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Prospects and challenges for the conservation of farm animal genomic resources, 2015-2025

Bruford, Michael W.,Ginja, Catarina,Hoffmann, Irene,Joost, Stephane,Orozco-terWengel, Pablo,Alberto, Florian J.,Amaral, Andreia J.,Barbato, Mario,Biscarini, Filippo,Colli, Licia,Costa, Mafalda,Curik, Ino,Duruz, Solange,Ferencakovic, Maja,Fischer, Daniel,

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HYPOTHESIS AND THEORY published: 21 Oc obe 2015 doi: 10.3389/ gene.2015.00314 F on ie s in Gene ics | www. on ie sin.o g 1Oc obe 2015 | Volume 6 | A icle 314 Edi ed by: Pe e Do c, Uni e si y o Ljubljana, Slo enia Re iewed by: Juan S eibel, Michigan S a e Uni e si y, USA John B. Cole, Uni ed S a es Depa men o Ag icul u e, USA *Co espondence: Michael W. B u o d [email p o ec ed] Special y sec ion: This a icle was submi ed o Li es ock Genomics, a sec ion o he jou nal F on ie s in Gene ics Recei ed: 26 May 2015 Accep ed: 05 Oc obe 2015 Published: 21 Oc obe 2015 P ospec s and challenges o he conse a ion o a m animal genomic esou ces, 2015-2025 Michael W. B u o d1, 2*, Ca a ina Ginja3, 4, I ene Ho mann5, S éphane Joos 6, Pablo O ozco- e Wengel1, Flo ian J. Albe o7, And eia J. Ama al8, Ma io Ba ba o1, Filippo Bisca ini9, Licia Colli10, Ma alda Cos a1, Ino Cu ik11, Solange Du uz6, Maja Fe enˇ cako i´ c11, Daniel Fische 12, Robe Fi ak13, Linn F. G oene eld14, S ephen J. G. Hall15, Oli ie Hano e16, Faiz-ul Hassan16, 17, Philippe Helsen18, Lau a Iacolina19, Juha Kan anen12, 20, Ke in Leempoel6, Johannes A. Lens a21, Paolo Ajmone-Ma san10, Cha les Masembe22, Hend ik-Jan Megens23, Ma a Miele24, Ma kus Neudi schko25, Ezequiel L. Nicolazzi9, F ançois Pompanon7, Ju a Roosen26, Na alia Se ane27, Anama ija Sme ko28, Anama ia Š ambuk29, Ian S ee e 30, Syl ie S ucki6, China Supako n16, 31, Luis Telo Da Gama32, Michèle Tixie -Boicha d33, Daniel Wegmann34 and Xiangjiang Zhan35, 36 1School o Biosciences, Ca di Uni e si y, Ca di , UK, 2Sus ainable Places Resea ch Ins i u e, Ca di Uni e si y, Ca di , UK, 3Faculdade de Ciências, Cen o de Ecologia, E olução e Al e ações Ambien ais (CE3C), Uni e sidade de Lisboa, Lisboa, Po ugal, 4Cen o de In es igação em Biodi e sidade e Recu sos Gené icos (CIBIO-InBIO), Uni e sidade do Po o, Campus Ag á io de Vai ão, Po ugal, 5Food and Ag icul u e O ganiza ion o he Uni ed Na ions, Animal Gene ic Resou ces B anch, Animal P oduc ion and Heal h Di ision, Rome, I aly, 6Labo a o y o Geog aphic In o ma ion Sys ems (LASIG), School o Ci il and En i onmen al Enginee ing (ENAC), Ecole Poly echnique Fédé ale de Lausanne, Lausanne, Swi ze land, 7Labo a oi e d’Ecologie Alpine, Uni e si é G enoble Alpes, G enoble, F ance, 8Facul y o Sciences, BioISI- Biosys ems and In eg a i e Sciences Ins i u e, Uni e si y o Lisbon, Campo G ande, Po ugal, 9Pa co Tecnologico Padano, Lodi, I aly, 10 BioDNA Cen o di Rice ca sulla Biodi e si à a sul DNA An ico, Is i u o di Zoo ecnica, Uni e si à Ca olica del Sac o Cuo e di Piacenza, I aly, 11 Facul y o Ag icul u e, Uni e si y o Zag eb, Zag eb, C oa ia, 12 Na u al Resou ces Ins i u e Finland (Luke), G een Technology, Jokioinen, Finland, 13 Ins i u ü Popula ionsgene ik, Ve meduni, Vienna, Aus ia, 14 No dGen -The No dic Gene ic Resou ce Cen e , Ås, No way, 15 Li es ock Di e si y L d., Lincoln, UK, 16 School o Li e Sciences, Uni e si y o No ingham, No ingham, UK, 17 Depa men o Animal B eeding and Gene ics, Uni e si y o Ag icul u e, Faisalabad, Pakis an, 18 Cen e o Resea ch and Conse a ion, Royal Zoological Socie y o An we p, An we p, Belgium, 19 Depa men o Chemis y and Bioscience, Aalbo g Uni e si y, Aalbo g, Denma k, 20 Depa men o Biology, Uni e si y o Eas e n Finland, Kuopio, Finland, 21 Facul y o Ve e ina y Medicine, U ech Uni e si y, U ech , Ne he land, 22 Ins i u e o he En i onmen and Na u al Resou ces, Make e e Uni e si y, Kampala, Uganda, 23 Animal B eeding and Genomics Cen e, Wageningen Uni e si y, Wageningen, Ne he lands, 24 School o Planning and Geog aphy, Ca di Uni e si y, Ca di , UK, 25 Ag oscope, Swiss Na ional S ud Fa m, A enches, Swi ze land, 26 TUM School o Managemen , Technische Uni e si ä München, Munich, Ge many, 27 Depa men o Animal P oduc ion, Ve e ina y Facul y, Uni e sidad Complu ense de Mad id, Mad id, Spain, 28 C oa ian Ag icul u al Agency, Zag eb, C oa ia, 29 Depa men o Biology, Facul y o Science, Uni e si y o Zag eb, Zag eb, C oa ia, 30 Eu opean Molecula Biology Labo a o y, Eu opean Bioin o ma ics Ins i u e, Wellcome T us Genome Campus, Hinx on, Camb idge, UK, 31 School o Ag icul u al Technology, Walailak Uni e si y, Tha Sala, Thailand, 32 Cen e o Resea ch in Animal Heal h (CIISA) – Facul y o Ve e ina y Medicine, Uni e si y o Lisbon, Lisbon, Po ugal, 33 INRA, Ag oPa isTech, UMR GABI, Jouy-en-Josas, F ance, 34 Depa men o Biology, Uni e si y o F ibou g, F ibou g, Swi ze land, 35 Key Labo a o y o Animal Ecology and Conse a ion Biology, Ins i u e o Zoology, Chinese Academy o Sciences, Beijing, China, 36 Ca di Uni e si y – Ins i u e o Zoology, Join Labo a o y o Biocomplexi y Resea ch, Beijing, China Li es ock conse a ion p ac ice is changing apidly in ligh o policy de elopmen s, clima e change and di e si ying ma ke demands. The las decade has seen a s ep change in echnology and analy ical app oaches a ailable o de ine, manage and conse e Fa m Animal Genomic Resou ces (FAnGR). Howe e , hese apid changes pose challenges o FAnGR conse a ion in e ms o echnological con inui y, analy ical capaci y and in eg a i e me hodologies needed o ully exploi new, mul idimensional da a. The inal con e ence o he ESF Genomic Resou ces p og am aimed o add ess B u o d e al. Challenges in li es ock conse a ion hese in