Quantitative trait loci for fertility traits in Finnish Ayrshire cattle

Gene . Sel. E ol. 40 (2008) 195–214 A ailable online a : c INRA, EDP Sciences, 2008 www.gse-jou nal.o g DOI: 10.1051/gse:2007044 O iginal a icle Quan i a i e ai loci o e ili y ai s in Finnish Ay shi e ca le Nina F. Schulman1∗, Gou am Sahana2, Mogens S. Lund2, Si ja M. Vii ala1, Johanna H. Vilkki1 1MTT Ag i ood Resea ch Finland, Bio echnology and Food Resea ch, 31600 Jokioinen, Finland 2Depa men o Gene ics and Bio echnology, Facul y o Ag icul u al Science, Aa hus Uni e si y, Resea ch Cen e Foulum, 8830 Tjele, Denma k (Recei ed 17 May 2007; accep ed 25 Sep embe 2007) Abs ac – A whole genome scan was ca ied ou o de ec quan i a i e ai loci (QTL) o e ili y ai s in Finnish Ay shi e ca le. The mapping popula ion consis ed o 12 bulls and 493 sons. Es ima ed b eeding alues o days open, e ili y ea men s, ma e nal cal mo - ali y and pa e nal non- e u n a e we e used as pheno ypic da a. In a g anddaugh e design, 171 ma ke s we e yped on all 29 bo ine au osomes. Associa ions be ween ma ke s and ai s we e analysed by mul iple ma ke eg ession. Mul i- ai analyses we e ca ied ou wi h a a i- ance componen based app oach o he ch omosomes and ai combina ions, which we e ob- se ed signi ican in he eg ession me hod. Twen y- wo ch omosome-wise signi ican QTL we e de ec ed. Se e al o he de ec ed QTL a eas we e o e lapping wi h milk p oduc ion QTL p e iously iden i ied in he same popula ion. Mul i- ai QTL analyses we e ca ied ou o es i hese effec s we e due o a pleio opic QTL affec ing e ili y and milk yield ai s o o linked QTL causing he effec s. This dis inc ion could only be made wi h con idence on BTA1 whe e aQTLaffec ing milk yield is linked o a pleio opic QTL affec ing days open and e ili y ea - men s. QTL / e ili y /dai y cow 1. INTRODUCTION High e ili y in cows is economically impo an o dai y a me s. Low e - ili y leads o highe eplacemen cos s, e e ina y cos s, labou cos s and cos s due o educed milk p oduc ion. The p opo ion o e ili y ea men s ep e- sen s 21% [36] o all he e e ina y ea men s in Finland. Also, 20% o he in olun a y culling cases in Finland a e due o e ili y diso de s (Rau ala, pe - sonal communica ion, 2004). ∗Co esponding au ho : nina.schulman@m . i A icle published by EDP Sciences and a ailable a h p://www.gse-jou nal.o g o h p://dx.doi.o g/10.1051/gse:2007044 196 N.F. Schulman e al. Fe ili y ai s ha e a low he i abili y and a e o en difficul o measu e [31]. Gene ic p og ess by adi ional b eeding can he e o e be slow and he neg- a i e co ela ions wi h p oduc ion ai s a e o special conce n [34]. Pösö and Män ysaa i [34] ha e epo ed ha a gene ic imp o emen o 500 kg milk yield would inc ease cases o o ula o y diso de s by 1.7%-uni s and days open by 4.2 days. These a e ai s o which ma ke -assis ed selec ion could inc ease gene ic p og ess compa ed o adi ional b eeding schemes [25,38]. A emp s ha e been made o map loci affec ing e ili y. QTL ha e been de- ec ed o o ula ion a e [4], winning [26], days open [39], non- e u n a e and s illbi h [24], e ili y ea men s [15], and p egnancy a e [2]. In Finland, mapping e ili y ai s is easible because he e is a good heal h da a eco d- ing sys em wi h a da abase main ained by