Disease Resis ance in A lan ic Salmon (
Salmo sala
):
Coin ec ion o he In acellula Bac e ial Pa hogen
Pisci icke sia salmonis
and he Sea Louse
Caligus
oge c esseyi
Jean Paul Lho en e
1
, Jose
´A. Galla do
2
*, Bea iz Villanue a
3
, Ma ı
´a J. Ca aban
˜o
3
, Robe o Nei a
1,4
1Aquainno o S.A, Pue o Mon , Chile, 2Pon i icia Uni e sidad Ca o
´lica de Valpa aı
´so, Valpa aı
´so, Chile, 3Depa amen o de Mejo a Gene
´ ica Animal, INIA, Mad id, Spain,
4Depa amen o de P oduccio
´n Animal, Facul ad de Ciencias Ag ono
´micas, Uni e sidad de Chile, San iago, Chile
Abs ac
Backg ound:
Na u ally occu ing coin ec ions o pa hogens ha e been epo ed in salmonids, bu hei consequences on
disease esis ance a e unclea . We hypo hesized ha 1) coin ec ion o Caligus oge c esseyi educes he esis ance o A lan ic
salmon o Pisci icke sia salmonis; and 2) coin ec ion esis ance is a he i able ai ha does no co ela e wi h esis ance o a
single in ec ion.
Me hodology:
In o al, 1,634 pedig eed A lan ic salmon we e exposed o a single in ec ion (SI) o P. salmonis (p ima y
pa hogen) o coin ec ion wi h C. oge c esseyi (seconda y pa hogen). Low and high le el o coin ec ion we e e alua ed
(LC = 44 copepodi es pe ish; HC = 88 copepodi es pe ish). Su i al and quan i a i e gene ic analyses we e pe o med o
de e mine he esis ance o he single in ec ion and coin ec ions.
Main Findings:
C. oge c esseyi signi ican ly inc eased he mo ali y in ish in ec ed wi h P. salmonis (SI mo ali y = 251/545;
LC mo ali y = 544/544 and HC mo ali y = 545/545). He i abili y es ima es o esis ance o P. salmonis we e simila and o
medium magni ude in all ea men s (h
2SI
= 0.2360.07; h
2LC
= 0.1760.08; h
2HC
= 0.2460.07). A la ge and signi ican gene ic
co ela ion wi h ega d o esis ance was obse ed be ween coin ec ion ea men s (
g
LC-HC = 0.9960.01) bu no be ween
he single and coin ec ion ea men s (
g
SI-LC = 20.1460.33;
g
SI-HC = 0.3260.34).
Conclusions/Signi icance:
C. oge c esseyi, as a seconda y pa hogen, educes he esis ance o A lan ic salmon o he
pa hogen P. salmonis. Resis ance o coin ec ion o Pisci icke sia salmonis and Caligus oge c esseyi in A lan ic salmon is a
he i able ai . The absence o a gene ic co ela ion be ween esis ance o a single in ec ion and esis ance o coin ec ion
indica es ha di e en genes con ol hese p ocesses. Coin ec ion o di e en pa hogens and esis ance o coin ec ion
needs o be conside ed in u u e esea ch on salmon a ming, selec i e b eeding and conse a ion.
Ci a ion: Lho en e JP, Galla do JA, Villanue a B, Ca aban
˜o MJ, Nei a R (2014) Disease Resis ance in A lan ic Salmon (Salmo sala ): Coin ec ion o he In acellula
Bac e ial Pa hogen Pisci icke sia salmonis and he Sea Louse Caligus oge c esseyi. PLoS ONE 9(4): e95397. doi:10.1371/jou nal.pone.0095397
Edi o : J. S ephen Dumle , The Johns Hopkins Uni e si y School o Medicine, Uni ed S a es o Ame ica
Recei ed Janua y 9, 2014; Accep ed Ma ch 25, 2014; Published Ap il 15, 2014
Copy igh : ß2014 Lho en e e al. This is an open-access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion License, which pe mi s
un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal au ho and sou ce a e c edi ed.
Funding: This s udy was inanced by INNOVA-CHILE o CORFO h ough he p ojec s: 1) Conso cio emp esa ial de gene
´ ica y desa ollo bio ecnolo
´gico pa a la
indus ia salmone a (Nu206-5047), and 2) Desa ollo de una nue a me odologı
´a pa a la iden i icacio
´n y seleccio
´n de salmo
´nidos gene
´ icamen e esis en es al
ec opa a
´si o Caligus oge c esseyi (07CN13PBT-61). This s udy is a collabo a i e wo k o di e en ins i u ions belonging o ‘‘Red de gene
´ ica e inmunologı
´a pa a el
con ol de pa o
´genos en Acuicul u a’’ (RED CYTED Nu11RT0420). BV ecei ed unding om he Minis e io de Economı
´a y Compe i i idad, Spain (p ojec CGL2012-
39861-C02-02). The unde s had no ole in s udy design, da a collec ion and analysis, decision o publish, o p epa a ion o he manusc ip .
Compe ing In e es s: Jean Paul Lho en e and Robe o Nei a we e employed in AQUAINNOVO when his esea ch was pe o med. This does no al e he
au ho s’ adhe ence o all he PLOS ONE policies on sha ing da a and ma e ials.