e disciplina y p oblems in an a emp o con ibu e o he agenda o esea ch and policy de elopmen di ec ions du ing he coming decade. By 2020, acco ding o he Con en ion on Biodi e si y’s Aichi Ta ge 13, signa o ies should ensu e ha “… he gene ic di e si y o … a med and domes ica ed animals and o wild ela i es …is main ained, and s a egies ha e been de eloped and implemen ed o minimizing gene ic e osion and sa egua ding hei gene ic di e si y.” Howe e , he eal ex en o gene ic e osion is e y di icul o measu e using cu en da a. The e o e, his challenging a ge demands be e co e age, unde s anding and u iliza ion o genomic and en i onmen al da a, he de elopmen o op imized ways o in eg a e hese da a wi h social and o he sciences and policy analysis o enable mo e lexible, e idence-based models o unde pin FAnGR conse a ion. A he con e ence, we a emp ed o iden i y he mos impo an p oblems o e ec i e li es ock genomic esou ce conse a ion du ing he nex decade. Twen y p io i y ques ions we e iden i ied ha could be b oadly ca ego ized in o challenges ela ed o me hodology, analy ical app oaches, da a managemen and conse a ion. I should be acknowledged he e ha while he ocus o ou mee ing was p edominan ly a ound gene ics, genomics and animal science, many o he p ac ical challenges acing conse a ion o genomic esou ces a e socie al in o igin and a e p edica ed on he alue (e.g., socio-economic and cul u al) o hese esou ces o a me s, u al communi ies and socie y as a whole. The o e all conclusion is ha despi e he ac ha he li es ock sec o has been ela i ely well-o ganized in he applica ion o gene ic me hodologies o da e, he e is s ill a la ge gap be ween he cu en s a e-o - he-a in he use o ools o cha ac e ize genomic esou ces and i s applica ion o many non-comme cial and local b eeds, hampe ing he consis en u iliza ion o gene ic and genomic da a as indica o s o gene ic e osion and di e si y. The li es ock genomic sec o he e o e needs o make a conce ed e o in he coming decade o enable o he democ a iza ion o he powe ul ools ha a e now a i s disposal, and o ensu e ha hey a e applied in he con ex o b eed conse a ion as well as de elopmen . Keywo ds: a m animal gene ic esou ces, li es ock gene ic esou ces, genomic di e si y, li es ock popula ion p io i iza ion, e ec i e conse a ion policy INTRODUCTION Unde s anding cu en echnical, in as uc u al and policy challenges and assessing he likely bene i s o o e coming hem in he u u e is essen ial o any ield o scien i ic endea o and especially hose wi h clea socie al consequences and po en ial bene i s. In his con ex , he concep o ho izon scanning has been de eloped and applied annually in he ield o biodi e si y conse a ion since 2009 (Su he land and Wood oo , 2009), using a a ie y o sys ema ic and semi-sys ema ic me hods o mine ending issues om web engines and social media and by analyzing ocused ques ionnai es. Simila app oaches ha e also been aken o iden i y eme ging issues in ag icul u e (P e y e al., 2010) and ela ed ields such as soil science, ood sys ems and pollina ion (Dicks e al., 2013; Ing am e al., 2013; Adewopo e al., 2014). Such exe cises ha e iden i ied a numbe o issues o ele ance o he conse a ion o FAnGR, such as gene ic con ol o in asi e species (Su he land e al., 2014) and sus ainable in ensi ica ion o high yielding ag icul u e (Su he land e al., 2015). In 2010, P e y e al.’s a icle pinpoin ing he “Top 100 ques ions o impo ance o he u u e o global ag icul u e” iden i ied gene ic issues in c op imp o emen (e.g., gains in imp o emen ha could esul om b eeding o s ess ole ance) bu iden i ied no such p essing agendas o li es ock genomic esou ces. Since Ca dellino and Boyazoglu (2009) no a emp has been published o iden i y esea ch p io i ies o FAnGR conse a ion, despi e gene ic e osion (sensu Aichi Ta ge 13) con inuing apace (e.g., Be houly-Salaza e al., 2012; FAO, 2015a) and he s ep-change ha has occu ed in molecula b eed cha ac e iza ion since he ou ine implemen a ion o li es ock Single Nucleo ide Polymo phism (SNP) a ays. To ill his gap, a cen al ac i i y o he Final Con e ence o he Eu opean Science Founda ion’s Genomic Resou ces p og am, held a Ca di Uni e si y June 17 h–19 h 2014 was o pick ou a se ies o p essing ques ions ha could o m pa o a esea ch and policy agenda o FAnGR conse a ion o he nex decade. While no ollowing he s anda d sys ema ic app oaches adop ed by con en ional Ho izon Scanning exe cises, all 43 a endees o his ocused mee ing ook pa in he exe cise, including scien is s and policy-make s om Sou h and Eas Asia, No h Ame ica, Eu ope F on ie s in Gene ics | www. on ie sin.o g 2Oc obe 2015 | Volume 6 | A icle 314 B u o d e al. Challenges in li es ock conse a ion and A ica in ol ed in a ange o disciplines om genomics o animal b eeding, gene ic esou ce managemen , economic and social sciences and global ag icul u al policy de elopmen . METHODS AND RESULTS Du ing he cou se o he con e ence, a endees we e asked o con ibu e up o i e ques ions o highes p io i y o esea ch, in as uc u e and policy de elopmen du ing he coming decade. Eigh y-six sugges ions we e ecei ed. The issue iden i ied wi h highes equency (18 imes) was he need o “nex gene a ion pheno yping” (i.e., high- h oughpu me hods o collec and summa ize de ailed pheno ypic da a om domes ic animals). A summa y o he op 20 ques ions is ound in Table 1, a subse o which a e p esen ed below (some a e amalgama ed). All esponses we e ca ego ized in o ou majo g oups, “Me hodological Challenges,” “Analy ical Challenges,” “Da a Managemen ,” and “Conse a ion Managemen and P io i iza ion.” Fou wo king g oups we e con ened o co e hese ca ego ies and hei indings a e p esen ed below. Me hodological Challenges