, and Chamberlain Amanda
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bivariate analysis ,independent traits ,pleiotropy ,genome scan ,false discovery rate ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract In this study we introduce a method that accounts for false positive and false negative results in attempting to estimate the true proportion of quantitative trait loci that affect two different traits. This method was applied to data from a genome scan that was used to detect QTL for three independent milk production traits, Australian Selection Index (ASI), protein percentage (P%) and fat percentage corrected for protein percentage (F% – P%). These four different scenarios are attributed to four biological pathways: QTL that (1) increase or decrease total mammary gland production (affecting ASI only); (2) increase or decrease lactose synthesis resulting in the volume of milk being changed but without a change in protein or fat yield (affecting P% only); (3) increase or decrease protein synthesis while milk volume remains relatively constant (affecting ASI and P% in the same direction); (4) increase or decrease fat synthesis while the volume of milk remains relatively constant (affecting F% – P% only). The results indicate that of the positions that detected a gene, most affected one trait and not the others, though a small proportion (2.8%) affected ASI and P% in the same direction.
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- 2008
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54. Can Scientists and Policy Makers Work Together?
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Choi, Bernard C. K., Pang, Tikki, Lin, Vivian, Puska, Pekka, Sherman, Gregory, Goddard, Michael, Ackland, Michael J., Sainsbury, Peter, Stachenko, Sylvie, Morrison, Howard, and Clottey, Clarence
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- 2005
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55. Empirical evaluation of selective DNA pooling to map QTL in dairy cattle using a half-sib design by comparison to individual genotyping and interval mapping
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Robinson Nicholas, Mariasegaram Maxy, and Goddard Michael
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selective DNA pooling ,dairy half-sib design ,genome scan ,individual selective genotyping ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract This study represents the first attempt at an empirical evaluation of the DNA pooling methodology by comparing it to individual genotyping and interval mapping to detect QTL in a dairy half-sib design. The findings indicated that the use of peak heights from the pool electropherograms without correction for stutter (shadow) product and preferential amplification performed as well as corrected estimates of frequencies. However, errors were found to decrease the power of the experiment at every stage of the pooling and analysis. The main sources of errors include technical errors from DNA quantification, pool construction, inconsistent differential amplification, and from the prevalence of sire alleles in the dams. Additionally, interval mapping using individual genotyping gains information from phenotypic differences between individuals in the same pool and from neighbouring markers, which is lost in a DNA pooling design. These errors cause some differences between the markers detected as significant by pooling and those found significant by interval mapping based on individual selective genotyping. Therefore, it is recommended that pooled genotyping only be used as part of an initial screen with significant results to be confirmed by individual genotyping. Strategies for improving the efficiency of the DNA pooling design are also presented.
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- 2007
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56. Research and Rhetoric on Women in Papua New Guinea's Village Courts
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Goddard, Michael
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- 2005
57. Identification of Genomic Variants Causing Variation in Quantitative Traits: A Review.
- Author
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Meuwissen, Theo, Hayes, Ben, MacLeod, Iona, and Goddard, Michael
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LINKAGE disequilibrium ,NUCLEOTIDE sequence ,LOCUS (Genetics) ,GENOME editing ,DNA sequencing - Abstract
Many of the important traits of livestock are complex or quantitative traits controlled by thousands of variants in the DNA sequence of individual animals and environmental factors. Identification of these causal variants would be advantageous for genomic prediction, to understand the physiology and evolution of important traits and for genome editing. However, it is difficult to identify these causal variants because their effects are small and they are in linkage disequilibrium with other DNA variants. Nevertheless, it should be possible to identify probable causal variants for complex traits just as we do for simple traits provided we compensate for the small effect size with larger sample size. In this review we consider eight types of evidence needed to identify causal variants. Large and diverse samples of animals, accurate genotypes, multiple phenotypes, annotation of genomic sites, comparisons across species, comparisons across the genome, the physiological role of candidate genes and experimental mutation of the candidate genomic site. [ABSTRACT FROM AUTHOR]
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- 2022
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58. Reto's Chance: State and Status in an Urban Papua New Guinea Settlement
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Goddard, Michael
- Published
- 2002
59. Rethinking Western Motu Descent Groups
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Goddard, Michael
- Published
- 2001
60. Genetic studies of body mass index yield new insights for obesity biology
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Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jianʼan, Mägi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J., Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L., Böttcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E., de Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathias, Grabe, Hans-Jörgen, Grallert, Harald, Grammer, Tanja B., Gräler, Jürgen, Grönberg, Henrik, Groves, Christopher J., Gusto, Gaëlle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L., Helmer, Quinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L., Jeff, Janina M., Johansson, Åsa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Sin Lo, Ken, Lobbens, Stéphane, Lorbeer, Roberto, Lu, Yingchang, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Nöthen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thomas, Shi, Jianxin, Vernon Smith, Albert, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wright, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco-Cereceda, Anders, Gådin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McCarroll, Steven A., McKnight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, vanʼt Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Adrienne Cupples, L., Cusi, Daniele, Danesh, John, de Faire, Ulf, den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrières, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Kees Hovingh, G., Humphries, Steve E., Hunt, Steven C., Hyppönen, Elina, Illig, Thomas, Jacobs, Kevin B., Jarvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Wouter Jukema, J., Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Trégouët, David-Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Willemsen, Gonneke, Witteman, Jacqueline C., Carola Zillikens, M., Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stéphane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., de Bakker, Paul I. W., Dedoussis, George, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Groop, Leif C., Haiman, Christopher A., Hamsten, Anders, Hui, Jennie, Hunter, David J., Hveem, Kristian, Kaplan, Robert C., Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G., März, Winfried, Melbye, Mads, Metspalu, Andres, Moebus, Susanne, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Schadt, Eric E., Schlessinger, David, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H-Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Heid, Iris M., OʼConnell, Jeffrey R., Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Gonçalo R., Franke, Lude, Frayling, Timothy M., McCarthy, Mark I., Visscher, Peter M., Scherag, André, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Inês, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., and Speliotes, Elizabeth K.
- Published
- 2015
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61. Genetic contributions to stability and change in intelligence from childhood to old age
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Deary, Ian J., Yang, Jian, Davies, Gail, Harris, Sarah E., Tenesa, Albert, Liewald, David, Luciano, Michelle, Lopez, Lorna M., Gow, Alan J., Corley, Janie, Redmond, Paul, Fox, Helen C., Rowe, Suzanne J., Haggarty, Paul, McNeill, Geraldine, Goddard, Michael E., Porteous, David J., Whalley, Lawrence J., Starr, John M., and Visscher, Peter M.
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Intellect -- Genetic aspects -- Research ,Intelligence levels -- Genetic aspects -- Research ,Aging -- Research -- Genetic aspects ,Single nucleotide polymorphisms -- Research -- Genetic aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Understanding the determinants of healthy mental ageing is a priority for society today (1,2). So far, we know that intelligence differences show high stability from childhood to old age (3,4) and there are estimates of the genetic contribution to intelligence at different ages (5,6). However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative (7-10). Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years) (11,12). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals (13-17). We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change., General cognitive ability (also known as general intelligence, or g (18)) is an important human trait. It shows consistent and strong associations with important life outcomes such as educational and [...]
- Published
- 2012
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62. The Snake Bone Case: Law, Custom, and Justice in a Papua New Guinea Village Court
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Goddard, Michael
- Published
- 1996
63. Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture–prone atherosclerotic plaques.
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Edsfeldt, Andreas, Swart, Maarten, Singh, Pratibha, Dib, Lea, Sun, Jiangming, Cole, Jennifer E., Park, Inhye, Al-Sharify, Dania, Persson, Ana, Nitulescu, Mihaela, Borges, Patricia Das Neves, Kassiteridi, Christina, Goddard, Michael E., Lee, Regent, Volkov, Petr, Orho-Melander, Marju, Maegdefessel, Lars, Nilsson, Jan, Udalova, Irina, and Goncalves, Isabel
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ATHEROSCLEROTIC plaque ,INTERFERONS ,INTERFERON regulatory factors ,MACROPHAGES ,TRANSCRIPTION factors - Abstract
Aims Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. Methods and results Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE
−/− mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE−/− Irf5−/− mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. Conclusion Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture. [ABSTRACT FROM AUTHOR]- Published
- 2022
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64. William G. Hill (August 7, 1940 – December 17, 2021).