* E-mail: [email p o ec ed]
In oduc ion
Na u ally occu ing coin ec ions o pa hogens ha e been
epo ed in a ious salmonid species [1], [2]. Howe e , he
consequences o o e all disease esis ance emain unclea . Mos
s udies ha e shown ha p esence o a p ima y pa hogen educes
he esis ance esponse o a seconda y pa hogen. Fo example, in
ainbow ou , p ima y in es a ion o he pa asi e Myxobolus
ce eb alis supp esses he immune sys em, inc easing mo ali y
associa ed wi h a seconda y in ec ion by Ye sinia ucke i [3].
Simila ly, A lan ic salmon in ec ed wi h IPNV show signi ican ly
inc eased mo ali y as smol s when exposed o Fu unculosis,
Vib iosis and ISA [4], [5]. Con e sely, se e al s udies ha e
shown ha coin ec ion does no necessa ily inc ease mo ali y. Fo
example, some s udies on ainbow and b own ou showed ha
IPNV educed he in ec ion capaci y o he hema opoie ic nec osis
i us (IHNV) and ha he mo ali y o ish in ec ed wi h bo h
i uses was signi ican ly lowe han ha obse ed in single
challenges wi h each pa hogen [6], [7], [8], [9]. Fu he mo e,
acu e coin ec ion o IPN and ISA in A lan ic salmon signi ican ly
educed mo ali y compa ed wi h a single in ec ion by ISA [4].
Sea lice a e among he mos impo an sani a y p oblems in he
global salmon aquacul u e indus y [10], u he hey ha e been
PLOS ONE | www.plosone.o g 1 Ap il 2014 | Volume 9 | Issue 4 | e95397
linked o wild salmon and ou popula ion declines a ound he
wo ld [11], [12], [13]. Salmonid in es a ion by sea lice may be
associa ed wi h le hal o sub-le hal e ec s [14], [15], [16]. Sub-
le hal e ec s may include s ess [17], [18], loss o appe i e,
dep ession o he immune sys em and skin damage [19], [20], and
he e o e, i can con ibu e o inc eased suscep ibili y o o he
diseases [21], [22]. In ag eemen wi h his hypo hesis, Mus a a
e al. [22] epo ed ha A lan ic salmon in ec ed wi h he sea louse
Lepeoph hei us salmonis showed inc eased suscep ibili y o a mic o-
spo idian pa asi e (Loma salmonae). Recen ly, Nowak e al. [23],
Bus os e al. [24] and Valdes-Donoso e al. [25] sugges ed, based
on ield s udies on A lan ic salmon, ha sea lice a ec disease
esis ance o he amoeba Neopa amoeba pe u ans and o ISA .
In Chile, caligidosis caused by Caligus oge c esseyi and pisci ick-
e siosis caused by Pisci icke sia salmonis ha e his o ically been he
mos impo an heal h p oblems in he salmon indus y in he
g ow h-ou p oduc ion phase [26], [27], [28], [10]. C. oge c esseyi is
he only sea louse ha a ec s he Chilean salmon indus y [29],
and annual losses a ibu ed o his pa asi e a e es ima ed a mo e
han $178 million US [27], [10]. P. salmonis, an in acellula
bac e ium, was desc ibed in Chile a he end o he 1980s in he X
egion [30], [31], [32] and was ini ially ound o be s ongly
associa ed wi h A lan ic salmon. I has now ex ended o o he
salmonid species a med in Chile [33], p oducing mo ali y a es
o up o 50% in ish in he sea g owing s age, wi h mone a y losses
exceeding $100 million US pe yea [28]. Fu he mo e, P. salmonis
has been epo ed in di e en coun ies and can in ec ainbow
ou (Onco hynchus mykiss), che y salmon (Onco hynchus masou),
chinook salmon (Onco hynchus shawy scha) and pink salmon
(Onco hynchus go buscha) [34].
Resis ance o A lan ic salmon o C. oge c esseyi and P. salmonis has
ecen ly been s udied in single-in ec ion challenges in labo a o y
condi ions by Yan˜ez e al. [35] and Lho en e e al. [36]. Lho en e
e al. [36] epo ed he i abili y o esis ance o A lan ic salmon o
he sea louse C. oge c esseyi o low (0.03–0.06) and medium (0.22–
0.34) magni udes o he mobile and sessile s ages o he pa asi e,
espec i ely. O he s udies pe o med on di e en sea lice species
con i med ha A lan ic salmon ha e a he i able de ensi e
mechanism agains Lepeoph hei us salmonis [37], [38], [39] and
Caligus elonga us [40]. Addi ionally, i has been shown ha bo h wild
and a med A lan ic salmon ha e a he i able de ensi e mechanism
agains a ious bac e ia [41], [42], [43], [44], including P. salmonis
[45]. Fo ins ance, Yan˜ez e al. [35] epo ed he i abili y o
esis ance o A lan ic salmon o P. salmonis anging om 0.11 o
0.41.
In his s udy, we hypo hesized ha coin ec ion wi h he sea louse
C. oge c esseyi educes he esis ance o A lan ic salmon o P.
salmonis because o he well-documen ed s ess and dep ession o
he immune sys em p oduced by sea lice in ec ion in salmonids.