Nex Gene a ion Pheno yping The need o high- esolu ion pheno ypic da a o be collec ed o in-dep h cha ac e iza ion o FAnGR was iden i ied, especially in ligh o he apid ad ances ha ha e been made in molecula b eed cha ac e iza ion. De eloping me hods o pheno ypic cha ac e iza ion was also iden i ied by Ca dellino and Boyazoglu (2009) ollowing om FAO ecommenda ions (FAO, 2007a) and has clea ly emained an unde -explo ed esea ch a ea. Howe e , wi h he ichness o molecula da a inc easing d ama ically since 2009, he misma ch be ween molecula and pheno ypic da a is widening o all excep highly comme cial ansbounda y b eeds and lines wi h genomic b eeding alues. Inhe en in high- esolu ion b eed cha ac e iza ion is a need o de ine key pheno ypic ai s and cha ac e is ics (pa icula ly hose po en ially in ol ed in local adap a ion) based on guidelines ha can be used as common measu es o such s udies wi h s ingen ield p o ocols o hei collec ion. FAO published guidelines on pheno ypic cha ac e iza ion (FAO, 2012a). In his way mo e compa able da a can be gene a ed, and b eed cha ac e iza ion can ha e a mo e unc ional basis, especially wi h he u gen need o unde s and b eed cha ac e is ics in he ace o clima e change (Ho mann, 2010). Also an imp o ed desc ip ion o he speci ic p oduc ion en i onmen and epidemiological his o y in which popula ions o a b eed a e kep would allow be e compa ison o pheno ypes and pe o mances (e.g., FAO, 2009). Since b eed cha ac e iza ion can be a cos ly exe cise, especially o emo e egions o he wo ld, as many pheno ypic ai s as possible should be collec ed ollowing well documen ed and ep oducible p ocedu es, a p ocess ha calls o he need o s anda dized me hods o measu e/collec da a and ul ima ely o aining o people on how o do i . Whe e possible, da a should be made publicly a ailable h ough a eposi o y such as FAO’s global Domes ic Animal Di e si y In o ma ion Sys em DAD-IS (h p://dad. ao.o g) o compa a i e pu poses. The es ablishmen o a wo king g oup o de ine guidelines, p o ocols and ools o collec ing such da a unde he auspices o he FAO, In e na ional Socie y o Animal Gene ics o he In e na ional Commi ee o Animal Reco ding (www.ica .o g) would accele a e his p ocess. Omics Da a and Associa ion S udies The d ama ic accele a ion in genome sequencing means ha all domes ica ed species and hei ew emaining wild ela i es will become genome-enabled in he coming decade (e.g., Qiu e al., 2012; Wu e al., 2014). Re e ence genomes p o ide he basis o de elopmen o genome-wide assays o a ia ion in less commonly a med and/o mo e egionally dis ibu ed li es ock species and popula ions using SNP a ays, as ha e been de eloped and made a ailable o comme cial li es ock in he pas 5 yea s (e.g., Ma ukumalli e al., 2009). The choice o SNPs o inclusion in a ays o less comme cial popula ions may be expec ed o ocus on a wide a ay o ai s han o comme cial/ ansbounda y b eeds, such as hose ela ed o local adap a ion, disease esis ance, d ough ole ance and niche p oduc cha ac e s, bu in p ac ice his could be hampe ed by a lack o eliable pheno ypic da a. To enable SNP a ays o be de eloped in a apid, cos e ec i e and widely applicable manne , he iden i ica ion o common e e ence genomes and es panels o indi iduals o a ay de elopmen and di e si y s udies is key. Howe e , i is impo an o no e ha wi h he apidly alling cos o whole genome esequencing (e.g., Lee e al., 2013; Zhang e al., 2015) using nex gene a ion echnologies and he a ailabili y o e en lowe cos geno yping by sequencing (GBS: De Dona o e al., 2013) being a ailable, he p oblem o asce ainmen bias can be mi iga ed agains since hey allow he iden i ica ion and di ec es ima ion o SNP di e si y o FAnGR popula ions, b eeds o species a easonable p ices. Indeed hese me hods a e su icien ly cos -e ec i e now, ha hey can be in p inciple used as s anda d assaying app oaches, wi h a cos in he low ens o dolla s o GBS now easible o analysis o ens o housands o SNPs. A majo issue iden i ied o genome-wide associa ion s udies (GWAS) is expe imen al design including, bu no con ined o, sample size conside a ions (Kada mideen, 2014) and he a ailabili y o di e en SNP geno yping a ays o some species and hei compa ibili y o lack he eo (Nicolazzi e al., 2015). Cha ac e iza ion o en i onmen al pa ame e s in ex ensi e p oduc ion sys ems is ano he key challenge o GWAS bu may be assis ed by he applica ion o E(en i onmen )WAS me hodologies as applied in humans (e.g., Pa el e al., 2010). Addi ionally, unde s anding he ole o he epigenome and i s ole in en i onmen -dependen pheno ypic di e si y and plas ici y is becoming an inc easing ocus in li es ock gene ics (e.g., Jammes and Rena d, 2010; Magee e al., 2011, 2014). Ul ima ely, he in eg a ion o genomic, epigenomic, ansc ip omic, and en i onmen al da a will be equi ed i meaning ul la ge-scale s udies a e o be success ul in iden i ying selec ion and conse a ion a ge s in he e ogeneous en i onmen s (Jones e al., 2013; Wu e al., 2014) and in sc u inizing he biological basis o adap a ion, esilience, and e en animal imp o emen . Non-au osomal Inhe i ance Non-au osomal inhe i ance (Y-ch omosomal, X-ch omosomal, and mi ochond ial) is a compa a i ely neglec ed a ea o F on ie s in Gene ics | www. on ie sin.o g 3Oc obe 2015 | Volume 6 | A icle 314 B u o d e al. Challenges in li es ock conse a ion TABLE 1 | Summa y o he Top 20 ques ions in a m animal genomics esea ch iden i ied by he pa icipan s o he Ca di symposium. Ques ion # 1. Nex gene a ion pheno yping The misma ch be ween molecula and pheno ypic da a has inc eased d ama ically. Which key pheno ypic ai s should be used as common measu es o di e si y s udies o de ine b eed cha ac e is ics in he ace o clima e change? 