he Ag icul u al Da a P ocessing Cen e L d. Se e al s udies ha e ound un a ou able associa ions be ween milk p oduc- ion ai s and e ili y ai s [23, 34, 37]. Cows wi h high milk yield eco ds end o ha e poo e e ili y pe o mances han cows wi h mode a e o low milk p oduc ion. Selec ion o high milk yield has led o longe in e als be ween cal ing and he ollowing p egnancy and an inc ease in e ili y diso de s. In o de o use ma ke in o ma ion o selec o be e e ili y wi hou comp o- mising imp o emen in milk p oduc ion, mo e knowledge on he ch omoso- mal egions affec ing bo h milk and e ili y ai s and he unde lying genes is needed. Milk p oduc ion ai s and e ili y ai s a e co ela ed gene ically. This gene ic co ela ion may be due o pleio opic QTL affec ing bo h ai s simul aneously and/o o linked QTL each affec ing one ai . Fo effec i e ma ke -assis ed selec ion, i is necessa y o dis inguish be ween a pleio opic QTL and a linked QTL o a oid undesi able co ela ed esponses. The s an- da d way o deciding how many QTL (ma ginal effec s) and hei in e ac ion effec s should appea in he inal model elies on compa ing se e al models, e.g. single- ai analysis wi h one o mul iple QTL models ollowed by mul i- ai analysis wi h pleio opic o linked QTL models. The e a e wo limi a ions o his app oach: i s , i allows he compa ison o nes ed models only; second, i is no clea how o adjus he signi icance h eshold o each consecu i e es [5]. Akaike in o ma ion c i e ion (AIC) [1] o Schwa z Bayesian in o ma- ion c i e ion (BIC) [41] a e wo c i e ia ha do no equi e ha he compa ed models be nes ed and hey ha e o en been employed o choose ma ke co a i- a es o mul iple QTL mapping [16, 17] o o di ec ly es ima e QTL numbe e.g. [3, 5, 7, 30, 42]. Piepho and Gauch [33] ha e in es iga ed model selec- ion c i e ia ia simula ion. Thei esul s sugges ha ou o he conside ed Fe ili y QTL in Finnish Ay shi e 197 c i e ia BIC has he bes p ope ies and can be used o he es ima ion o he numbe o QTL wi h main effec s. The objec i es o his s udy we e (i) o use he Finnish g anddaugh e de- sign da a o map QTL o e ili y ai s (days open, e ili y ea men s, pa- e nal non- e u n a e, and cal mo ali y in he Finnish Ay shi e popula ion); (ii) o dis inguish be ween pleio opy and linked QTL when a egion is a - ec ing mo e han one e ili y ai o a leas one e ili y ai and milk ai iden i ied p e iously by Vii ala e al. [46]. 2. MATERIAL AND METHODS 2.1. T ai s and popula ion Days open (DO) is calcula ed as he numbe o days om cal ing o he ol- lowing p egnancy. Fe ili y ea men s (FT) include in o ma ion abou e ili y ea men s done by a e e ina ian wi hin 150 days a e cal ing and in o ma- ion abou culling due o e ili y p oblems. Non- e u n a e (NRR) indica es he abili y o a bull o make cows p egnan . I s e alua ion is based on he in- semina ion o he bull’s semen o a andom se o cows and in his s udy, is measu ed as he non- e u n a e wi hin 60 days om insemina ion wi h he i s 500 insemina ions o a bull included in he da a. Cal mo ali y (CM) is measu ed he e as a ai o he si e o he cow. I indica es he mo ali y a bi h o he offsp ing o he daugh e s. The esponse a iables used in QTL mapping we e b eeding alues ob ained om he Finnish Animal B eeding Associa ion mainly om he