Addi ionally, we hypo hesized ha coin ec ion esis ance is a
he i able ai ha does no co ela e wi h esis ance o a single
in ec ion o P. salmonis because salmonid de ense mechanisms
agains bac e ia and pa asi es a e subs an ially di e en [46]. We
p esen expe imen al e idence suppo ing bo h hypo heses o he
in e ac ion be ween A lan ic salmon, P. salmonis and C. oge c esseyi.
Ma e ials and Me hods
E hics S a emen
This s udy was ca ied ou in in acco dance wi h he guide o
he ca e and use o expe imen al animals o he Canadian Council
on Animal Ca e. The p o ocol was app o ed by he Bioe hical
commi ee o he Pon i icia Uni e sidad Ca o´lica de Valpa aı
´so
(Nu10/2013). The animals we e anaes he ized wi h benzocaine
p io o he a ious handling p ocesses and ma king. Eu hanasia
was pe o med using an o e dose o anes hesia. All e o s we e
made o p o ide he bes g owing condi ions and o minimize
su e ing.
Fish
In o al, 1,634 A lan ic salmon smol ish o 103 g a e age body
weigh om 15 ull-sib amilies (co esponding o se en pa e nal
hal -sib amilies) o he AquaChile Gene ic P og am we e a ailable
o his s udy. The amilies o igina ed om a nes ed ma ing design
(15 emales and se en males), in which one male e ilized he eggs
o a leas wo emales. Eggs om each amily we e p oduced
du ing he spawning season o 2009. The ish we e ed egula ly
wi h a comme cial die and indi idually agged in Ap il 2010 a an
a e age weigh o 5 g (SD = 8.0 g). Then, hey we e ans e ed as
smol s in Feb ua y 2011 o he Aquad ice S.A. expe imen al
s a ion loca ed a he Quillaipe sec o o Pue o Mon (Chile). A
heal h check by PCR was pe o med p io o ans e o e i y ha
he ish we e ee o i al (IPN and ISA ) and bac e ial pa hogens
(P. salmonis,Renibac e ium salmonina um,Vib io sp and Fla obac e ia sp).
A he expe imen al s a ion, he ish unde wen a h ee-week
acclima ion pe iod unde seawa e condi ions (salini y o 33% and
a empe a u e o 12uC).
Expe imen al Design
The ish we e exposed o h ee di e en in ec ion scena ios wi h
h ee eplica es ( anks) o simula e single in ec ion by P. salmonis
and coin ec ion by P. salmonis wi h wo di e en le els o in ec ion
p essu e o he pa asi e C. oge c esseyi. In all coin ec ion’s
expe imen s P. salmonis was used as p ima y pa hogen and C.
oge c essyi was used as a seconda y pa hogen. Bo h le els o
in ec ion p essu e we e es ablished using in o ma ion om
p e ious expe imen s [47] and se up o expe imen al ish size o
ensu e success ul bu di e en ial se lemen be ween ea men s
and no mo ali y associa ed o single sea lice in ec ion [47,48]. Sea
lice used o p oduce copepodi es we e pa hogen ee (P. salmonis
and ISA ). Fish om he 15 ull-sib amilies we e equally
dis ibu ed in nine anks o 0.72 m
3
such ha he same numbe
o ish pe amily was used in each o he ollowing ea men s:
a) Single in ec ion (SI). The ish we e in ec ed wi h P.
salmonis using a cohabi a ion challenge es in an en i onmen ee
o C. oge c esseyi.
b) Low p essu e o coin ec ion (LC). The ish we e in ec ed
wi h P. salmonis using a cohabi a ion challenge es and hen
in es ed wi h C. oge c esseyi using a low in es a ion p essu e o 44
copepodi es pe ish.
c) High p essu e o coin ec ion (HC). The ish we e
in ec ed wi h P. salmonis using a cohabi a ion challenge es and
hen in es ed wi h C. oge c esseyi using a high in es a ion p essu e o
88 copepodi es pe ish.
The cohabi a ion me hod used o he p ima y in ec ion wi h P.
salmonis p oduces a na u al in es a ion and educes he manipu-
la ion o expe imen al ish in compa ison wi h in a-pe i oneal
injec ion. A he beginning o he challenge wi h P. salmonis (day
ze o), 78 ish wi h unknown pedig ee, e e ed o he e as in ec i e
ish, we e in ec ed by in a-pe i oneal injec ion. A olume o
0.2 ml/ ish (a 10
6,2
TCID/ml) o a i ulen s ain o P. salmonis,
isola ed om A lan ic salmon and comme cially a ailable om
ADL-Diagnos ic L da., was injec ed o each in ec i e ish. The
in ec i e ish we e hen placed in o cohabi a ion wi h agged ish o
each an abundance o 260 ish app. pe ank and a densi y o
42 kg/m
3
. The mo ali y o he in ec i e ish was 100% a 30 days
pos -in ec ion, hose ish we e no included in ou e alua ion o
esis ance. Resis ance o P. salmonis was measu ed as a mo ali y
Resis ance o Coin ec ion in A lan ic Salmon
PLOS ONE | www.plosone.o g 2 Ap il 2014 | Volume 9 | Issue 4 | e95397
ai (dead/ali e). The sexes, ini ial weigh s and inal weigh s o all
cohabi an agged ish we e eco ded.