- Author
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Charlesworth, Brian and Goddard, Michael E.
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QUANTITATIVE genetics , *GENETIC drift , *HERITABILITY , *POPULATION genetics , *GENETIC models , *LIFE sciences , *INBREEDING , *ANIMAL breeding - Abstract
William G. Hill, universally known as Bill Hill, died on December 17, 2021, aged 81. Bill also compared the observed and predicted long-term response to selection and concluded that these data had little power to distinguish among different models for quantitative genetic variation, including the "infinitesimal model" that postulates a very large number of loci with very small effects (Hill 2010). Appropriately, John Sved and Bill wrote an insightful I Perspective i in Genetics reviewing 100 years of work on LD (Sved and Hill 2018). In particular, he was the first to quantify the role of new mutations in producing the variability needed for long-term continued responses to selection, which are such a remarkable feature of many artificial selection experiments and animal and plant breeding programs (Hill 1982a,b; Keightley and Hill 1983). [Extracted from the article]
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- 2022
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65. The number of loci that affect milk production traits in dairy cattle
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Chamberlain, Amanda Jane, McPartlan, Helen Clare, and Goddard, Michael Edward
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Dairy cattle -- Genetic aspects ,Dairy cattle -- Physiological aspects ,Milk production -- Genetic aspects ,Livestock productivity -- Physiological aspects ,Quantitative trait loci -- Measurement ,Quantitative trait loci -- Influence ,Biological sciences - Abstract
We have used the results of an experiment mapping quantitative trait loci (QTL) affecting milk yield and composition to estimate the total number of QTL affecting these traits. We did this by estimating the number of segregating QTL within a half-sib daughter design using logic similar to that used to estimate the 'false discovery rate' (FDR). In a half-sib daughter design with six sire families we estimate that the average sire was heterozygous for ~5 QTL per trait. Also, in most cases only one sire was heterozygous for any one QTL; therefore at least 30 QTL were likely to be segregating for these milk production traits in this Holstein population.
- Published
- 2007
66. Expressions of interest: informal usury in urban Papua New Guinea
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Goddard, Michael
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Papua New Guinea -- Economic aspects ,Usury -- Public opinion ,Usury laws -- Public opinion ,Regional focus/area studies - Abstract
This article examines the nature and practice of small scale usury in a 'grassroots' urban community in Port Moresby, Papua New Guinea. In this environment the moneylenders are people of limited financial resources, barely richer than their clients. The latter are often self-employed in informal occupations. Using examples from eases where usurers have taken defaulting debtors to urban 'village courts,' I show how debt is negotiated by usurers and clients, and I indicate differences between local attitudes toward usury and those that are generally held in Western societies. I discuss prevalent views in social science literature about the influence of kinship sensibilities on socioeconomic behavior in urban Papua New Guinea and attempt to situate moneylending for profit in Port Moresby in the complex local integration of the so-called gift economy and the cash economy.
- Published
- 2005
67. Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimerʼs disease, multiple sclerosis and endometriosis
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Lee, S. Hong, Harold, Denise, Nyholt, Dale R., Goddard, Michael E., Zondervan, Krina T., Williams, Julie, Montgomery, Grant W., Wray, Naomi R., and Visscher, Peter M.
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- 2013
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68. FTO genotype is associated with phenotypic variability of body mass index
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Yang, Jian, Loos, Ruth J. F., Powell, Joseph E., Medland, Sarah E., Speliotes, Elizabeth K., Chasman, Daniel I., Rose, Lynda M., Thorleifsson, Gudmar, Steinthorsdottir, Valgerdur, Mägi, Reedik, Waite, Lindsay, Vernon Smith, Albert, Yerges-Armstrong, Laura M., Monda, Keri L., Hadley, David, Mahajan, Anubha, Li, Guo, Kapur, Karen, Vitart, Veronique, Huffman, Jennifer E., Wang, Sophie R., Palmer, Cameron, Esko, Tõnu, Fischer, Krista, Hua Zhao, Jing, Demirkan, Ayşe, Isaacs, Aaron, Feitosa, Mary F., Luan, Jian’an, Heard-Costa, Nancy L., White, Charles, Jackson, Anne U., Preuss, Michael, Ziegler, Andreas, Eriksson, Joel, Kutalik, Zoltán, Frau, Francesca, Nolte, Ilja M., Van Vliet-Ostaptchouk, Jana V., Hottenga, Jouke-Jan, Jacobs, Kevin B., Verweij, Niek, Goel, Anuj, Medina-Gomez, Carolina, Estrada, Karol, Lynn Bragg-Gresham, Jennifer, Sanna, Serena, Sidore, Carlo, Tyrer, Jonathan, Teumer, Alexander, Prokopenko, Inga, Mangino, Massimo, Lindgren, Cecilia M., Assimes, Themistocles L., Shuldiner, Alan R., Hui, Jennie, Beilby, John P., McArdle, Wendy L., Hall, Per, Haritunians, Talin, Zgaga, Lina, Kolcic, Ivana, Polasek, Ozren, Zemunik, Tatijana, Oostra, Ben A., Juhani Junttila, M., Grönberg, Henrik, Schreiber, Stefan, Peters, Annette, Hicks, Andrew A., Stephens, Jonathan, Foad, Nicola S., Laitinen, Jaana, Pouta, Anneli, Kaakinen, Marika, Willemsen, Gonneke, Vink, Jacqueline M., Wild, Sarah H., Navis, Gerjan, Asselbergs, Folkert W., Homuth, Georg, John, Ulrich, Iribarren, Carlos, Harris, Tamara, Launer, Lenore, Gudnason, Vilmundur, O’Connell, Jeffrey R., Boerwinkle, Eric, Cadby, Gemma, Palmer, Lyle J., James, Alan L., Musk, Arthur W., Ingelsson, Erik, Psaty, Bruce M., Beckmann, Jacques S., Waeber, Gerard, Vollenweider, Peter, Hayward, Caroline, Wright, Alan F., Rudan, Igor, Groop, Leif C., Metspalu, Andres, Tee Khaw, Kay, van Duijn, Cornelia M., Borecki, Ingrid B., Province, Michael A., Wareham, Nicholas J., Tardif, Jean-Claude, Huikuri, Heikki V., Adrienne Cupples, L., Atwood, Larry D., Fox, Caroline S., Boehnke, Michael, Collins, Francis S., Mohlke, Karen L., Erdmann, Jeanette, Schunkert, Heribert, Hengstenberg, Christian, Stark, Klaus, Lorentzon, Mattias, Ohlsson, Claes, Cusi, Daniele, Staessen, Jan A., Van der Klauw, Melanie M., Pramstaller, Peter P., Kathiresan, Sekar, Jolley, Jennifer D., Ripatti, Samuli, Jarvelin, Marjo-Riitta, de Geus, Eco J. C., Boomsma, Dorret I., Penninx, Brenda, Wilson, James F., Campbell, Harry, Chanock, Stephen J., van der Harst, Pim, Hamsten, Anders, Watkins, Hugh, Hofman, Albert, Witteman, Jacqueline C., Uitterlinden, André G., Rivadeneira, Fernando, Zillikens, M. Carola, Kiemeney, Lambertus A., Vermeulen, Sita H., Abecasis, Goncalo R., Schlessinger, David, Schipf, Sabine, Stumvoll, Michael, Tönjes, Anke, Spector, Tim D., North, Kari E., Lettre, Guillaume, McCarthy, Mark I., Berndt, Sonja I., Heath, Andrew C., Madden, Pamela A. F., Nyholt, Dale R., Montgomery, Grant W., Martin, Nicholas G., McKnight, Barbara, Strachan, David P., Hill, William G., Snieder, Harold, Ridker, Paul M., Thorsteinsdottir, Unnur, Stefansson, Kari, Frayling, Timothy M., Hirschhorn, Joel N., Goddard, Michael E., and Visscher, Peter M.
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- 2012
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69. CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.