e alua ion ca ied ou in au umn 2000. Fo NRR, he b eeding alues om he e alua ion ca ied ou in sp ing 1996 we e used because he e was no enough da a o he six oldes g andsi es in he yea 2000 e alua ion o NRR. B eeding alues o DO we e es ima ed using a epea abili y animal model and o FT a epea abili y si e model. Reco ds om he i s h ee lac a ions we e used. All bulls in he mapping popula ion had daugh e eco ds om all h ee lac a ions. Fo CM a si e-g andsi e model was used. CM and FT we e eco ded as bina y ai s. The he i abili y es ima es used o calcula ing he b eeding alues we e 0.05 o DO, 0.01 o FT, 0.03 o CM, and 0.03 o NRR. The milk yield ai s used o pleio opic and linked QTL analyses we e he ollowing: milk yield 1s lac a ion (MY), p o ein yield 1s lac a ion (PY), a yield 1s lac a ion (FY). Daugh e yield de ia ions (DYD) o igina ed om a es day animal model. A g anddaugh e design was used o QTL mapping. Twel e Finnish Ay shi e hal -sib amilies we e geno yped. Only ele en o hem could be used 198 N.F. Schulman e al. o he analysis o CM because he smalles amily did no ha e enough sons wi h daugh e eco ds o his ai . The numbe o geno yped sons pe si e anged om 21 o 82 wi h an a e age o 41 sons. The o al numbe o sons in he popula ion was 493. The a e age numbe o daugh e eco ds pe bull was 496 o DO, 468 o FT, and 841 o CM. 2.2. Ma ke s and geno ypes Ma ke s we e geno yped on all 29 bo ine au osomes. All a ailable sons o he chosen bull si es we e yped. A o al o 169 mic osa elli es and wo candida e gene SNP we e used. Ou o hese, 21 mic osa elli es we e new compa ed o hose epo ed in p e ious s udies wi h he Finnish g anddaugh- e design [40, 46]. Thus, ele en linkage maps we e ecalcula ed. The link- age maps a e a ailable a h p://www.m . i/julkaisu /ca leq l. The numbe o ma ke s pe ch omosome a ied om 2 o 14. The a e age spacing be ween ma ke s was 19 cM. The o al leng h o he analysed genome was 2618 cM. ANIMAP [12] o CRIMAP [13] we e used o cons uc he linkage maps. The me hods o DNA ex ac ion, PCR eac ion p o ocols, and elec opho esis ha e been desc ibed in p e ious s udies [10, 47]. 2.3. S a is ical analysis QTL analyses consis ed o he ollowing s eps: (1) a genome scan was ca ied ou using mul iple linea eg ession o ou e ili y ela ed ai s; (2) he signi ican QTL de ec ed om (1) and milk p oduc ion QTL de ec ed by Vii ala e al. [46] ha o e lapped wi h he e ili y QTL we e eanalysed wi h he a iance componen me hod using a single- ai model (STVC); (3) mul i- ai pleio opic (MTP) and linked (MTL) QTL models we e analysed when QTL o wo e ili y ai s o one e ili y ai and one milk yield ai [46] we e de ec ed on he same ch omosome. 2.3.1. Reg ession me hod Associa ions be ween ma ke s and ai s we e analysed using a mul iple ma ke eg ession app oach [22]. The model used was he ollowing: yij =ai+ bixij +eij,whe ey ij is he b eeding alue o bull j, who belongs o amily i, aiis he polygenic effec o hal -sib amily i, biis he allele subs i u ion e - ec o a QTL wi hin amily i, xij is he condi ional p obabili y o bull j Fe ili y QTL in Finnish Ay shi e 199 o inhe i ing he i s haplo ype om si e i, and eij is he esidual. Signi i- cance h esholds and P- alues o he F-s a is ic, we e ob ained by pe mu a- ion, which was epea