Fou days pos -in ec ion, a seconda y in ec ion was conduc ed
wi h C. oge c esseyi as desc ibed by Lho en e e al. [36]. Ten
in ec i e ish pe ank we e used o e alua e he e ec i e bu den o
he pa asi e. We con i med he lack o sea lice (i.e., chalimus I) in
he SI ea men and an inc emen al esponse o se lemen in
bo h coin ec ion ea men s (LC = 2964.8 lice pe ish;
HC = 6064.8 lice pe ish).
S a is ical Analysis
Kaplan-Meie su i al cu es we e ob ained using he so wa e
Su i al ki 6 [49] o de ine he esponses o A lan ic salmon o
he di e en ea men s. A chi-squa ed es was used o e alua e
di e ences be ween ea men s [49]. To es ima e ixed e ec s and
hei in e ac ions, an ANOVA analysis was conduc ed using a
gene al lineal model (GLM) [50]. Mo ali y was de ined a 30 days
a e in ec ion wi h P. salmonis and ea ed as a no mally dis ibu ed
ai [43]. The GLM was:
yijklm~mzCizSjzFkzTCðÞ
lizCFikzSFjkzCSFijkzeijklm
whe e y
ijklm
is he ish mo ali y condi ion, mis he popula ion
mean, C
i
is he ea men e ec (SI, LC o HC), S
j
is he sex
( emale o male), F
k
is he ull sib amily e ec (1,2,3,…, 15),
T(C)
li
is he l
h
ank wi hin he i
h
ea men e ec (C), CF
ik
is he
ea men by amily in e ac ion, SF
jk
is he sex by amily
in e ac ion, CSF
ijk
is he ea men by sex by amily in e ac ion
and e
ijklm
is he andom esidual e ec . The CF
ik
in e ac ion
de e mines whe he amilies esis an o SI a e also esis an o LC
o HC coin ec ion.
A quan i a i e gene ic analysis o he esis ance o P. salmonis was
conduc ed o each in ec ion ea men o compa e es ima es o
he addi i e gene ic a iance o he mo ali y ai e alua ed. A
h eshold model (TM) was assumed o es ima e a iance
componen s [51]. This model assumes a no mal unde lying
liabili y a iable lde e mining he ca ego ical ou comes o he es -
pe iod su i al, such ha l
ijk
#0 co esponds o Y
ijk =
0 and l
ijk
.0
co esponds o y
ijk =
1. The esidual a iance o lwas assumed o
be 1.
P (yijk~1) ~P (lijkw0) ~W(w0ih)
Figu e 1. Mo ali y cu es o A lan ic salmon coin ec ed wi h
P. salmonis
and
C. oge c esseyi
.The da a show he cumula i e mo ali y o
h ee eplica es ( anks) (R1–R3) o h ee di e en scena ios: single in ec ion (SI) wi h P. salmonis and co-in ec ion wi h wo le els o in es a ion
p essu e o C. oge c esseyi (low p essu e o coin es a ion (LC) = 44 copepodi es pe ish; high p essu e o coin es a ion (HC) = 88 copepodi es pe ish).
Each eplica e had app oxima ely 182 pedig eed ish ha we e ee o disease. The a ow indica es he day o coin ec ion.
doi:10.1371/jou nal.pone.0095397.g001
Resis ance o Coin ec ion in A lan ic Salmon
PLOS ONE | www.plosone.o g 3 Ap il 2014 | Volume 9 | Issue 4 | e95397
whe e W(*) co esponds o he s anda d no mal dis ibu ion, w’
i
is
he incidence ec o ha links he da a wi h he pa ame e s ha
de ine he mean o he dis ibu ion o he liabili y indexed by he
pa ame e s in hand hcon ains he popula ion mean, he addi i e
gene ic alue and he signi ican (P,0.05) en i onmen al e ec s
(sex, challenge ank, and ini ial weigh as co a ia e).
Because he same amilies we e ep esen ed in he h ee
in ec ion ea men s (SI, LC and HC), he gene ic co ela ion o
P. salmonis esis ance in di e en in ec i e scena ios measu es he
in e ac ion ha de e mines whe he amilies esis an o SI a e also
esis an o LC o HC coin ec ion. A se o h ee bi a ia e linea
model (LM) analyses was used o es ima e he gene ic co ela ion
o esis ance among he di e en ea men s:
y~Xb zZa ze
whe e yis he obse a ions ec o o he p oposed ai s (SI, LC
o HC), Xis he design ma ix, bis he ec o o signi ican
Figu e 2. Kaplan–Meie su i al unc ion o A lan ic salmon coin ec ed wi h
P. salmonis
and
C. oge c esseyi
.The su i al unc ion
ep esen s he esis ance o he A lan ic salmon (i.e., he p opo ion ha had no died on each day ollowing challenge) in h ee di e en ea men s:
single in ec ion (SI) wi h P. salmonis and coin ec ion wi h wo le els o in es a ion p essu e o he sea louse C. oge c esseyi (low p essu e o
coin ec ion (LC) = 44 copepodi es pe ish; high p essu e o co in es a ion (HC) = 88 copepodi es pe ish).
doi:10.1371/jou nal.pone.0095397.g002
Table 1. ANOVA esul s o mo ali y 30 days a e P. salmonis in ec ion.