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Kassiteridi, Christina, Cole, Jennifer E., Griseri, Thibault, Falck-Hansen, Mika, Goddard, Michael E., Seneviratne, Anusha N., Green, Patricia A., Park, Inhye, Shami, Annelie G., Pattarabanjird, Tanyaporn, Upadhye, Aditi, Taylor, Angela M., Handa, Ashok, Channon, Keith M., Lutgens, Esther, McNamara, Coleen A., Williams, Richard O., and Monaco, Claudia
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- 2021
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70. Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues.
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Prowse-Wilkins, Claire P., Wang, Jianghui, Xiang, Ruidong, Garner, Josie B., Goddard, Michael E., and Chamberlain, Amanda J.
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MAMMARY glands ,GENETIC variation ,IMMUNOPRECIPITATION ,POST-translational modification ,BOS ,GENE expression ,PHENOTYPES - Abstract
Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.g., transcription factors) using a method called Chromatin immunoprecipitation followed by sequencing (ChIP-seq). In this study ChIP-seq was performed to find functional regions in the bovine genome by assaying for four histone modifications (H3K4Me1, H3K4Me3, H3K27ac, and H3K27Me3) and one transcription factor (CTCF) in 6 tissues (heart, kidney, liver, lung, mammary and spleen) from 2 to 3 lactating dairy cows. Eighty-six ChIP-seq samples were generated in this study, identifying millions of functional regions in the bovine genome. Combinations of histone modifications and CTCF were found using ChromHMM and annotated by comparing with active and inactive genes across the genome. Functional marks differed between tissues highlighting areas which might be particularly important to tissue-specific regulation. Supporting the cis-regulatory role of functional regions, the read counts in some ChIP peaks correlated with nearby gene expression. The functional regions identified in this study were enriched for putative causal variants as seen in other species. Interestingly, regions which correlated with gene expression were particularly enriched for potential causal variants. This supports the hypothesis that complex traits are regulated by variants that alter gene expression. This study provides one of the largest ChIP-seq annotation resources in cattle including, for the first time, in the mammary gland of lactating cows. By linking regulatory regions to expression QTL and trait QTL we demonstrate a new strategy for identifying causal variants in cattle. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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71. Bedlam in paradise: a critical history of psychiatry in Papua New Guinea
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Goddard, Michael
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Papuans -- Psychological aspects ,Psychiatry -- History ,Psychiatric services -- Papua New Guinea ,Papua New Guinea -- History - Published
- 1992
72. Genome position specific priors for genomic prediction
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Brøndum Rasmus, Su Guosheng, Lund Mogens, Bowman Philip J, Goddard Michael E, and Hayes Benjamin J
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Genomic prediction combined populations ,Genomic location ,Bayesian prediction ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The accuracy of genomic prediction is highly dependent on the size of the reference population. For small populations, including information from other populations could improve this accuracy. The usual strategy is to pool data from different populations; however, this has not proven as successful as hoped for with distantly related breeds. BayesRS is a novel approach to share information across populations for genomic predictions. The approach allows information to be captured even where the phase of SNP alleles and casuative mutation alleles are reversed across populations, or the actual casuative mutation is different between the populations but affects the same gene. Proportions of a four-distribution mixture for SNP effects in segments of fixed size along the genome are derived from one population and set as location specific prior proportions of distributions of SNP effects for the target population. The model was tested using dairy cattle populations of different breeds: 540 Australian Jersey bulls, 2297 Australian Holstein bulls and 5214 Nordic Holstein bulls. The traits studied were protein-, fat- and milk yield. Genotypic data was Illumina 777K SNPs, real or imputed. Results Results showed an increase in accuracy of up to 3.5% for the Jersey population when using BayesRS with a prior derived from Australian Holstein compared to a model without location specific priors. The increase in accuracy was however lower than was achieved when reference populations were combined to estimate SNP effects, except in the case of fat yield. The small size of the Jersey validation set meant that these improvements in accuracy were not significant using a Hotelling-Williams t-test at the 5% level. An increase in accuracy of 1-2% for all traits was observed in the Australian Holstein population when using a prior derived from the Nordic Holstein population compared to using no prior information. These improvements were significant (P Conclusion For some traits the method might be advantageous compared to pooling of reference data for distantly related populations, but further investigation is needed to confirm the results. For closely related populations the method does not perform better than pooling reference data. However, it does give an increased accuracy compared to analysis based on only one reference population, without an increased computational burden. The approach described here provides a general setup for inclusion of location specific priors: the approach could be used to include biological information in genomic predictions.
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- 2012
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73. The use of communal rearing of families and DNA pooling in aquaculture genomic selection schemes
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Meuwissen Theo HE, Sonesson Anna K, and Goddard Michael E
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Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract Background Traditional family-based aquaculture breeding programs, in which families are kept separately until individual tagging and most traits are measured on the sibs of the candidates, are costly and require a high level of reproductive control. The most widely used alternative is a selection scheme, where families are reared communally and the candidates are selected based on their own individual measurements of the traits under selection. However, in the latter selection schemes, inclusion of new traits depends on the availability of non-invasive techniques to measure the traits on selection candidates. This is a severe limitation of these schemes, especially for disease resistance and fillet quality traits. Methods Here, we present a new selection scheme, which was validated using computer simulations comprising 100 families, among which 1, 10 or 100 were reared communally in groups. Pooling of the DNA from 2000, 20000 or 50000 test individuals with the highest and lowest phenotypes was used to estimate 500, 5000 or 10000 marker effects. One thousand or 2000 out of 20000 candidates were preselected for a growth-like trait. These pre-selected candidates were genotyped, and they were selected on their genome-wide breeding values for a trait that could not be measured on the candidates. Results A high accuracy of selection, i.e. 0.60-0.88 was obtained with 20000-50000 test individuals but it was reduced when only 2000 test individuals were used. This shows the importance of having large numbers of phenotypic records to accurately estimate marker effects. The accuracy of selection decreased with increasing numbers of families per group. Conclusions This new selection scheme combines communal rearing of families, pre-selection of candidates, DNA pooling and genomic selection and makes multi-trait selection possible in aquaculture selection schemes without keeping families separately until individual tagging is possible. The new scheme can also be used for other farmed species, for which the cost of genotyping test individuals may be high, e.g. if trait heritability is low.
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- 2010
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74. Using the realized relationship matrix to disentangle confounding factors for the estimation of genetic variance components of complex traits
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Visscher Peter M, Goddard Michael E, Lee Sang, and van der Werf Julius HJ
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Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract Background In the analysis of complex traits, genetic effects can be confounded with non-genetic effects, especially when using full-sib families. Dominance and epistatic effects are typically confounded with additive genetic and non-genetic effects. This confounding may cause the estimated genetic variance components to be inaccurate and biased. Methods In this study, we constructed genetic covariance structures from whole-genome marker data, and thus used realized relationship matrices to estimate variance components in a heterogenous population of ~ 2200 mice for which four complex traits were investigated. These mice were genotyped for more than 10,000 single nucleotide polymorphisms (SNP) and the variances due to family, cage and genetic effects were estimated by models based on pedigree information only, aggregate SNP information, and model selection for specific SNP effects. Results and conclusions We show that the use of genome-wide SNP information can disentangle confounding factors to estimate genetic variances by separating genetic and non-genetic effects. The estimated variance components using realized relationship were more accurate and less biased, compared to those based on pedigree information only. Models that allow the selection of individual SNP in addition to fitting a relationship matrix are more efficient for traits with a significant dominance variance.
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- 2010
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75. Improving Genomic Prediction of Crossbred and Purebred Dairy Cattle.
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Khansefid, Majid, Goddard, Michael E., Haile-Mariam, Mekonnen, Konstantinov, Kon V., Schrooten, Chris, de Jong, Gerben, Jewell, Erica G., O'Connor, Erin, Pryce, Jennie E., Daetwyler, Hans D., and MacLeod, Iona M.