ed 10 000 imes o each ai and ch omosome sep- a a ely [8]. Genome wise P- alues we e ob ained by Bon e oni co ec ion Pgenome =1−(1 −Pch omosome)29, whe e 29 is he o al numbe o ch omo- somes analysed. A wo-QTL model was i ed in he eg ession analysis o hose ch omo- somes ha had mo e han h ee in o ma i e ma ke s i one signi ican QTL had been de ec ed and i he es ima ed QTL posi ions in he indi idual am- ilies indica ed wo diffe en posi ions [44, 45]. Wi h he wo-QTL model, he pe mu a ions we e done o es wo QTL s. no QTL. I his esul exceeded he ch omosome-wise signi icance h eshold o 5%, he P- alue o wo QTL s. one QTL was ob ained om a s anda d F able. The deg ees o eedom o he F s a is ic we e he numbe o g andsi es as he nume a o and o al numbe o offsp ing minus h ee imes he numbe o g andsi es as he denomina o . 2.3.2. Va iance componen me hod Single- and mul i- ai QTL mapping based on he a iance componen me hod was ca ied ou using he me hod desc ibed by Lund e al. [27]. The ai s we e modelled using he ollowing linea mixed model wi h nqnumbe o QTL: y=µ+Zu + nq  i=1 Wqi+e, whe e yis a ec o o b eeding alues o DYD eco ded on ai s o each geno yped son, µis a ec o o o e all ai means, Zand Wa e incidence ma ices, uis a ec o o andom addi i e polygenic effec esul s om a com- bined effec o backg ound genes, qiis a ec o o he effec s o he i h QTL, and eis a ec o o andom esidual effec s. The andom a iables u,qiand e a e assumed o be mul i a ia e no mally dis ibu ed and mu ually unco ela ed. Fo de ails o he me hod see Lund e al. [27]. The a iance componen s we e es ima ed using he a e age in o ma ion es ic ed maximum likelihood algo i hm [18] implemen ed in he so wa e package DMU [29]. The es ic ed likelihood was maximised wi h espec o he a iance componen s associa ed wi h he andom effec s in he model. Maximising a sequence o es ic ed likelihoods o e a g id o speci ic posi- ions yields a p o ile o he es ic ed likelihood o he QTL posi ion. The in e al o QTL was es ima ed by one-LOD suppo [28]. 200 N.F. Schulman e al. 2.3.2.1. IBD ma ices The elemen s in he IBD ma ix a e a unc ion o he ma ke da a and he po- si ion (p) o a pu a i e QTL on he ch omosome. He e we used he mos likely ma ke linkage phase in he si e and compu ed he IBD ma ix using a ecu - si e algo i hm [48]. The IBD ma ices we e compu ed o e e y 4 cM along he ch omosomes and used in he subsequen a iance componen es ima ion p ocedu e. 2.3.2.2. Tes s a is ics Hypo hesis es s o he p esence o QTL we e based on he asymp o ic dis- ibu ion o he likelihood a io es (LRT) s a is ic, LRT =–2ln(L educed −L ull), whe e L educed and L ull we e he maximised likelihoods unde he educed model and ull model, espec i ely. The educed model always excluded he QTL effec o he ch omosome being analysed. The wo-QTL models we e compa ed wi h one-QTL (null) models. Th esholds we e calcula ed using he me hod p esen ed by Piepho [32]. 