Sou ce o a ia ion d SS SS% MS F P- alue
In ec ion ea men (I) 2 87.90 28.0% 43.940 310.29 0.0001
Sex (S) 1 1.75 0.6% 1.750 12.38 0.0004
Full-sib Family (F) 14 22.30 7.1% 1.590 11.25 0.0001
Tank wi hin I (T) 6 3.72 1.2% 0.620 4.38 0.0002
I6F 28 12.94 4.1% 0.460 3.26 0.0001
S6F 2 0.53 0.2% 0.260 1.87 0.1547
S6I6F 42 6.37 2.0% 0.150 1.07 0.3517
E o 1267 179.46 57.0%
To al 1362 314.98
doi:10.1371/jou nal.pone.0095397. 001
Resis ance o Coin ec ion in A lan ic Salmon
PLOS ONE | www.plosone.o g 4 Ap il 2014 | Volume 9 | Issue 4 | e95397
(P,0.05) ixed e ec s wi hin each es (sex, challenge ank and
ini ial weigh as a co a ia e), Zis he incidence ma ix o he
andom e ec s, ais he b eeding alues ec o and eis he esidual
e o ec o .
The co a iance s uc u e o andom e ec s was:
Va ~ai
aj

~As2aii As2aij
As2aij As2ajj
"#
;Va ei
ej

~Is2eii Is2eij
Is2eij Is2ejj
"#
whe e a
i/j
and e
i/j
a e he ec o s o addi i e gene ic and esidual
alues o ai s i/j, espec i ely; Ais he addi i e gene ic
ela ionship ma ix; Iis he iden i y ma ix; s
2
a
ii/jj
and s
2
e
ii/jj
a e he a iances o addi i e gene ic and esidual e ec s,
espec i ely, o ai s i/j and s
2
a
ij
and s
2
e
ij
a e he co a iances
o addi i e gene ic and esidual e ec s, espec i ely, o he i h and
j h ai s.
Res ic ed Maximum Likelihood (REML) [52] and As eml
so wa e [53] we e used o sol e he TM and LM models and
ob ain he gene ic pa ame e s.
Resul s
De elopmen o Pisci icke siosis wi h and wi hou
Coin ec ion wi h Sea Lice
The de elopmen o pisci icke siosis was con inuously eco ded
o e 53 days un il mo ali y eached 544/544 (100%) and 545/
545 (100%) in bo h coin ec ion ea men s (Figu e 1). A ha ime,
mo ali y in he g oup ha ecei ed he single in ec ion wi h P.
salmonis only eached 251/545 (46%). A he beginning o he
cohabi a ion challenge wi h P. salmonis, a small inc ease in
mo ali y was obse ed (day 4). This inc ease was likely a
consequence o he sea lice in ec ion p ocedu e and no a di ec
consequence o coin ec ion. A 14–16 days pos -in ec ion, mo al-
i y associa ed wi h pisci icke siosis was obse ed in cohabi an
ish, and his esul was con i med by PCR a he beginning o he
ou b eak in dead ish. The daily mo ali y a e was lowe in single
han in coin ec ion scena ios (Figu e 1), bu no di e ences we e
obse ed be ween he coin ec ion ea men s.
Consis en wi h he mo ali y pa e n p e iously desc ibed,
Kaplan-Meie su i al cu es (Figu e 2) con i med ha coin ec-
ion o P. salmonis and C. oge c esseyi signi ican ly (p,0.05) educed
he su i al o A lan ic salmon compa ed o single in ec ion wi h P.
salmonis. Howe e , high pa asi e bu den did no signi ican ly
educe he su i al o A lan ic salmon compa ed o low pa asi e
bu den (P.0.05).
Gene ic Resis ance o A lan ic Salmon o Single and
Coin ec ion
As shown in Table 1, all main ixed e ec s signi ican ly a ec ed
he mo ali y o A lan ic salmon challenged wi h P. salmonis and
coin ec ed wi h C. oge c esseyi. The in ec ion e ec (I) was highly
signi ican (P,0.001) and showed he highes ela i e alue o he
associa ed sum o squa es o e he o al a iabili y o mo ali y
(28%). The e ec o he ull-sib amily (F) and i s in e ac ion wi h
he ea men e ec (F6I) we e also highly signi ican (P,0.001).
These e ec s showed a ela i e in luence o 7% and 4%,
espec i ely, on he a iabili y o mo ali y. Sex and ank wi hin
in ec ion ea men e ec s also signi ican ly a ec ed mo ali y.
Howe e , hei con ibu ions o he o e all a iabili y o mo ali y
we e less han 2%.
Quan i a i e gene ic pa ame e s o he esis ance o A lan ic
salmon o P. salmonis o he h ee ea men s o single and
coin ec ion a e shown in Table 2. The he i abili y o esis ance was
e y simila be ween ea men s and o medium magni ude (0.17–
0.24). Resis ance o he single in ec ion wi h P. salmonis did no
co ela e pheno ypically o gene ically wi h esis ance o P. salmonis
upon coin ec ion wi h he sea louse C. oge c esseyi (Table 2).
Con e sely, a high and signi ican gene ic co ela ion o esis ance
o P. salmonis was obse ed be ween he wo coin ec ion ea men s
(
g
LC-HC = 0.9960.01), p o iding solid e idence ha hese
esis ance alues a e measu emen s o he same ai .