2. Genome-wide SNP assays The iden i ica ion o common e e ence genomes and es panels o indi iduals o SNP a ay de elopmen in less comme cial and/o local popula ions is key. Which s a egy shall be used o enable SNP a ays o be de eloped in a apid, cos e ec i e and widely applicable manne ? 3. Re e ence genomes Which common e e ence genomes and es panels o indi iduals should be used o a ay de elopmen and di e si y s udies? 4. E(en i onmen )WAS How o cha ac e ize en i onmen al pa ame e s in ex ensi e p oduc ion sys ems? 5. Epigene ics How can epigenomic in o ma ion be in eg a ed wi h pheno ypic and genomic da a o sc u inize he biological basis o adap a ion and plas ici y/ esilience in li es ock popula ions? 6. Male-media ed gene ic di e si y Which me hodological app oach can be applied o p omo e eliable assembly o he Y-ch omosome, s ill lacking o many li es ock species, as well as o de elop polymo phic Y-ch omosome ma ke s? 7. Ancien DNA and paleoen i onmen al analyses Which s a egies should be ollowed o collec zooa chaeological specimens om c i ical geog aphic si es and p omo e he analysis o ancien genomes? 8. Conse a ion o genomic di e si y How o design a managemen p og am ha e alua es genomic egions o conse a ion? 9. Polygenic adap i e and economic ai s Haplo ypes s. SNPs: in which si ua ions do one o he o he p o ide a mo e e icien uni o di e si y in QTL egions? 10. Mic osa elli es (STRs) s. SNPs How o in eg a e da a om he STRs and SNPs, and how o manage he ansi ion om STR- o SNP-based cha ac e iza ion o FAnGR? 11. GW di e si y s a is ics Which combina ion o pa ame e s will be equi ed o adequa ely summa ize genome di e si y? 12. Da a managemen How can links be ween majo FAnGR da abases be p omo ed o be able o ede a e esou ces and ac as an educa ional cen al poin ? 13. Da a a ailabili y Which o ma should be used o make NGS, pheno yping and GIS da a publicly a ailable, and how can indus y con ibu e owa d popula ion and main enance o such da abase? 14. Pa icipa o y p ojec s How can pa icipa o y p ojec s, including ci izen science, o example, he use o sma -phone echnologies be encou aged o enable da a collec ion on FAnGR a a la ge scale? 15. P io i iza ion o conse a ion Why a e p io i iza ion me hods no being applied by policy make s and manage s and is he e a lack o dissemina ion o pene ance? 16. Genomic p io i iza ion How o implemen genomic app oaches sys ema ically in conse a ion p io i iza ion o include genes impo an in unc ionally aluable ai s? 17. U iliza ion in p ac ice How o econcile he cos o genomic analysis s. he economic e u ns on geno yped s ock o allow o a wide use o genomic da a o assis conse a ion, p oduc ion and managemen o FAnGR? Wha is he demand and willingness o pay wi hin he sec o ? 18. Sys ema ic collec ion How o ensu e ha gene ic and genomic da a a e collec ed su icien ly sys ema ically o be applied o new indica o s? 19. De ining goals Which indica o s can be applied o mos e icien ly moni o gene ic ends in domes ic popula ions? 20. S a egic app oach How will he la es ad ances in ‘omics echnology con ibu e o achie e he ul ima e goal o hal ing he loss o biodi e si y o FAnGR? F equencies a e no included o each ques ion and he ques ions a e no lis ed in ank o de . esea ch in li es ock conse a ion. While s udies o non- au osomal gene ic ma ke s ha e been ex ensi ely used in s udies o e olu iona y his o y, bo h singly and combined (e.g., Gö he s öm e al., 2005; Meadows and Kijas, 2008; S ensson and Gö he s öm, 2008; Pe ei a e al., 2009; Ramí ez e al., 2009; Ginja e al., 2010; G oene eld e al., 2010), hei exploi a ion in genomic s udies has been somewha o e looked in compa ison o au osomal ma ke s in many li es ock species. This o e sigh is su p ising gi en he well- documen ed links be ween mi ochond ial sequence a ia ion and i ness in human popula ions (e.g., Wallace, 2005) and he inc easingly ecognized ole ha Y-ch omosomal a ia ion plays in male e ili y in li es ock (e.g., Chang e al., 2013; Yue e al., 2014). Technical challenges ha e long been acknowledged wi h inding polymo phic ma ke s on he Y-ch omosome in mammals and W-ch omosome in bi ds, howe e such ma ke s, al hough elusi e, ha e been shown o p o ide no el insigh s in o li es ock di e si y when a ailable (e.g., Edwa ds e al., 2011; Wallne e al., 2013), and should be used as a ma e o cou se o p o ide a male/ emale pe spec i e on li es ock genomic di e si y. Ancien DNA S udies Al hough i mly es ablished as a majo ou e in o a deepe unde s anding o li es ock e olu ion and di e si y (e.g., La son e al., 2010), ancien DNA (aDNA) s udies ha e been hampe ed by a numbe o cons ain s. These include limi ed access o samples om geog aphic a eas whe e (local) domes ica ion may ha e aken place (e.g., A ica, Nea Eas , Asia, Sou h Ame ica), limi ed da a sha ing among hose g oups wo king on samples om c i ical si es (bu see A buckle e al., 2014) and limi ed success a es, especially o genome-wide s udies. None heless, ecen ly de eloped me hodological and bioin o ma ics ools allowed o inc eased accu acy in he analysis o high- h oughpu ancien DNA da a and e en he cha ac e iza ion o comple e F on ie s in Gene ics | www. on ie sin.o g 4Oc obe 2015 | Volume 6 | A icle 314 B u o d e al. Challenges in li es ock conse a ion genomes o Pleis ocene ho ses (O lando e al., 2013). Also, al e na i e sou ces o ma e ial such as pa chmen a e, howe e , p o iding p omising ou comes (Teasdale e al., 2015). Exci ing oppo uni ies ha e ecen ly been opened up by he disco e y o li es ock DNA in lake sedimen samples in Lake An e ne, Swi ze land (Gigue -Co ex e al., 2014), which enabled a di ec compa ison o be made o he paleoen i onmen