2.3.2.3. Model selec ion be ween pleio opic and linked-QTL models Since he pleio opic and he linked-QTL models a e no nes ed, he Bayesian In o ma ion C i e ion (BIC) [20, 41] was used o e alua e which model was a ou ed. The wo models in he p esen s udy en ail he same numbe o pa ame e s and consequen ly he BIC simpli ies o 2logp(y|ˆ θlinkageMlinkage) p(y|ˆ θpleio opyMpleio opy). I he wo models a e assumed equally likely ap i- o i, he esul s using his c i e ia a e an app oxima ion o he pos e io p oba- bili y o he pleio opic model ela i e o he pos e io p obabili y o he linked QTL model (Bayes ac o ). We used he BIC calib a ion able by Ra e y [35] o in e p e ing BIC es ima es. A BIC sco e o ⩾6 (model M1 s. M2) in- dica ed s ong e idence o M1 o e M2. Ano he less o mal c i e ion used o indica e which model is mo e likely, is he es ima ed co ela ion be ween QTL effec s on he wo ai s ( Q12) om he pleio opic model. The a ionale behind using Q12 is ha i he wo ai s a e unde he in luence o a biallelic pleio opic QTL he ue alue o Q12 will be one. Fe ili y QTL in Finnish Ay shi e 201 3. RESULTS 3.1. Days open In he single- ai eg ession analysis, QTL o DO we e de ec ed on BTA1, 2, 5, 12, 20, 25, and 29 a ch omosome-wise 5% signi icance (Tab. I). The single- ai model wi h a iance componen analysis (STVC) con i ms QTL on BTA1 and 12 in he same egion o he ch omosomes (Tab. I). The wo- QTL model wi h eg ession was i ed o BTA1 and 2. No suppo was ound o his model o ei he ch omosome. In he analysis wi hin amilies he e we e wo o i e amilies wi h ch omosome-wise signi ican F- alues pe ch o- mosome. The posi ions o he highes F- alues on he ch omosomes we e no consis en be ween amilies. The es ima ed allele subs i u ion effec s in hese amilies anged om 0.7 o 1.5 s anda d de ia ions o EBV, which means 5.2 o 11.1 days. 3.2. Fe ili y ea men s Wi h he eg ession analysis, QTL we e de ec ed on BTA1, 10, 15, 19, and 25 a ch omosome-wise 5% signi icance and on BTA5 and 14 a ch omosome- wise 1% signi icance (Tab. I). The STVC analysis con i ms he QTL o FT on BTA1. The wo-QTL model using eg ession analysis was signi ican o BTA1, 5, and 14 (Tab. II). The s onges e idence o wo QTL was on BTA14. The e we e one o ou amilies wi h ch omosome-wise signi ican F- alues in he analysis wi hin amilies. The posi ions o he highes F- alues diffe ed be- ween amilies. The allele subs i u ion effec s anged om 0.6 o 2.2 s anda d de ia ions o EBV o 0.62% o 2.22% o ea men s. On BTA1 and BTA25 he QTL posi ions in he ac oss amilies analysis o DO and FT we e o e lapping. Fo bo h ch omosomes he QTL posi ions we e a he end o he ch omosome, on BTA1 close o ma ke BMS4014 and on BTA25 close o ma ke AF5 (Figs. 1 and 2). 3.3. Cal mo ali y In he single ai eg ession analysis, QTL o CM we e de ec ed on BTA4, 6, 11, 15, 18, and 23 a 5% ch omosome-wise signi icance (Tab. I). The STVC analyses did no con i m any o he QTL o CM, howe e , he QTL on BTA4 and 15 we e close o signi icance. The wo-QTL model using eg ession was no suppo ed o any o he ch omosomes. In he analysis wi hin amilies 202 N.F. Schulman e al. BTA1 0 0.5 1 1.5 2 2.5 3 3.5 1 163146617691106121136151 cM F- alue Figu e 1. P o iles o linea eg ession es s a is ics o BTA1 om single ai analysis ac oss amilies. Quan i a i e ai loci we e de ec ed o days open and e ili y ea - men s . The uppe ho izon al line indica es he ch omosome-wise 5% h eshold le el o e ili y ea men s and he lowe dashed line he ch omosome-wise 5% h eshold le el o days open. BTA25 0 0.5 1 1.5 2 2.5 3 3.5 4 1 4 7 10131619222528313437404346495254 cM F- alue Figu e 2. P o