Discussion
We ha e demons a ed o he i s ime ha he sea louse C.
oge c esseyi, as a seconda y pa hogen, signi ican ly educes he
esis ance o A lan ic salmon o he bac e ium P. salmonis. The
p e alence o C. oge c esseyi in Chilean salmon a ms app oaches
100% in some seasons (i.e., sp ing and summe ) and geog aphic
egions [27], [54]. The e o e, i s e ec on A lan ic salmon
mo ali y may be highe han p e iously hough . In A lan ic
salmon, coin ec ions o sea lice and o he pa hogens such as he
amoeba Neopa amoeba pe u ans ha e also been epo ed in he USA
[23] and in Chilean salmon a ms [24]. Bo h o hese s udies
sugges ed ha sea lice may play an impo an ole in he
epidemiology o amoebic gill disease caused by Neopa amoeba
pe u ans and/o in mo ali y o A lan ic salmon in sea a ms.
Simila ly, Valdes-Donoso e al. [25] epo ed ha mos o he
ISAV ou b eaks be ween 2007 and 2009 in he X
h
egion o Chile
we e associa ed wi h high sea lice bu dens. The educed su i al
upon coin ec ion in A lan ic salmon migh be explained by he
di ec skin damage caused by pa asi es ha allows o he pa hogens
o en e he ish [55]. Al e na i ely, i may esul om he sys emic
e ec s o immunosupp ession caused by sea lice [56].
Gene ic a ia ion in esis ance o disease in salmonids has been
epo ed o single in ec ions o pa hogens in A lan ic salmon [40],
[57], [58], [36], [42], [35], ainbow ou [59], [60], [61], [62],
[63], [64], Coho salmon [41] and b ook cha [42]. Howe e ,
gene ic a ia ion in he esis ance o coin ec ion by wo pa hogens
has no been p e iously es ima ed in salmonids. Using da a om a
a med popula ion o A lan ic salmon, we demons a ed gene ic
a ia ion o esis ance o P. salmonis upon coin ec ion wi h he sea
louse C. oge c esseyi. Sea lice in ec ions ha e been epo ed in
salmon a ms a ound he wo ld [10], bu coin ec ion wi h bac e ia,
i uses o pa asi es has been minimally in es iga ed. Resis ance o
coin ec ion has wo impo an implica ions o salmon b eeding.
Fi s , i coin ec ion is common, selec ion o disease esis ance o
Table 2. Es ima es o he i abili y (on diagonal), pheno ypic
(abo e diagonal) and gene ic (below diagonal) co ela ions (6
SE) in esis ance o A lan ic salmon be ween single in ec ion
(SI) wi h P. salmonis, and co-in ec ion wi h wo inc emen al
le els he o sea louse C. oge c esseyi (low p essu e o
coin es a ion (LC) = 44 copepodi es pe ish; high p essu e o
coin es a ion (HC) = 88 copepodi es pe ish).
SI LC HC
SI 0.2360.07* 20.0460.09
ns
0.0660.07
ns
LC 20.1460.33
ns
0.1760.08* 0.2160.01*
HC 0.3260.34
ns
0.9960.01* 0.2460.07*
ns: No signi ican ly di e en om ze o, p.0.05; *; signi ican ly di e en om
ze o, p,0.05.
doi:10.1371/jou nal.pone.0095397. 002
Resis ance o Coin ec ion in A lan ic Salmon
PLOS ONE | www.plosone.o g 5 Ap il 2014 | Volume 9 | Issue 4 | e95397

wo o mo e pa hogens, e alua ed independen ly as p oposed by
Ødega˚ d e al. [65], could be an ine icien me hod unless
esis ance o single and coin ec ion is posi i ely co ela ed. Second,
e alua ion o esis ance o wo di e en pa hogens could be
pe o med in a simple assay, educing cos s associa ed wi h
labo a o y es ing. Fu he s udies a e necessa y o de e mine
whe he esis ance o coin ec ion by P. salmonis and C. oge c esseyi
o o coin ec ion by o he pa hogens ele an o salmon a ming
such as ISAV, Ae omonas salmonicida o Neopa amoeba pe u ans occu s
in o he popula ions o salmonids.
The gene ic co ela ion o esis ance among a ious A lan ic
salmon pa hogens has been desc ibed o some bac e ia [66], [67],
[68], [69], [70], [71] and i uses [69], [71], [72]. Howe e , he
gene ic co ela ion o esis ance be ween single and coin ec ion o
wo pa hogens has no been p e iously es ima ed in salmonids.
Ou esul s s ongly sugges ha he esis ance o A lan ic salmon
o a single in ec ion o P. salmonis and ha o coin ec ion wi h he
sea louse C. oge c esseyi a e no gene ically ela ed. The e o e, we
can in e ha he bes s a egy o de eloping esis ance o P.
salmonis should conside coin ec ion wi h sea lice. Howe e , u he
s udies a e necessa y o es ablish whe he he esis ance o
coin ec ion obse ed in expe imen al condi ions co ela es wi h
highe su i al a es in he ield. A high gene ic co ela ion o
esis ance be ween esh and sea wa e has been desc ibed o
o he diseases such as u unculosis, sea lice and IPN [67], [38],
[73].