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CATTLE crossbreeding ,FORECASTING ,DAIRY cattle ,PREDICTION models - Abstract
This study assessed the accuracy and bias of genomic prediction (GP) in purebred Holstein (H) and Jersey (J) as well as crossbred (H and J) validation cows using different reference sets and prediction strategies. The reference sets were made up of different combinations of 36,695 H and J purebreds and crossbreds. Additionally, the effect of using different sets of marker genotypes on GP was studied (conventional panel: 50k, custom panel enriched with, or close to, causal mutations: XT_50k, and conventional high-density with a limited custom set: pruned HDnGBS). We also compared the use of genomic best linear unbiased prediction (GBLUP) and Bayesian (emBayesR) models, and the traits tested were milk, fat, and protein yields. On average, by including crossbred cows in the reference population, the prediction accuracies increased by 0.01–0.08 and were less biased (regression coefficient closer to 1 by 0.02–0.16), and the benefit was greater for crossbreds compared to purebreds. The accuracy of prediction increased by 0.02 using XT_50k compared to 50k genotypes without affecting the bias. Although using pruned HDnGBS instead of 50k also increased the prediction accuracy by about 0.02, it increased the bias for purebred predictions in emBayesR models. Generally, emBayesR outperformed GBLUP for prediction accuracy when using 50k or pruned HDnGBS genotypes, but the benefits diminished with XT_50k genotypes. Crossbred predictions derived from a joint pure H and J reference were similar in accuracy to crossbred predictions derived from the two separate purebred reference sets and combined proportional to breed composition. However, the latter approach was less biased by 0.13. Most interestingly, using an equalized breed reference instead of an H-dominated reference, on average, reduced the bias of prediction by 0.16–0.19 and increased the accuracy by 0.04 for crossbred and J cows, with a little change in the H accuracy. In conclusion, we observed improved genomic predictions for both crossbreds and purebreds by equalizing breed contributions in a mixed breed reference that included crossbred cows. Furthermore, we demonstrate, that compared to the conventional 50k or high-density panels, our customized set of 50k sequence markers improved or matched the prediction accuracy and reduced bias with both GBLUP and Bayesian models. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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76. Law and Order in a Weak State: Crime and Politics in Papua New Guinea. (Book Reviews)
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Goddard, Michael
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Law and Order in a Weak State: Crime and Politics in Papua New Guinea (Book) ,Books -- Book reviews - Abstract
Law and Order in a Weak State: Crime and Politics in Papua New Guinea, by Sinclair Dinnen. Pacific Islands Monograph Series 17. Honolulu: University of Hawai'i Press, 2001. ISBN 0-8248-2280-3; […]
- Published
- 2002
77. Encompassing Others: The Magic of Modernity in Melanesia
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Goddard, Michael
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Encompassing Others: The Magic of Modernity in Melanesia (Book) ,Books -- Book reviews ,Anthropology/archeology/folklore ,Regional focus/area studies - Published
- 2002
78. Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits.
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Ruidong Xiang, van den Berg, Irene, MacLeod, Iona M., Hayes, Benjamin J., Prowse-Wilkins, Claire P., Min Wang, Bolormaa, Sunduimijid, Zhiqian Liu, Rochfort, Simone J., Reich, Coralie M., Mason, Brett A., Jagt, Christy J. Vander, Daetwyler, Hans D., Lund, Mogens S., Chamberlain, Amanda J., and Goddard, Michael E.
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GENE expression ,GENETIC regulation ,HERITABILITY ,CATTLE ,COWS - Abstract
Many genome variants shaping mammalian phenotype are hypothesized to regulate gene transcription and/or to be under selection. However, most of the evidence to support this hypothesis comes from human studies. Systematic evidence for regulatory and evolutionary signals contributing to complex traits in a different mammalian model is needed. Sequence variants associated with gene expression (expression quantitative trait loci [eQTLs]) and concentration of metabolites (metabolic quantitative trait loci [mQTLs]) and under histone-modification marks in several tissues were discovered from multiomics data of over 400 cattle. Variants under selection and evolutionary constraint were identified using genome databases of multiple species. These analyses defined 30 sets of variants, and for each set, we estimated the genetic variance the set explained across 34 complex traits in 11,923 bulls and 32,347 cows with 17,669,372 imputed variants. The per-variant trait heritability of these sets across traits was highly consistent (r > 0.94) between bulls and cows. Based on the per-variant heritability, conserved sites across 100 vertebrate species and mQTLs ranked the highest, followed by eQTLs, young variants, those under histone-modification marks, and selection signatures. From these results,we defined a Functional-And-Evolutionary Trait Heritability (FAETH) score indicating the functionality and predicted heritability of each variant. In additional 7,551 cattle, the high FAETH-ranking variants had significantly increased genetic variances and genomic prediction accuracies in 3 production traits compared to the low FAETH-ranking variants. The FAETH framework combines the information of gene regulation, evolution, and trait heritability to rank variants, and the publicly available FAETH data provide a set of biological priors for cattle genomic selection worldwide. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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79. The Rascal Road: Crime, Prestige, and Development in Papua New Guinea
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Goddard, Michael
- Published
- 1995
80. Papua New Guinea's Last Place: Experiences of Constraint in a Postcolonial Prison
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Goddard, Michael
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Papua New Guinea's Last Place: Experiences of Constraint in a Postcolonial Prison (Book) -- Book reviews ,Books -- Book reviews ,Anthropology/archeology/folklore ,Regional focus/area studies - Published
- 2004
81. From R.A. Fisher's 1918 Paper to GWAS a Century Later.
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Visscher, Peter M. and Goddard, Michael E.
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- *
GENETICS -- History , *COMPARATIVE studies , *GENOMES , *HUMAN genome , *PERSONALITY - Abstract
The genetics and evolution of complex traits, including quantitative traits and disease, have been hotly debated ever since Darwin. A century ago, a paper from R.A. Fisher reconciled Mendelian and biometrical genetics in a landmark contribution that is now accepted as the main foundation stone of the field of quantitative genetics. Here, we give our perspective on Fisher's 1918 paper in the context of how and why it is relevant in today's genome era. We mostly focus on human trait variation, in part because Fisher did so too, but the conclusions are general and extend to other natural populations, and to populations undergoing artificial selection. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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82. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity.
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Cole, Jennifer E, Park, Inhye, Ahern, David J, Kassiteridi, Christina, Abeam, Dina Danso, Goddard, Michael E, Green, Patricia, Maffia, Pasquale, and Monaco, Claudia
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ATHEROSCLEROSIS ,CYTOMETRY ,MYELOID leukemia ,TIME-of-flight spectrometry ,LEUCOCYTES - Abstract
Aims Atherosclerosis is characterized by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Methods and results Apolipoprotein E-deficient (ApoE
−/− ) mice were fed a chow or a high fat (western) diet for 12 weeks. Single-cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE−/− mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell, and innate lymphoid cell (ILC) populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C− ), pDC, and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2. Conclusions A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE−/− mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire toward inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2018
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83. Meta-analysis of sequence-based association studies across three cattle breeds reveals 25 QTL for fat and protein percentages in milk at nucleotide resolution.
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Pausch, Hubert, Emmerling, Reiner, Gredler-Grandl, Birgit, Fries, Ruedi, Daetwyler, Hans D., and Goddard, Michael E.