iles o linea eg ession es s a is ics o BTA25 om single ai anal- ysis ac oss amilies. Quan i a i e ai loci we e de ec ed o days open and e ili y ea men s . The 5% h eshold le els o he ai s a e shown. The uppe ho izon al line indica es he ch omosome-wise 5% h eshold le el o e ili y ea men s and he lowe dashed line he ch omosome-wise 5% h eshold le el o days open. Fe ili y QTL in Finnish Ay shi e 203 Table I. Quan i a i e ai loci o days open, e ili y ea men s, cal mo ali y and non- e u n a e wi h eg ession and a iance componen me hods in Finnish Ay shi e ca le. T ai BTA1Reg ession me hod Va iance componen me hod Pos.2(cM) F- alue Pos. (cM) LRT3 Days open 1 146 2.75∗∗ 144 11.29∗∗ 2 2 2.86∗∗ 0.1 3.26 5 108 2.86∗∗ 107 4.29 12 47 2.34∗48 8.49∗ 20 1 2.44∗25.80 25 47 2.93∗∗ 45 5.19 29 4 2.27∗45 4.90 Fe ili y 1 151 3.09∗148 9.75∗ ea men s 5 113 3.94∗∗ 84 3.83 10 145 2.99∗25.83 14 67 3.46∗∗ 50 1.37 15 1 3.30∗120 4.09 19 1 3.19∗11.78 25 54 3.60∗∗ –<1.0 Cal 4 17 2.36∗16.60 mo ali y 6 93 2.71∗85 3.9 11 29 2.09∗16 2.75 15 115 2.08∗120 6.33 18 1 2.24∗–<1.0 23 3 2.02∗12.05 Non- e u n 10 68 2.06∗144 3.54 a e 14 29 2.14∗30 2.85 1BTA =Bos au us ch omosome. 2Pos. =posi ion. 3LRT =likelihood a io es s a is ics. ∗P<0.05; ∗∗ P<0.01. he e we e wo o ou amilies wi h ch omosome-wise signi ican F- alues pe ch omosome. Fo BTA15, h ee amilies had hei highes F- alues close o ma ke MGTG13B. Fo BTA18, wo amilies had hei highes F- alues a BMS1355 and wo be ween ma ke s BMS1355 and BMS2213. On he o he ch omosomes wi h signi ican QTL in he ac oss amilies analysis, he posi- ions o he highes F- alues we e no consis en be ween amilies. The allele subs i u ion effec s o he de ec ed QTL anged om 0.5 o 2.2 s anda d de i- a ions o EBV, which is 0.45% o 2.0% o CM. 210 N.F. Schulman e al. The posi ion o he QTL on BTA10 [24] was be ween ma ke s TGLA378 and TGLA102, which is close o ou inding nea he ma ke ILSTS53. When compa ing he e ili y QTL wi h he posi ions o he milk ai QTL de ec ed in an ea lie s udy in he same amilies [46], se e al milk and e ili y QTL we e ound on he same ch omosomes. Fo example, on BTA25, whe e QTL we e de ec ed o DO and FT a he end o he ch omosome, QTL o milk yield and p o ein yield we e also de ec ed. Fu he mo e, BTA1, 2, 5, and 12 ha bou QTL o milk and e ili y on app oxima ely he same ch omosome segmen s acco ding o he eg ession based linkage analysis. Mul i- ai QTL analyses we e ca ied ou on eigh ch omosomes, which ha bou QTL o mo e han one e ili y ai o a leas one e ili y ela ed ai and one milk p oduc ion ai iden i ied ea lie by Vii ala e al. [46] in he same popula ion. We selec ed he ch omosomes based on he signi icance o he QTL in he eg ession analysis. Though some o hese QTL we e no sig- ni ican in he single- ai VC me hod, we did no pu his as a p econdi ion o selec ing he ch omosome and ai combina ions. This was done as a mul i- ai analysis o a pleio opic QTL because i has highe s a is ical powe o de ec ion and a highe p ecision o he es ima ed map posi ion compa ed o analysing he ai s indi idually [19,21,43]. Sø ensen e al. [43] obse ed ha his is especially ue when a second co ela ed ai wi h highe he i abili y (e.g. milk yield ai s in ou s udy) is used oge he wi h a low he i abili y ai (e.g. e ili y