Conclusion
In ec ion wi h he sea louse C. oge c esseyi, as a seconda y
pa hogen, educes he esis ance o A lan ic salmon o he
pa hogen P. salmonis. Resis ance o coin ec ion o Pisci icke sia
salmonis and Caligus oge c esseyi in A lan ic salmon is a he i able
ai . The absence o a gene ic co ela ion be ween he esis ance
o single in ec ion and ha o coin ec ion indica es ha di e en
genes con ol hese p ocesses. Fu he s udies a e necessa y o
in es iga e he e ec s o coin ec ion when he sea louse is he
p ima y pa hogen. I is clea ha coin ec ion o di e en
pa hogens and esis ance o coin ec ion needs o be conside ed
in u u e esea ch on salmon a ming, selec i e b eeding and
conse a ion.
Acknowledgmen s
The au ho s would like o hank Ma ı
´n He ia o his aluable con ibu ion
o he de elopmen o he expe imen s in Aquad ice S.A.
Au ho Con ibu ions
Concei ed and designed he expe imen s: JPL JAG RN. Pe o med he
expe imen s: JPL JAG. Analyzed he da a: JPL JAG. Con ibu ed
eagen s/ma e ials/analysis ools: BV MJC. W o e he pape : JPL JAG.
Con ibu ed o designing he expe imen s and analyzing he da a: BV
MJC.
Re e ences
1. Mulcahy D, F ye JL (1976). Double in ec ion o ainbow ou y wi h IHN and
IPN i uses. Am Fish Soc/Fish Heal h Sec Newsl 5: 5–6.
2. Vilas MP, Rod ı
´guez S, Pe ez S (1994) A case o coin ec ion o IPN and IHN
i us in a med ainbow ou in Spain. Bull Eu Assoc Fish Pa hol 14 : 1–4.
3. Densmo e CL, O inge CA, Blaze VS, Iwanowicz LR (2004) Immunomod-
ula ion and disease esis ance in pos yea ling ainbow ou in ec ed wi h
Myxobolus ce eb alis, he causa i e agen o whi ling disease. J Aqua Anim Heal h
16: 73–82.
4. Johansen LH, Somme AI (2001). In ec ious panc ea ic nec osis i us in ec ion
in A lan ic salmon Salmo sala pos -smol a ec s he ou come o seconda y
in ec ions wi h in ec ious salmon anaemia i us o Vib io salmonicida. Dis
Aqua O gan 47: 109–117.
5. Johansen LH, Eggse G, Somme AI (2009) Expe imen al IPN i us in ec ion o
A lan ic salmon pa ; ecu ence o IPN and e ec s on seconda y bac e ial
in ec ions in pos -smol s. Aquacul u e 290: 9–14.
6. Alonso M, Rod ı
´guez Sain -Jean S, Pe´ ez-P ie o SI (2003) Vi ulence o
In ec ious hema opoie ic nec osis i us and In ec ious panc ea ic nec osis i us
coin ec ion in ainbow ou (Onco hynchus mykiss) and nucleo ide sequence
analysis o he IHNV glycop o ein gene. A ch Vi ol 148: 1507–1521.
7. Ta alla C, Rod ı
´guez Sain -Jean S, Pe´ ez-P ie o S (2006) Immunological
consequences o he coin ec ion o b own ou (Salmo u a) wi h in ec ious
hema opoie ic nec osis i us (IHNV) and in ec ious panc ea ic nec osis i us
(IPNV). Aquacul u e 256: 15–22.
8. By ne N, Cas ic J, Lamou F, Cabon J, Quen el C (2008) S udy o he i al
in e e ence be ween in ec ious panc ea ic nec osis i us (IPNV) and in ec ious
haema opoie ic nec osis i us (IHNV) in ainbow ou (Onco hynchus mykiss). Fish
Shell ish Immun, 24: 489–497.
9. Rod ı
´guez Sain -Jean S, Pe´ ez-P ie o S (2007) E ec s o salmonid ish i uses on
Mx gene exp ession and esis ance o single o dual i al in ec ions. Fish Shell ish
Immun 23 (2): 390–400.
10. Cos ello MJ (2009) The global economic cos o sea lice o he salmonid a ming
indus y. J Fish Dis 32: 115–118.
11. Cos ello MJ (2009) How sea lice om salmon a ms may cause wild salmonid
declines in Eu ope and No h Ame ica and be a h ea o ishes elsewhe e. P oc
Roy Soc B 276: 3385–3394.
12. K kosˇek M, Fo d JS, Mo on A, Lele S, Mye s RA, e al. (2007) Declining wild
salmon popula ions in ela ion o pa asi es om a m salmon. Science 318:
1772–1775.
13. Skaala Ø, Ka˚la˚s S, Bo gs øm R (2014) E idence o salmon lice-induced
mo ali y o anad omous b own ou (Salmo u a) in he Ha dange jo d,
No way, Ma ine Biology Resea ch, 10: 3, 279–288.
14. Cos ello MJ (2006) Ecology o sea lice pa asi ic on a med and wild ish. T ends
Pa asi ol 22: 475–483.
15. Conno s BM, Ha g ea es NB, Jones SRM, Dill LM (2010) P eda ion in ensi ies
pa asi e exposu e in a salmonid ood chain. J Appl Ecol 47: 1365–1371.
16. K kosˇek M, Conno s B, Mages P, Peacock S, Fo d H, e al. (2011) Fish a ms,
pa asi es, and p eda o s: Implica ions o salmon popula ion dynamics. Ecol
Appl 21: 897–914.