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NUCLEOTIDES ,NUCLEIC acids ,DATA analysis ,CATTLE breeds ,LIVESTOCK breeds - Abstract
Background: Genotyping and whole-genome sequencing data have been generated for hundreds of thousands of cattle. International consortia used these data to compile imputation reference panels that facilitate the imputation of sequence variant genotypes for animals that have been genotyped using dense microarrays. Association studies with imputed sequence variant genotypes allow for the characterization of quantitative trait loci (QTL) at nucleotide resolution particularly when individuals from several breeds are included in the mapping populations. Results: We imputed genotypes for 28 million sequence variants in 17,229 cattle of the Braunvieh, Fleckvieh and Holstein breeds in order to compile large mapping populations that provide high power to identify QTL for milk production traits. Association tests between imputed sequence variant genotypes and fat and protein percentages in milk uncovered between six and thirteen QTL (P < 1e-8) per breed. Eight of the detected QTL were significant in more than one breed. We combined the results across breeds using meta-analysis and identified a total of 25 QTL including six that were not significant in the within-breed association studies. Two missense mutations in the ABCG2 (p.Y581S, rs43702337, P = 4.3e-34) and GHR (p.F279Y, rs385640152, P = 1.6e-74) genes were the top variants at QTL on chromosomes 6 and 20. Another known causal missense mutation in the DGAT1 gene (p.A232K, rs109326954, P = 8.4e-1436) was the second top variant at a QTL on chromosome 14 but its allelic substitution effects were inconsistent across breeds. It turned out that the conflicting allelic substitution effects resulted from flaws in the imputed genotypes due to the use of a multi-breed reference population for genotype imputation. Conclusions: Many QTL for milk production traits segregate across breeds and across-breed meta-analysis has greater power to detect such QTL than within-breed association testing. Association testing between imputed sequence variant genotypes and phenotypes of interest facilitates identifying causal mutations provided the accuracy of imputation is high. However, true causal mutations may remain undetected when the imputed sequence variant genotypes contain flaws. It is highly recommended to validate the effect of known causal variants in order to assess the ability to detect true causal mutations in association studies with imputed sequence variants. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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84. Urbanisation in the Island Pacific: Towards Sustainable Development
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Goddard, Michael
- Subjects
Urbanisation in the Island Pacific: Towards Sustainable Development (Book) -- Connell, John -- Lea, John ,Books -- Book reviews ,Anthropology/archeology/folklore - Abstract
Urbanisation in the Island Pacific: Towards sustainable development By John Connell and John Lea. London and New York: Routledge. 2002. Pp:xiv + 240. Price: 65 £ Analysing urbanisation across the [...]
- Published
- 2006
85. Application of a Bayesian non-linear model hybrid scheme to sequence data for genomic prediction and QTL mapping.
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Tingting Wang, Chen, Yi-Ping Phoebe, MacLeod, Iona M., Pryce, Jennie E., Goddard, Michael E., and Hayes, Ben J.
- Subjects
NUCLEOTIDE sequencing ,EXPECTATION-maximization algorithms ,MARKOV chain Monte Carlo ,CATTLE population genetics ,MILK yield ,CATTLE fertility - Abstract
Background: Using whole genome sequence data might improve genomic prediction accuracy, when compared with high-density SNP arrays, and could lead to identification of casual mutations affecting complex traits. For some traits, the most accurate genomic predictions are achieved with non-linear Bayesian methods. However, as the number of variants and the size of the reference population increase, the computational time required to implement these Bayesian methods (typically with Monte Carlo Markov Chain sampling) becomes unfeasibly long. Results: Here, we applied a new method, HyB_BR (for Hybrid BayesR), which implements a mixture model of normal distributions and hybridizes an Expectation-Maximization (EM) algorithm followed by Markov Chain Monte Carlo (MCMC) sampling, to genomic prediction in a large dairy cattle population with imputed whole genome sequence data. The imputed whole genome sequence data included 994,019 variant genotypes of 16,214 Holstein and Jersey bulls and cows. Traits included fat yield, milk volume, protein kg, fat% and protein% in milk, as well as fertility and heat tolerance. HyB_BR achieved genomic prediction accuracies as high as the full MCMC implementation of BayesR, both for predicting a validation set of Holstein and Jersey bulls (multi-breed prediction) and a validation set of Australian Red bulls (across-breed prediction). HyB_BR had a ten fold reduction in compute time, compared with the MCMC implementation of BayesR (48 hours versus 594 hours). We also demonstrate that in many cases HyB_BR identified sequence variants with a high posterior probability of affecting the milk production or fertility traits that were similar to those identified in BayesR. For heat tolerance, both HyB_BR and BayesR found variants in or close to promising candidate genes associated with this trait and not detected by previous studies. Conclusions: The results demonstrate that HyB_BR is a feasible method for simultaneous genomic prediction and QTL mapping with whole genome sequence in large reference populations. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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86. Multiple-trait QTL mapping and genomic prediction for wool traits in sheep.
- Author
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Bolormaa, Sunduimijid, Swan, Andrew A., Brown, Daniel J., Hatcher, Sue, Moghaddar, Nasir, van der Werf, Julius H., Goddard, Michael E., and Daetwyler, Hans D.
- Subjects
SHEEP genetics ,GENOMES ,SHEEP breeding - Abstract
Background: The application of genomic selection to sheep breeding could lead to substantial increases in profitability of wool production due to the availability of accurate breeding values from single nucleotide polymorphism (SNP) data. Several key traits determine the value of wool and influence a sheep's susceptibility to fleece rot and fly strike. Our aim was to predict genomic estimated breeding values (GEBV) and to compare three methods of combining information across traits to map polymorphisms that affect these traits. Methods: GEBV for 5726 Merino and Merino crossbred sheep were calculated using BayesR and genomic best linear unbiased prediction (GBLUP) with real and imputed 510,174 SNPs for 22 traits (at yearling and adult ages) including wool production and quality, and breech conformation traits that are associated with susceptibility to fly strike. Accuracies of these GEBV were assessed using fivefold cross-validation. We also devised and compared three approximate multi-trait analyses to map pleiotropic quantitative trait loci (QTL): a multi-trait genome-wide association study and two multi-trait methods that use the output from BayesR analyses. One BayesR method used local GEBV for each trait, while the other used the posterior probabilities that a SNP had an effect on each trait. Results: BayesR and GBLUP resulted in similar average GEBV accuracies across traits (~0.22). BayesR accuracies were highest for wool yield and fibre diameter (>0.40) and lowest for skin quality and dag score (<0.10). Generally, accuracy was higher for traits with larger reference populations and higher heritability. In total, the three multi-trait analyses identified 206 putative QTL, of which 20 were common to the three analyses. The two BayesR multi-trait approaches mapped QTL in a more defined manner than the multi-trait GWAS. We identified genes with known effects on hair growth (i.e. FGF5, STAT3, KRT86, and ALX4) near SNPs with pleiotropic effects on wool traits. Conclusions: The mean accuracy of genomic prediction across wool traits was around 0.22. The three multi-trait analyses identified 206 putative QTL across the ovine genome. Detailed phenotypic information helped to identify likely candidate genes. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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87. Evaluation of the accuracy of imputed sequence variant genotypes and their utility for causal variant detection in cattle.
- Author
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Pausch, Hubert, MacLeod, Iona M., Fries, Ruedi, Emmerling, Reiner, Bowman, Phil J., Daetwyler, Hans D., and Goddard, Michael E.
- Subjects
CATTLE locomotion ,ANIMAL locomotion ,GENOTYPES ,NUCLEOTIDE sequencing ,HEMOGLOBIN polymorphisms - Abstract
Background: The availability of dense genotypes and whole-genome sequence variants from various sources offers the opportunity to compile large datasets consisting of tens of thousands of individuals with genotypes at millions of polymorphic sites that may enhance the power of genomic analyses. The imputation of missing genotypes ensures that all individuals have genotypes for a shared set of variants. Results: We evaluated the accuracy of imputation from dense genotypes to whole-genome sequence variants in 249 Fleckvieh and 450 Holstein cattle using Minimac and FImpute. The sequence variants of a subset of the animals were reduced to the variants that were included on the Illumina BovineHD genotyping array and subsequently inferred in silico using either within- or multi-breed reference populations. The accuracy of imputation varied considerably across chromosomes and dropped at regions where the bovine genome contains segmental duplications. Depending on the imputation strategy, the correlation between imputed and true genotypes ranged from 0.898 to 0.952. The accuracy of imputation was higher with Minimac than FImpute particularly for variants with a low minor allele frequency. Using a multi-breed reference population increased the accuracy of imputation, particularly when FImpute was used to infer genotypes. When the sequence variants were imputed using Minimac, the true genotypes were more correlated to predicted allele dosages than best-guess genotypes. The computing costs to impute 23,256,743 sequence variants in 6958 animals were ten-fold higher with Minimac than FImpute. Association studies with imputed sequence variants revealed seven quantitative trait loci (QTL) for milk fat percentage. Two causal mutations in the DGAT1 and GHR genes were the most significantly associated variants at two QTL on chromosomes 14 and 20 when Minimac was used to infer genotypes. Conclusions: The population-based imputation of millions of sequence variants in large cohorts is computationally feasible and provides accurate genotypes. However, the accuracy of imputation is low in regions where the genome contains large segmental duplications or the coverage with array-derived single nucleotide polymorphisms is poor. Using a reference population that includes individuals from many breeds increases the accuracy of imputation particularly at low-frequency variants. Considering allele dosages rather than best-guess genotypes as explanatory variables is advantageous to detect causal mutations in association studies with imputed sequence variants. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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88. A hybrid expectation maximisation and MCMC sampling algorithm to implement Bayesian mixture model based genomic prediction and QTL mapping.