ai s in ou s udy). Besides, a majo i y o he QTL iden i- ied by eg ession, which did no exceed he signi icance h eshold in STVC analysis, had sugges i e e idence o QTL seg ega ion in he same egion o he ch omosome when analysed wi h STVC. The e o e, we kep a libe al en- y le el o he QTL o be included in he mul i- ai analysis. Ou esul s suppo he ea lie indings o Jiang and Zeng [19], Kno and Haley [21] and Sø ensen e al. [43] ha show ha mul i- ai analyses ha e mo e powe in de ec ing QTL compa ed o single- ai analyses. Mul i- ai QTL analyses we e able o dis inguish pleio opic QTL om linked QTL only on BTA1 and no on he o he ch omosomes. The esul s also indica ed linked QTL on BTA5, 12, 14 and 15 o e ili y ela ed ai s and milk p oduc ion ai s, bu i was no possible o p ecisely selec he linked model o e he pleio opic model o ice e sa. The QTL in e als (one-LOD suppo ) on a single ch omosome affec ing mo e han one ai we e la ge and o e lapping. Also, he seg ega ing amilies had QTL peaks sp ead o e a conside ably la ge egion o he ch omosome. The ma ke den- si y used in he genome scan was spa se (a e age ma ke spacing 19 cM) and inc easing ma ke densi y may help in educing he QTL in e al in linkage Fe ili y QTL in Finnish Ay shi e 211 mapping especially o dis inguish pleio opic/linked QTL. The ai s show a i- able amoun s o gene ic co ela ion. A signi ican QTL o a gi en ai migh be non-signi ican o a highly co ela ed ai bu s ill ha e an effec on i [11]. This makes he sepa a ion be ween a QTL ha ing a pleio opic effec on wo ai s and a QTL affec ing only one ai and showing an effec on he o he ai due o a linked QTL, difficul . 5. CONCLUSIONS Fou ai s ela ed o bo ine e ili y we e analysed in a QTL mapping s udy. A o al o 22 ch omosome-wise signi ican QTL we e sugges ed in eg ession analysis and h ee we e con i med wi h he single ai a iance componen me hod. Only ew o he de ec ed QTL ha e been epo ed in ea lie s ud- ies and many o he QTL o he p e ious s udies we e no suppo ed in he p esen s udy. This could be due o a low powe o de ec ion ela ed o he low he i abili y and difficul y o adequa ely measu e hese ai s. Some o he e - ili y ai QTL a e closely linked o milk p oduc ion QTL o he QTL show pleio opic effec s on milk p oduc ion and e ili y ai s. A dense ma ke map, la ge popula ion and linkage disequilib ium based mapping may be needed o dis inguish wo-linked QTL om a pleio opic QTL. ACKNOWLEDGEMENTS We would like o hank Anneli Vi a, Jonna Roi o and Tiina Jaakkola o he labo a o y wo k, Jukka Pösö om he Finnish Animal B eeding Associa ion o p o iding he EBV o he bulls, and he AI s a ions o semen samples. The esea ch was pa ly unded by he Minis y o Ag icul u e and Fo es y o Finland (Resea ch g an 4750/501/2004) and he Finnish Animal B eeding Associa ion. REFERENCES [1] Akaike H., A new look a he s a is ical model iden i ica ion, IEEE T ans. Au oma . Con . 19 (1974) 716–723. [2] Ashwell M.S., Heyen D.W., Sons ega d T.S., an Tassell C.P., Da Y., VanRaden P.M., Ron M., Welle J.I., Lewin H.A., De ec ion o quan i a i e ai loci affec - ing milk p oduc ion, heal h, and ep oduc i e ai s in Hols ein ca le, J. Dai y Sci. 87 (2004) 468–475. 212 N.F. Schulman e al. 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