wi h changes in his en i onmen due o he a i al o a ming and domes ic li es ock, and could be applied o desc ibe his o ic luc ua ions in ag icul u al in ensi y and p ac ice and, exci ingly, may e en allow he possibili y o p edic i e modeling o he p esence/absence o sui able ag i-habi a unde u u e clima e change scena ios. Analy ical Challenges Conse a ion o Genomic Di e si y The concep o genome conse a ion has been discussed ex ensi ely in he li e a u e bu ad ances in genome da a and echnologies only now allow he de elopmen o b eed managemen p og ams able o achie e his aim. Fo example, He e o-Med ano e al. (2014), using genome esequencing and SNP a ays disco e ed almos 100 non-synonymous polymo phic nucleo ides nea ly ixed in comme cial pig b eeds bu wi h an al e na i e allele in non-comme cial popula ions, a ec ing 65 genes in o al. Such genomic polymo phisms could all in o a ca ego y o hose ha “canno a o d o be los ” om less comme cial local b eeds, gi en hei dis inc i eness and he alue hey po en ially ep esen as a gene ic esou ce o al e na i e selec ion should he p oduc ion en i onmen change (K is ensen e al., 2015). Howe e , o design a managemen p og am ha e alua es genomic egions o conse a ion, no only do polymo phisms need o be iden i ied, he unc ional a chi ec u e o hose genomic egions and he genes hey con ain needs o be assessed and he in e ac ion among hose genes needs o be conside ed. Recen ly, a s udy o chicken b eeds examined unc ional a ia ion in copy numbe a ian s (CNV) a o e 200 genes o e lapping 1000 quan i a i e ai loci, including some pu a i ely in ol ed in ai s such as skin colo and skele al cha ac e is ics (Han e al., 2014). Haplo ype Blocks s. Indi idual SNPs Ob aining an accu a e desc ip ion o he gene ic polymo phisms explaining a ai o e olu iona y, adap i e and/o economic impo ance is no a i ial ask, as ai s subs an ially a y in he numbe o polymo phisms in ol ed in hei pheno ype and whe e hese occu ac oss he genome (Godda d and Hayes, 2009; Olson-Manning e al., 2012). Fo example, many o such ai s a e polygenic and dis ibu ed a ound he genome, making whole-genome esequencing, and medium and high-densi y SNP a ays a powe ul app oach o loca ing hem and elucida ing hei a ia ion (e.g., Huang e al., 2010). Howe e , o ce ain linked ai s, haplo ypes may p o ide a mo e e icien uni o assessing di e si y in QTL egions han indi idual SNPs (e.g., Kijas e al., 2013; Bosse e al., 2014a,b; Mok y e al., 2014), e lec ing local genomic a chi ec u e in a mo e accu a e ashion. Consequen ly, a he ini ial s ages o s udies aiming o iden i y he gene ic basis o pheno ypic a ia ion, gene al genome-wide SNP analyses may be mo e sui able. I is wo h no ing, howe e , ha phasing haplo ypes in di e gen popula ions lacking complemen a y pedig ee da a p esen s a non- i ial challenge. Haplo ype analysis can p o ide an especially powe ul ool o in es iga e he hyb id o igin o domes ica ed popula ions. Fo ins ance, mode n Wes e n comme cial pig genomes a e a mosaic o Eas e n and Wes e n Eu asian biogeog aphic o igin. Admix u e mapping allows he “so ing” o haplo ype segmen s o hei pu a i e o igin. In addi ion, his s a egy has been shown o be powe ul o in e selec ion on speci ic haplo ypes pos -hyb idiza ion (Bosse e al., 2014a,b). Managing he T ansi ion om Mic osa elli e o SNP Da a The ansi ion om mic osa elli e ma ke s o SNPs has happened apidly in FAnGR o comme cial/ ansbounda y b eeds due o he a ailabili y o ela i ely inexpensi e 50K SNP geno yping a ays o mos common li es ock species (Ma ukumalli e al., 2009). Howe e , SNP a ays a e no ye a o dable ools o much o he wo ld’s FAnGR and a e no ye a ailable o all species (see abo e). This he e o e aises he immedia e p oblem o how o in eg a e da a om he wo ma ke ypes and how o manage he ansi ion om mic osa elli e-based FAnGR cha ac e iza ion (much o which has been ca ied ou using ma ke s ecommended by ISAG, FAO, 2011) o SNP- based cha ac e iza ion. One op ion is o e-geno ype many o he b eeds ha al eady ha e mic osa elli e geno ypes wi h SNPs (Ajmone-Ma san e al., 2014), bu his would be expensi e and i implemen ed would aise he ques ion as o whe he he new da a would again be eplaced by a newe echnology (e.g., whole- genome esequencing). P agma ically, i seems ha mic osa elli e da a a e pe ec ly adequa e o es ima ing gene ic di e si y and desc ibing demog aphic ela ionships (e.g., Fe ando e al., 2014). Howe e , o cos easons he ull se o mic osa elli e ma ke s was equen ly no applied, especially in de eloping coun ies. Also, mic osa elli e da a will no be as e icien o enabling he iden i ica ion and a ge ed conse a ion o genomic egions unde selec ion since da a a e usually p oduced wi h a ew ens o quasi-neu al ma ke s (e.g., He e o-Med ano e al., 2013). Ne e heless, i is becoming clea ha da a p oduced using SNP a ays a e mo e epea able and do no su e om sco ing di e ences ha ha e made he combina ion o mic osa elli e da ase s some imes p oblema ic and equi ing s a is ical e alua ion (Lens a e al., 2012). Pa adoxically, whole genome esequencing may become he mos eliable and cos e ec i e way o analyse genomic di e si y in he u u e, e en o non-comme cial b eeds, i he cos comes down by ano he o de o magni ude (as may happen wi h po able sequence s such as Ox o d Nanopo e’s MiniION sys em), p o iding he ad an age o no longe needing o use a se o SNP ma ke s asce ained om comme cial popula ions. Genome-wide Di e si y S a is ics The eme gence o whole genome sequencing and medium-high densi y SNP a ays means ha summa izing gene ic di e si y can now be a mo e nuanced and genomic egion-speci ic exe cise. I is well known ha asce ainmen bias o SNP a ays can s ongly unde es