- Author
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Wang, Tingting, Chen, Yi-Ping Phoebe, Bowman, Phil J., Goddard, Michael E., and Hayes, Ben J.
- Subjects
GENOMICS ,GENE mapping ,MARKOV chain Monte Carlo ,PREDICTION models ,EXPECTATION-maximization algorithms - Abstract
Background: Bayesian mixture models in which the effects of SNP are assumed to come from normal distributions with different variances are attractive for simultaneous genomic prediction and QTL mapping. These models are usually implemented with Monte Carlo Markov Chain (MCMC) sampling, which requires long compute times with large genomic data sets. Here, we present an efficient approach (termed HyB_BR), which is a hybrid of an Expectation-Maximisation algorithm, followed by a limited number of MCMC without the requirement for burn-in. Results: To test prediction accuracy from HyB_BR, dairy cattle and human disease trait data were used. In the dairy cattle data, there were four quantitative traits (milk volume, protein kg, fat% in milk and fertility) measured in 16,214 cattle from two breeds genotyped for 632,002 SNPs. Validation of genomic predictions was in a subset of cattle either from the reference set or in animals from a third breeds that were not in the reference set. In all cases, HyB_BR gave almost identical accuracies to Bayesian mixture models implemented with full MCMC, however computational time was reduced by up to 1/17 of that required by full MCMC. The SNPs with high posterior probability of a non-zero effect were also very similar between full MCMC and HyB_BR, with several known genes affecting milk production in this category, as well as some novel genes. HyB_BR was also applied to seven human diseases with 4890 individuals genotyped for around 300 K SNPs in a case/control design, from the Welcome Trust Case Control Consortium (WTCCC). In this data set, the results demonstrated again that HyB_BR performed as well as Bayesian mixture models with full MCMC for genomic predictions and genetic architecture inference while reducing the computational time from 45 h with full MCMC to 3 h with HyB_BR. Conclusions: The results for quantitative traits in cattle and disease in humans demonstrate that HyB_BR can perform equally well as Bayesian mixture models implemented with full MCMC in terms of prediction accuracy, but with up to 17 times faster than the full MCMC implementations. The HyB_BR algorithm makes simultaneous genomic prediction, QTL mapping and inference of genetic architecture feasible in large genomic data sets. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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89. Inflammatory-Related Genetic Variants in Non-Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment.
- Author
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Masson-Lecomte, Alexandra, de Maturana, Evangelina López, Goddard, Michael E., Picornell, Antoni, Rava, Marta, González-Neira, Anna, Márquez, Mirari, Carrato, Alfredo, Tardon, Adonina, Lloreta, Josep, Garcia-Closas, Montserrat, Silverman, Debra, Rothman, Nathaniel, Kogevinas, Manolis, Allory, Yves, Chanock, Stephen J., Real, Francisco X., and Malats, Núria
- Abstract
Background: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammationrelated genes with non-muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression. Methods: We considered 822 NMIBC included in the SBC/ EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures. Results: While no SNP was found to be associated with risk-ofrecurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of-progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 × 10
-5 ) and two SNPs in MASP1 and AIRE, showed a posterior probability ≥80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively. Conclusions: Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC. Impact: This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases. [ABSTRACT FROM AUTHOR]- Published
- 2016
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90. Copy number variants in the sheep genome detected using multiple approaches.
- Author
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Jenkins, Gemma M., Goddard, Michael E., Black, Michael A., Brauning, Rudiger, Auvray, Benoit, Dodds, Ken G., Kijas, James W., Cockett, Noelle, and McEwan, John C.
- Subjects
- *
DNA copy number variations , *SHEEP genetics , *POLYMORPHISM (Zoology) , *NUCLEOTIDE sequencing , *GENOMICS - Abstract
Background: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. Results: In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). Conclusions: This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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91. Detailed phenotyping identifies genes with pleiotropic effects on body composition.
- Author
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Bolormaa, Sunduimijid, Hayes, Ben J., van der Werf, Julius H. J., Pethick, David, Goddard, Michael E., and Daetwyler, Hans D.
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BODY composition ,HUMAN genetic variation ,GENETIC pleiotropy ,GLYCOGEN synthases ,PHENOTYPES - Abstract
Background: Genetic variation in both the composition and distribution of fat and muscle in the body is important to human health as well as the healthiness and value of meat from cattle and sheep. Here we use detailed phenotyping and a multi-trait approach to identify genes explaining variation in body composition traits. Results: A multi-trait genome wide association analysis of 56 carcass composition traits measured on 10,613 sheep with imputed and real genotypes on 510,174 SNPs was performed. We clustered 71 significant SNPs into five groups based on their pleiotropic effects across the 56 traits. Among these 71 significant SNPs, one group of 11 SNPs affected the fatty acid profile of themuscle and were close to 8 genes involved in fatty acid or triglyceride synthesis. Another group of 23 SNPs had an effect on mature size, based on their pattern of effects across traits, but the genes near this group of SNPs did not share any obvious function. Many of the likely candidate genes near SNPs with significant pleiotropic effects on the 56 traits are involved in intra-cellular signalling pathways. Among the significant SNPs were some with a convincing candidate gene due to the function of the gene (e.g. glycogen synthase affecting glycogen concentration) or because the same gene was associated with similar traits in other species. Conclusions: Using a multi-trait analysis increased the power to detect associations between SNP and body composition traits compared with the single trait analyses. Detailed phenotypic information helped to identify a convincing candidate in some cases as did information from other species. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
92. Rare Variants in Transcript and Potential Regulatory Regions Explain a Small Percentage of the Missing Heritability of Complex Traits in Cattle.
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Gonzalez-Recio, Oscar, Daetwyler, Hans D., MacLeod, Iona M., Pryce, Jennie E., Bowman, Phil J., Hayes, Ben J., and Goddard, Michael E.
- Subjects
CATTLE diseases ,SINGLE nucleotide polymorphisms ,MILK yield ,HERITABILITY ,ESTIMATION theory - Abstract
The proportion of genetic variation in complex traits explained by rare variants is a key question for genomic prediction, and for identifying the basis of “missing heritability”–the proportion of additive genetic variation not captured by common variants on SNP arrays. Sequence variants in transcript and regulatory regions from 429 sequenced animals were used to impute high density SNP genotypes of 3311 Holstein sires to sequence. There were 675,062 common variants (MAF>0.05), 102,549 uncommon variants (0.01
- Published
- 2015
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93. Extensive variation between tissues in allele specific expression in an outbred mammal.
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Chamberlain, Amanda J., Vander Jagt, Christy J., Hayes, Benjamin J., Khansefid, Majid, Marett, Leah C., Millen, Catriona A., Nguyen, Thuy T. T., and Goddard, Michael E.