ima e he di e si y o he (usually au och honous and F on ie s in Gene ics | www. on ie sin.o g 5Oc obe 2015 | Volume 6 | A icle 314 B u o d e al. Challenges in li es ock conse a ion less comme cial) b eeds no used o design he a ays (Po o Ne o and Ba endse, 2010). This phenomenon does no impac on whole-genome esequencing as all polymo phisms a e cap u ed p o ided su icien sequence dep h is achie ed. A combina ion o pa ame e s will be equi ed o adequa ely summa ize genome di e si y (e.g., he e ozygosi y and e ec i e popula ion size and inb eeding), as no single all-encompassing s a is ic o summa ize all o a popula ion’s genomic di e si y and his o y exis s, despi e o how emp ing i may be o de ine such s a is ic (e.g., o policy make s). E ec i e popula ion size (Ne) es ima es can be ob ained wi h as li le as a single genome using me hods such as he Pai wise Sequen ial Ma ko ian Coalescen , al hough hese analyses can p o e inconclusi e i genome co e age is insu icien o i admix u e pe ains (Li and Du bin, 2011; O ozco- e Wengel and B u o d, 2014; Schi els and Du bin, 2014; F an z e al., 2015). Fo ecen ly e ol ed popula ions, such as many domes ic species, linkage disequilib ium-based (LD) es ima es may be mo e accu a e and me hods a e now eme ging o ca y ou hese analysis (e.g., Ba ba o e al., 2015). Runs o homozygosi y (ROH; e.g., Bosse e al., 2012; Sc aggs e al., 2014) unc ions desc ibing he dis ibu ion o homozygosi y h oughou he genome may also se e as a obus genome-scale Ne es ima o in he u u e, al hough in e p e a ion and scaling depends on he local ecombina ion. ROH a e al eady used as a genomic p oxy o inb eeding (e.g., Pu ield e al., 2012; Cu ik e al., 2014), including o speci ic genome- loca ed ai s (P yce e al., 2014). This app oach p omises o be an e icien way o a oid he p oduc ion o o sp ing homozygous o dele e ious alleles a speci ic genomic egions ha a e associa ed wi h inb eeding dep ession (P yce e al., 2014). Da a Managemen Da a Accessibili y As also iden i ied by Ca dellino and Boyazoglu (2009) he e emains a majo need o p o ide much be e links be ween he majo FAnGR da abases, which ha e la gely been se up independen ly and a e b eed- ocused (G oene eld e al., 2010). The li es ock genomics communi y needs ei he o build on an exis ing pla o m (such as he ARKDB, h p://www. hea kdb. o g/a kdb/ and he Eu opean Nucleo ide A chi e, h p://www. ebi.ac.uk/ena), ha ha e some le el o connec i i y, e.g., wi h Ensembl (h p://www.ensembl.o g/index.h ml) o o es ablish an independen communi y-based ini ia i e(s) unde he o m o a use - iendly global web po al and would include web se ices able o ede a e esou ces and ac as an educa ional cen al poin . Such esou ces a e al eady being de eloped, including he Adap map p ojec o goa s (h p://www.goa adap map. o g/). In o ma ion on li es ock ela ed da a should be made a ailable and use ul ecommenda ions a e equi ed o in o m s akeholde s on how o eco d da a, and whe e o s o e wha ype o in o ma ion. In pa icula , i is impo an o p omo e wi hin he communi y o use s ha aw and me a-da a a e key componen s and ha hey should be made a ailable in public da ase s oge he wi h elabo a ed da ase s. When he e a e exis ing public esou ces o a gi en da a ype such as hose lis ed abo e, hey should be used o hei abili y o se s anda ds and cen alize da a access. Fo o he da a ypes, open digi al eposi o ies such as D yad (h p://da ad yad.o g/), Zenodo (h ps://zenodo.o g/), o igsha e (h p:// igsha e.com/) comp ise in aluable ools ac ing as incen i es o people o main ain and upg ade hei da ase s as da a can be submi ed and au ho s a e p o ided wi h a e e ence which can be ci ed. This da a ecosys em becomes especially impo an wi h he my iad o SNP a ay da ase s ha a e now a ailable and he incompa ibili y among di e en e sions o hese a ays wi hin he same species (Nicolazzi e al., 2015). Mo eo e , o add alue o gene ic esou ces, ede a ing gene bank esou ces is one s ep ha needs o be comple ed by explici connec ion— h ough geog aphical coo dina es—wi h pheno ypic da a, bu also wi h socio-economic, socio-demog aphic, clima ic, en i onmen al, and policy in o ma ion. This equi es links o exis ing online digi al esou ces (Joos e al., 2010) ha a e cu en ly a ely used by he FAnGR communi y and need o be lis ed on such a global po al. Da a A ailabili y While many geno yping p ojec s on comme cial li es ock b eeds a e unded by indus y, ende ing all excep summa y da a una ailable in many cases, in p inciple aw da a om publicly unded p ojec s should be made publicly a ailable. Indeed, when da a a e open, i i s makes he in o ma ion mo e c edible, makes da a e-usable, and also enables ep oducibili y an impo an scien i ic p inciple (E z e al., 2014). Inc easingly, in e na ional conso ia, such as FAANG on animal unc ional genomics ollow he To on o p o ocol and immedia ely place da a in he public domain (h p://www. aang.o g; The To on o In e na ional Da a Release Wo kshop Au ho s, 2009; Ande sson e al., 2015). A nex gene a ion pheno yping da abase should also be es ablished, including GIS and anonymized a m le el da a, animal pho og aphs and me a-da a— his could pa ly ollow he o ma o he EU FP5 p ojec Econogene (h p://www. econogene.eu) and would be mos e icien ly linked wi h FAO’s DAD-IS and EFABIS (h p://e abis. z . al.de). The owne ship and hos ing o such a esou ce would be logis ically and inancially challenging, and could p o ide an oppo uni y o he ag i-indus y o con ibu e owa d conse a ion o he gene ic esou ces i has u ilized in he pas and may need again in he u u e. This could also be pa o he communi y-based ac ion men ioned abo e, wi h many ad an ages (logis ic and unding), bu equi ing a s ong leade ship. An app oach o da a esou cing such has been exempli ied wi h human da a by he 1000 Genomes p ojec (h p://www.1000genomes.o g) and he 1001 A abidopsis genomes esou ce (h p://1001genomes. o g wi h da a being publicly a ailable ei he immedia ely o a e an ag eed emba go pe iod, could be e y applicable o li es ock s udies. Fo example, he esequencing da a om he EU F amewo k 7 Nex gen p ojec was made a ailable sho ly a e he p ojec ’s comple ion a he Eu opean Bioin o ma ics Ins i u e’s FTP si e ( p:// p.ebi.ac.uk/pub/da abases/nex gen/). Pa icipa o y P ojec s Many indi iduals who a e in e es ed in FAnGR a e in ol ed in ag icul u e as smallholde s, a me s, b eede s, and p oduce s F on ie s in Gene ics | www. on ie sin.o g 6Oc obe 2015 | Volume 6 | A icle 314 B u o d e al. Challenges in li es ock conse a ion and many o hese a e no o mally in ol ed in b eeding p og ams and li es ock conse a ion, ye main ain an in e es h ough ag icul u al shows and a me s’ ma ke s (e.g., Zimme e , 2010; Johns e al., 2013). A he same ime, he ole o pa icipa o y app oaches and mobile echnology po en ially enables obus da a collec ion on a p e iously unimaginable scale (Lisson e al., 2010; Teache e al., 2013; Sambo e al., 2015). Use o c owdsou cing should he e o e be encou aged in FAnGR as should use o sma -phone apps and echnologies o pho og aphy, da a s o age and sampling (e.g., “do- o ms” h p:// www.do o ms.com). A logical combina ion o hese ini ia i es lies in he possibili y o a li es ock communi y independen ini ia i e, including web se ices o ede a e hese da a sou ces, o ca y ou quali y con ol and p o iding a cen al access poin o da a bu also in o ma ion o educa e people on how o eco d FAnGR da a. Such app oaches could also help in secu ing unds o p ojec s in FAnGR popula ions and b eeds, which o en ace he p oblem o secu ing unds o ca y ou his necessa y esea ch. Conse a ion, Managemen , and P io i iza ion Is P io i iza ion a P io i y? A pa adigm wi hin FAnGR o he pas 15 yea s conce ns he use o gene ic da a, alongside o he in o ma ion in p io i iza ion o li es ock popula ions and b eeds o conse a ion (Wei zman, 1992; Simiane e al., 2003; Boe che e al., 2010; Ginja e al., 2013). Howe e , he e is limi ed e idence ha his app oach is being applied sys ema ically ac oss coun ies epo ing o he FAO, al hough he second epo on he S a e o he Wo ld’s Animal Gene ic Resou ces has documen ed ac i i ies o some ex en (FAO, 2015b,c). I , howe e , p io i iza ion me hods a e no being applied by manage s and policy- make s, he ques ion needs o be asked as o why? A numbe o explana ions may pe ain: i s , he me hod(s) may ha e no gained enough ac ion wi h policy make s o ensu e i s/ hei implemen a ion, which may indeed be because genomic me hods, which ha e ye o be sys ema ically implemen ed, will la gely supe sede he mic osa elli e-based app oaches implemen ed hus a and enable conse a ion p io i iza ion o include genes impo an in unc ionally aluable ai s (e.g., To o e al., 2014). Fu he mo e, p io i iza ion on he basis o gene ic dis ances (Wei zman, 1992) is con ounded by gene ic isola ion o b eeds (Eu opean Ca le Gene ic Di e si y Conso ium, 2006). Second, p io i iza ion may no ac ually be needed, a leas in ce ain egions, whe e b eed socie ies a e ac i e and all o mos o he b eeds can be main ained. Howe e , ecen animal heal h eme gencies (e.g., ou b eaks o ansmissible spongi o m encephalopa hies, TSEs) ha e cas doub on his simplis ic scena io and equi ed he applica ion o ca e ul gene ic managemen du ing and a e he ou b eak. While p io i iza ion may be less o a p io i y in he wo ld’s iches egions, i is no expec ed o be he case in de eloping coun ies, whe e ex inc ion may ake a numbe o o ms, including gene ic e osion (e.g., Be houly-Salaza e al., 2012; FAO, 2015a,b). Finally, he me hods de eloped may no ha e been applied because policy make s and manage s a e unawa e o hei a ailabili y, which could be due o a lack o dissemina ion o pene ance o educa ional ma e ial o he decision make s. U iliza ion in P ac ice While esea ch and applica ion o genomic ools in li es ock is occu ing in many comme cial/ ansbounda y b eeds (e.g., P yce e al., 2014; Sc aggs e al., 2014), i s applica ion in less comme cial popula ions is spo adic and he scien i ic basis o decisions on managemen o indigenous li es ock, o example in which ge mplasm o s o e, assessing he e ec s o upg ading o e alua ing ongoing gene ic managemen is he e o e highly a iable (e.g., B own e al., 2014; FAO, 2015b). This poin s o he eali y ha gene ically-based p io i iza ion is unlikely o be ope a ional in he absence o o he conside a ions, including comme cial eali y and he ecosys em/p oduc ion en i onmen (e.g., Sande son e al., 2013). The use o genomic da a o manage FAnGR wi hin b eeds is howe e , con inuing apace (see abo e) and can be demons a ed o be assis ing conse a ion, p oduc ion and managemen in many cases (e.g., He e o-Med ano e al., 2014; Sc aggs e al., 2014). Howe e , o many b eeds he cos o gene ic/genomic analysis s. he po en ial economic e u ns on geno yped s ock (wi h a ew excep ions such as TSE esis ance) makes i s applica ion uneconomic, and he e o e i is o en no applied. I is unlikely ha geno yping cos s will each he le el o economic iabili y o many FAnGR, howe e his assump ion should be es ed by some a ge ed esea ch ac oss he sec o . De ining Goals The Con en ion on Biological Di e si y’s Aichi Ta ge 13, which ecommends ha : “s a egies ha e been de eloped and implemen ed o minimizing gene ic e osion and sa egua ding gene ic di e si y” is e lec ed in he Ta ge o S a egic P io i y A ea 4 o he Global Plan o Ac ion o Animal Gene ic Resou ces (FAO, 