- Subjects
GENE expression in mammals ,ALLELES ,CHROMOSOMES ,RNA sequencing ,NUCLEOTIDE sequencing ,GENES - Abstract
Background: Allele specific gene expression (ASE), with the paternal allele more expressed than the maternal allele or vice versa, appears to be a common phenomenon in humans and mice. In other species the extent of ASE is unknown, and even in humans and mice there are several outstanding questions. These include; to what extent is ASE tissue specific? how often does the direction of allele expression imbalance reverse between tissues? how often is only one of the two alleles expressed? is there a genome wide bias towards expression of the paternal or maternal allele; and finally do genes that are nearby on a chromosome share the same direction of ASE? Here we use gene expression data (RNASeq) from 18 tissues from a single cow to investigate each of these questions in turn, and then validate some of these findings in two tissues from 20 cows. Results: Between 40 and 100 million sequence reads were generated per tissue across three replicate samples for each of the eighteen tissues from the single cow (the discovery dataset). A bovine gene expression atlas was created (the first from RNASeq data), and differentially expressed genes in each tissue were identified. To analyse ASE, we had access to unambiguously phased genotypes for all heterozygous variants in the cow's whole genome sequence, where these variants were homozygous in the whole genome sequence of her sire, and as a result we were able to map reads to parental genomes, to determine SNP and genes showing ASE in each tissue. In total 25,251 heterozygous SNP within 7985 genes were tested for ASE in at least one tissue. ASE was pervasive, 89 % of genes tested had significant ASE in at least one tissue. This large proportion of genes displaying ASE was confirmed in the two tissues in a validation dataset. For individual tissues the proportion of genes showing significant ASE varied from as low as 8-16 % of those tested in thymus to as high as 71-82 % of those tested in lung. There were a number of cases where the direction of allele expression imbalance reversed between tissues. For example the gene SPTY2D1 showed almost complete paternal allele expression in kidney and thymus, and almost complete maternal allele expression in the brain caudal lobe and brain cerebellum. Mono allelic expression (MAE) was common, with 1349 of 4856 genes (28 %) tested with more than one heterozygous SNP showing MAE. Across all tissues, 54.17 % of all genes with ASE favoured the paternal allele. Genes that are closely linked on the chromosome were more likely to show higher expression of the same allele (paternal or maternal) than expected by chance. We identified several long runs of neighbouring genes that showed either paternal or maternal ASE, one example was five adjacent genes (GIMAP8, GIMAP7 copy1, GIMAP4, GIMAP7 copy 2 and GIMAP5) that showed almost exclusive paternal expression in brain caudal lobe. Conclusions: Investigating the extent of ASE across 18 bovine tissues in one cow and two tissues in 20 cows demonstrated 1) ASE is pervasive in cattle, 2) the ASE is often MAE but ranges from MAE to slight overexpression of the major allele, 3) the ASE is most often tissue specific and that more than half the time displays divergent allele specific expression patterns across tissues, 4) across all genes there is a slight bias towards expression of the paternal allele and 5) genes expressing the same parental allele are clustered together more than expected by chance, and there are several runs of large numbers of genes expressing the same parental allele. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
94. Impact of QTL properties on the accuracy of multi-breed genomic prediction.
- Author
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Wientjes, Yvonne C. J., Calus, Mario P. L., Goddard, Michael E., and Hayes, Ben J.
- Subjects
GENOMES ,GENETIC algorithms ,FORECASTING ,GENETICS ,ANIMAL genetics - Abstract
Background: Although simulation studies show that combining multiple breeds in one reference population increases accuracy of genomic prediction, this is not always confirmed in empirical studies. This discrepancy might be due to the assumptions on quantitative trait loci (QTL) properties applied in simulation studies, including number of QTL, spectrum of QTL allele frequencies across breeds, and distribution of allele substitution effects. We investigated the effects of QTL properties and of including a random across- and within-breed animal effect in a genomic best linear unbiased prediction (GBLUP) model on accuracy of multi-breed genomic prediction using genotypes of Holstein-Friesian and Jersey cows. Methods: Genotypes of three classes of variants obtained from whole-genome sequence data, with moderately low, very low or extremely low average minor allele frequencies (MAF), were imputed in 3000 Holstein-Friesian and 3000 Jersey cows that had real high-density genotypes. Phenotypes of traits controlled by QTL with different properties were simulated by sampling 100 or 1000 QTL from one class of variants and their allele substitution effects either randomly from a gamma distribution, or computed such that each QTL explained the same variance, i.e. rare alleles had a large effect. Genomic breeding values for 1000 selection candidates per breed were estimated using GBLUP models including a random across- and a within-breed animal effect. Results: For all three classes of QTL allele frequency spectra, accuracies of genomic prediction were not affected by the addition of 2000 individuals of the other breed to a reference population of the same breed as the selection candidates. Accuracies of both single- and multi-breed genomic prediction decreased as MAF of QTL decreased, especially when rare alleles had a large effect. Accuracies of genomic prediction were similar for the models with and without a random within-breed animal effect, probably because of insufficient power to separate across- and within-breed animal effects. Conclusions: Accuracy of both single- and multi-breed genomic prediction depends on the properties of the QTL that underlie the trait. As QTL MAF decreased, accuracy decreased, especially when rare alleles had a large effect. This demonstrates that QTL properties are key parameters that determine the accuracy of genomic prediction. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
95. A computationally efficient algorithm for genomic prediction using a Bayesian model.
- Author
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Tingting Wang, Yi-Ping Phoebe Chen, Goddard, Michael E., Meuwissen, Theo H. E., Kemper, Kathryn E., and Hayes, Ben J.
- Subjects
GENETICS ,GENOTYPES ,MARKOV processes ,DAIRY cattle ,BLOOD proteins ,INBREEDING ,CATTLE - Abstract
Background: Genomic prediction of breeding values from dense single nucleotide polymorphisms (SNP) genotypes is used for livestock and crop breeding, and can also be used to predict disease risk in humans. For some traits, the most accurate genomic predictions are achieved with non-linear estimates of SNP effects from Bayesian methods that treat SNP effects as random effects from a heavy tailed prior distribution. These Bayesian methods are usually implemented via Markov chain Monte Carlo (MCMC) schemes to sample from the posterior distribution of SNP effects, which is computationally expensive. Our aim was to develop an efficient expectation-maximisation algorithm (emBayesR) that gives similar estimates of SNP effects and accuracies of genomic prediction than the MCMC implementation of BayesR (a Bayesian method for genomic prediction), but with greatly reduced computation time. Methods: emBayesR is an approximate EM algorithm that retains the BayesR model assumption with SNP effects sampled from a mixture of normal distributions with increasing variance. emBayesR differs from other proposed non-MCMC implementations of Bayesian methods for genomic prediction in that it estimates the effect of each SNP while allowing for the error associated with estimation of all other SNP effects. emBayesR was compared to BayesR using simulated data, and real dairy cattle data with 632 003 SNPs genotyped, to determine if the MCMC and the expectation-maximisation approaches give similar accuracies of genomic prediction. Results: We were able to demonstrate that allowing for the error associated with estimation of other SNP effects when estimating the effect of each SNP in emBayesR improved the accuracy of genomic prediction over emBayesR without including this error correction, with both simulated and real data. When averaged over nine dairy traits, the accuracy of genomic prediction with emBayesR was only 0.5% lower than that from BayesR. However, emBayesR reduced computing time up to 8-fold compared to BayesR. Conclusions: The emBayesR algorithm described here achieved similar accuracies of genomic prediction to BayesR for a range of simulated and real 630 K dairy SNP data. emBayesR needs less computing time than BayesR, which will allow it to be applied to larger datasets. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
96. Non-additive genetic variation in growth, carcass and fertility traits of beef cattle.
- Author
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Bolormaa, Sunduimijid, Pryce, Jennie E., Yuandan Zhang, Reverter, Antonio, Barendse, William, Hayes, Ben J., and Goddard, Michael E.
- Subjects
CATTLE genetics ,BEEF cattle ,GENE expression ,SINGLE nucleotide polymorphisms ,EPISTASIS (Genetics) ,CATTLE - Abstract
Background: A better understanding of non-additive variance could lead to increased knowledge on the genetic control and physiology of quantitative traits, and to improved prediction of the genetic value and phenotype of individuals. Genome-wide panels of single nucleotide polymorphisms (SNPs) have been mainly used to map additive effects for quantitative traits, but they can also be used to investigate non-additive effects. We estimated dominance and epistatic effects of SNPs on various traits in beef cattle and the variance explained by dominance, and quantified the increase in accuracy of phenotype prediction by including dominance deviations in its estimation. Methods: Genotype data (729 068 real or imputed SNPs) and phenotypes on up to 16 traits of 10 191 individuals from Bos taurus, Bos indicus and composite breeds were used. A genome-wide association study was performed by fitting the additive and dominance effects of single SNPs. The dominance variance was estimated by fitting a dominance relationship matrix constructed from the 729 068 SNPs. The accuracy of predicted phenotypic values was evaluated by best linear unbiased prediction using the additive and dominance relationship matrices. Epistatic interactions (additive × additive) were tested between each of the 28 SNPs that are known to have additive effects on multiple traits, and each of the other remaining 729 067 SNPs. Results: The number of significant dominance effects was greater than expected by chance and most of them were in the direction that is presumed to increase fitness and in the opposite direction to inbreeding depression. Estimates of dominance variance explained by SNPs varied widely between traits, but had large standard errors. The median dominance variance across the 16 traits was equal to 5% of the phenotypic variance. Including a dominance deviation in the prediction did not significantly increase its accuracy for any of the phenotypes. The number of additive × additive epistatic effects that were statistically significant was greater than expected by chance. Conclusions: Significant dominance and epistatic effects occur for growth, carcass and fertility traits in beef cattle but they are difficult to estimate precisely and including them in phenotype prediction does not increase its accuracy. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
97. Improved precision of QTL mapping using a nonlinear Bayesian method in a multi-breed population leads to greater accuracy of across-breed genomic predictions.
- Author
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Kemper, Kathryn E., Reich, Coralie M., Bowman, Philip J., vander Jagt, Christy J., Chamberlain, Amanda J., Mason, Brett A., Hayes, Benjamin J., and Goddard, Michael E.
- Subjects
DAIRY cattle genetics ,BAYESIAN analysis ,GENOMICS ,SINGLE nucleotide polymorphisms ,DAIRY cattle breeding ,ANIMAL population density ,GENE expression ,CATTLE - Abstract
Background: Genomic selection is increasingly widely practised, particularly in dairy cattle. However, the accuracy of current predictions using GBLUP (genomic best linear unbiased prediction) decays rapidly across generations, and also as selection candidates become less related to the reference population. This is likely caused by the effects of causative mutations being dispersed across many SNPs (single nucleotide polymorphisms) that span large genomic intervals. In this paper, we hypothesise that the use of a nonlinear method (BayesR), combined with a multi-breed (Holstein/Jersey) reference population will map causative mutations with more precision than GBLUP and this, in turn, will increase the accuracy of genomic predictions for selection candidates that are less related to the reference animals. Results: BayesR improved the across-breed prediction accuracy for Australian Red dairy cattle for five milk yield and composition traits by an average of 7% over the GBLUP approach (Australian Red animals were not included in the reference population). Using the multi-breed reference population with BayesR improved accuracy of prediction in Australian Red cattle by 2 - 5% compared to using BayesR with a single breed reference population. Inclusion of 8478 Holstein and 3917 Jersey cows in the reference population improved accuracy of predictions for these breeds by 4 and 5%. However, predictions for Holstein and Jersey cattle were similar using within-breed and multi-breed reference populations. We propose that the improvement in across-breed prediction achieved by BayesR with the multi-breed reference population is due to more precise mapping of quantitative trait loci (QTL), which was demonstrated for several regions. New candidate genes with functional links to milk synthesis were identified using differential gene expression in the mammary gland. Conclusions: QTL detection and genomic prediction are usually considered independently but persistence of genomic prediction accuracies across breeds requires accurate estimation of QTL effects. We show that accuracy of across-breed genomic predictions was higher with BayesR than with GBLUP and that BayesR mapped QTL more precisely. Further improvements of across-breed accuracy of genomic predictions and QTL mapping could be achieved by increasing the size of the reference population, including more breeds, and possibly by exploiting pleiotropic effects to improve mapping efficiency for QTL with small effects. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
98. Simultaneous Discovery, Estimation and Prediction Analysis of Complex Traits Using a Bayesian Mixture Model.
- Author
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Moser, Gerhard, Lee, Sang Hong, Hayes, Ben J., Goddard, Michael E., Wray, Naomi R., and Visscher, Peter M.
- Subjects
BAYESIAN analysis ,HERITABILITY ,MEDICAL genetics ,GENETICS of bipolar disorder ,MONOGENIC & polygenic inheritance (Genetics) ,GENETICS of type 2 diabetes ,GENETICS of rheumatoid arthritis - Abstract
Gene discovery, estimation of heritability captured by SNP arrays, inference on genetic architecture and prediction analyses of complex traits are usually performed using different statistical models and methods, leading to inefficiency and loss of power. Here we use a Bayesian mixture model that simultaneously allows variant discovery, estimation of genetic variance explained by all variants and prediction of unobserved phenotypes in new samples. We apply the method to simulated data of quantitative traits and Welcome Trust Case Control Consortium (WTCCC) data on disease and show that it provides accurate estimates of SNP-based heritability, produces unbiased estimators of risk in new samples, and that it can estimate genetic architecture by partitioning variation across hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633 to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases. The majority of those SNPs (>96%) had small effects, confirming a substantial polygenic component to common diseases. The proportion of the SNP-based variance explained by large effects (each SNP explaining 1% of the variance) varied markedly between diseases, ranging from almost zero for bipolar disorder to 72% for type 1 diabetes. Prediction analyses demonstrate that for diseases with major loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods outperform profile scoring or mixed model approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
99. A General Unified Framework to Assess the Sampling Variance of Heritability Estimates Using Pedigree or Marker-Based Relationships.
- Author
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Visscher, Peter M. and Goddard, Michael E.
- Subjects
- *
BIOMARKERS , *HERITABILITY , *GENETICS , *ANIMAL genetics , *ANIMAL breeding - Abstract
Heritability is a population parameter of importance in evolution, plant and animal breeding, and human medical genetics. It can be estimated using pedigree designs and, more recently, using relationships estimated from markers. We derive the sampling variance of the estimate of heritability for a wide range of experimental designs, assuming that estimation is by maximum likelihood and that the resemblance between relatives is solely due to additive genetic variation. We show that well-known results for balanced designs are special cases of a more general unified framework. For pedigree designs, the sampling variance is inversely proportional to the variance of relationship in the pedigree and it is proportional to 1/N, whereas for population samples it is approximately proportional to 1/N², where N is the sample size. Variation in relatedness is a key parameter in the quantification of the sampling variance of heritability. Consequently, the sampling variance is high for populations with large recent effective population size (e.g., humans) because this causes low variation in relationship. However, even using human population samples, low sampling variance is possible with high N. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
100. The Genetic Architecture of Climatic Adaptation of Tropical Cattle.
- Author
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Porto-Neto, Laercio R., Reverter, Antonio, Prayaga, Kishore C., Chan, Eva K. F., Johnston, David J., Hawken, Rachel J., Fordyce, Geoffry, Garcia, Jose Fernando, Sonstegard, Tad S., Bolormaa, Sunduimijid, Goddard, Michael E., Burrow, Heather M., Henshall, John M., Lehnert, Sigrid A., and Barendse, William
- Subjects
BIOLOGICAL adaptation ,BOOPHILUS microplus ,COMPUTATIONAL biology ,ANIMAL genetics ,VETERINARY medicine ,HAPLOTYPES - Abstract
Adaptation of global food systems to climate change is essential to feed the world. Tropical cattle production, a mainstay of profitability for farmers in the developing world, is dominated by heat, lack of water, poor quality feedstuffs, parasites, and tropical diseases. In these systems European cattle suffer significant stock loss, and the cross breeding of taurine x indicine cattle is unpredictable due to the dilution of adaptation to heat and tropical diseases. We explored the genetic architecture of ten traits of tropical cattle production using genome wide association studies of 4,662 animals varying from 0% to 100% indicine. We show that nine of the ten have genetic architectures that include genes of major effect, and in one case, a single location that accounted for more than 71% of the genetic variation. One genetic region in particular had effects on parasite resistance, yearling weight, body condition score, coat colour and penile sheath score. This region, extending 20 Mb on BTA5, appeared to be under genetic selection possibly through maintenance of haplotypes by breeders. We found that the amount of genetic variation and the genetic correlations between traits did not depend upon the degree of indicine content in the animals. Climate change is expected to expand some conditions of the tropics to more temperate environments, which may impact negatively on global livestock health and production. Our results point to several important genes that have large effects on adaptation that could be introduced into more temperate cattle without detrimental effects on productivity. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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