2007b). These esou ce indica o s con ibu e o he measu emen o p og ess owa d Aichi Ta ge 13 (FAO, 2012b) and a e calcula ed a na ional, egional and global le els, based on da a en e ed by Na ional Coo dina o s o he Managemen o Animal Gene ic Resou ces1 (172 coun ies had nomina ed a Na ional Coo dina o as o July, 2014) in o he Domes ic Animal Di e si y In o ma ion Sys em (DAD-IS). The ollowing indica o s ha e been ag eed by he Commission on Gene ic Resou ces o Food and Ag icul u e: • he numbe o locally adap ed b eeds; • he p opo ion o he o al popula ion accoun ed o by locally adap ed and exo ic b eeds; and • he numbe o b eeds classi ied as a isk, no a isk and unknown. The Global Da abank o Animal Gene ic Resou ces, he backbone o DAD-IS, enables Na ional Coo dina o s o en e b eed-speci ic da a, including da a on he size and s uc u e o b eed popula ions, equi ed o calcula e hei isk s a us. FAO 1The lis o Na ional Coo dina o s o he Managemen o Animal Gene ic Resou ces is ound a dad. ao.o g/cgi-bin/E abisWeb.cgi?sid=-1,con ac s. F on ie s in Gene ics | www. on ie sin.o g 7Oc obe 2015 | Volume 6 | A icle 314 B u o d e al. Challenges in li es ock conse a ion p oduces biannual S a us and T ends Repo s (FAO, 2015a). Fo he i s epo on The S a e o he Wo lds Animal Gene ic Resou ces, a isk s a us classi ica ion based on popula ion size da a was used. The (lack o ) a ailabili y o global da a cu en ly makes a mo e elabo a e sys em in ol ing, o example, molecula di e si y indices, popula ion s uc u e/ agmen a ion, pedig ee da a, numbe and size o he ds, and geog aphic dis ibu ion inope able. While genomic me hods migh help o o e come hese da a de iciencies, i hey a e o be applied o li es ock conse a ion, i is impo an o de ine he goals o such app oaches and how he da a could be used o imp o e o augmen he cu en se o indica o s using da a ha could be collec ed on ends in e ec i e popula ion size, admix u e, inb eeding and genome-wide di e si y. The wide applica ion o such da a hinges on hei applicabili y o au och onous, less- comme cial b eeds. Un o una ely, he da a cu en ly p o ided o FAO does no e en allow he eliable calcula ion o basic ends cu en ly measu ed ia he abo e indica o s (Ti enso e al., 2014; FAO, 2015a), ye he li es ock gene ics and conse a ion communi y possess many o he ools needed o di ec ly e alua e whe he signa o ies o he CBD a e “.. .minimizing gene ic e osion” and “sa egua ding gene ic di e si y” (CBD Ta ge 13). Two key de elopmen s a e equi ed o enable he cu en app oach o mo e di ec ly use gene ic o genomic da a in he u u e: i s , he li es ock conse a ion gene ics communi y mus he e o e insis ha da a a e collec ed and analyzed in such a way ha esul s a e di ec ly compa able and second, o help de elop be e indica o s applied o moni o ing gene ic ends in domes ic popula ions. CONCLUSION Any exe cise designed o assess he s a e-o - he-a in a scien i ic ield only manages o cap u e a b ie momen in ime, which is why he Ho izon scanning exe cises ca ied ou in biodi e si y conse a ion a e epea ed e e y yea (see Su he land e al., 2015). He e, we a emp ed o ake a longe - e m (decadal) iew o genomic esou ces conse a ion, and du ing his pe iod, some majo miles ones will be passed. Chie among hese is he imminen elease o he Second Repo on he S a e o he Wo ld’s Animal Gene ic Resou ces (FAO, 2015b,d) and he Con en ion on Biological Di e si y’s 2020 deadline hal ing he loss o biodi e si y Aichi a ge s. In he con ex o he d ama ic ad ances in ‘omics echnology ha a e expec ed du ing he nex decade, he ield is expec ed o mo e as . Bu s uc u al changes in he li es ock sec o ha will b ing u he e osion du ing his pe iod a e likely o be equally apid. Howe e , his makes i c i ically impo an ha a s a egic app oach is aken o inco po a ing hese echnological ad ances in o eal wo ld FAnGR conse a ion. Such an app oach has been aken in he pas (e.g., wi h he implemen a ion o app o ed mic osa elli e ma ke se s) and, we would a gue, is needed now o ensu e ha p ac ical conse a ion o a m animal ag icul u al biodi e si y is no le behind. The FAnGR communi y he e o e needs o make bes use o new genomic ools, and a he same ime con inue and augmen i s classical pheno yping e o s. Bo h, genomic and pheno ypic ools need o be applied mo e consis en ly, a a much wide scale and o mo e b eeds, o desc ibe, u ilize and conse e he wo ld’s genomic/b eed di e si y o u u e gene a ions. ACKNOWLEDGMENTS The Eu opean Science Founda ion (ESF) GENOMIC— RESOURCES Resea ch Ne wo king P og amme (RNP) was suppo ed by: Fonds zu Fö de ung de wissenscha lichen Fo schung (FWF), FWF Aus ian Science Fund, Aus ia—Fonds Na ional de la Reche che Scien i ique (FNRS), Belgium—Fonds oo We enschappelijk Onde zoek—Vlaande en (FWO), The Resea ch Founda ion—Flande s, Belgium—Nacionalna zaklada za znanos , isoko škols o i ehnologijski az oj Republike H a ske, C oa ian Science Founda ion, Republic o C oa ia—Suomen Aka emia, Bio ie eiden ja ympä is ön u kimuksen oimikun a, Academy o Finland, Resea ch Council o Biosciences and En i onmen , Finland—Deu sche Fo schungsgemeinscha (DFG), Ge man Resea ch Founda ion, Ge many—Nede landse O ganisa ie oo We enschappelijk Onde zoek (NWO), The Ne he lands O ganisa ion o Scien i ic Resea ch, The Ne he lands—No ges Fo sknings åd, The Resea ch Council o No way, No way—Fo sknings åde ö miljö, a eella nä inga och samhällsbyggande, Swedish Council o En i onmen , Ag icul u al Sciences and Spa ial Planning (FORMAS), Sweden—Schweize ische Na ional onds (SNF), Swiss Na ional Science Founda ion, Swi ze land—Bio echnology and Biological Sciences Resea ch Council (BBSRC), Uni ed Kingdom. 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