17. Fins ad B, Bjø n PA, G imnes A, H ids en NA (2000) Labo a o y and ield
in es iga ions o salmon lice [Lepeoph hei us salmonis (K oye )] in ec a ion on
A lan ic salmon (Salmo sala L) pos -smol s. Aquac Res 31: 795–803.
18. Fas MD, Muise DM, Easy RE, Ross NW, Johnson S (2006) The e ec s o
Lepeoph hei us salmonis in ec ions on he s ess esponse and immunological s a us
o A lan ic salmon (Salmo sala ). Fish Shell ish Immun 21: 228–241.
19. MacKinnon BM (1998). Hos ac o s impo an in sea lice in ec ions. ICES J
Ma Sci 55: 188–192.
20. Tully O, Nolan DT (2002) A e iew o he popula ion biology and hos -pa asi e
in e ac ions o he sea louse Lepeoph hei us salmonis (Copepoda: Caligidae).
Pa asi ology 124: S165–S182.
21. Pike AW, Wadswo h SL (1999) Sea lice on salmonids: hei biology and con ol.
Ad Pa asi ol 44: 223–337.
22. Mus a a A, Spea e DJ, Daley J, Conboy GA, Bu ka JF (2000) Enhanced
suscep ibili y o seawa e cul u ed ainbow ou , Onco hynchus mykiss (Walbaum),
o he mic ospo idian Loma salmonae du ing a p ima y in ec ion wi h he sea
louse, Lepeoph hei us salmonis. J Fish Dis 23: 337–341.
23. Nowak BF, B yan JB, Jones S (2010) Do salmon lice, Lepeoph hei us salmonis, ha e
a ole in he epidemiology o amoebic gill disease caused by Neopa amoeba
pe u ans?. J Fish Dis 33: 683–687.
24. Bus os PA, Young ND, Rozas MA, Bohle HM, Ilde onso RS, Mo ison RN,
Nowak BF (2011) Amoebic gill disease (AGD) in A lan ic salmon (Salmo sala )
a med in Chile. Aquacul u e 310 (3–4): 281–288.
25. Valdes-Donoso P, Ma dones FO, Ja pa M, Ulloa M, Ca pen e TE, Pe ez AM
(2013) Co-in ec ion pa e ns o in ec ious salmon anaemia and sea lice in a med
A lan ic salmon, Salmo sala L., in sou he n Chile (2007–2009). J Fish Dis 36:
353–360.
26. Zagmu -Ve ga a FJ, Ca pen e TE, Ha e TB, Hed ick RP (2005) Spa ial and
empo al a ia ions in sea lice (Copepoda: Caligidae) in es a ions o h ee
salmonid species a med in ne pens in Sou he n Chile. Dis Aqua O gan 64:
163–173.
27. Rozas M, Asencio G (2007) E aluacio´n de la Si uacion Epidemiolo´gica de la
Caligiasis en Chile: Hacia una es a egia de con ol e ec i a. Salmociencia 2 (1):
43–59.
28. Leal J, Woywood D (2007). Pisci icke siosis en Chile: A ances y pe spec i as
pa a su con ol. Salmociencia 2: 34–42.
29. Boxshall G, B a o S (2000) On he iden i y o common Caligus (Copepoda:
Siphonos oma oida: Caligidae) om salmonid ne pen sys ems in sou he n Chile.
Con ib Zoo 69: 137–146.
30. F ye JL, Lannan CN, Ga ce´s LH, La enas JJ, Smi h PA (1990) Isola ion o a
icke siales-like o ganism om diseased Coho salmon in Chile. Fish Pa hol 25:
107–114.
Resis ance o Coin ec ion in A lan ic Salmon
PLOS ONE | www.plosone.o g 6 Ap il 2014 | Volume 9 | Issue 4 | e95397
31. C i anich JD, Ga a e NO, Smi h CE (1991) The isola ion o a icke sia-like
o ganism causing disease and mo ali y in Chilean salmonids and i s
con i ma ion by Koch’s pos ula e. J Fish Dis 14: 121–145.
32. F ye JL, Lannan CN, Gio annoni SJ, Wood ND (1992) Pisci icke sia salmonis
gen. no ., sp. no ., he causa i e agen o an epizoo ic disease in salmonid ishes.
In J Sys Bac 42: 120–126.
33. Gagge o A, Cas o H, Sandino AM (1995) Fi s isola ion o Pisci icke sia salmonis
om coho salmon, Onco hynchus kisu ch (Walbaum), and ainbow ou ,
Onco hynchus mykiss (Walbaum), du ing he eshwa e s age o hei li e cycle. J
Fish Dis 18: 277–279.
34. F ye JL, Hed ick RP (2003) Pisci icke sia salmonis: a G am-nega i e in acellula
bac e ial pa hogen o ish. J Fish Dis 26: 251–262.
35. Ya´n˜ez JM, Bange a R, Lho en e JP, Oya zu´n M, Nei a R (2013) Quan i a i e
gene ic a ia ion o esis ance agains Pisci icke sia salmonis in A lan ic salmon
(Salmo sala ). Aquacul u e 414: 155–159.
36. Lho en e JP, Galla do JA, Villanue a B, A aya A, To ealba DA, Toledo XE,
Nei a R (2012) Quan i a i e gene ic basis o esis ance o Caligus oge c esseyi sea
lice in a b eeding popula ion o A lan ic salmon (Salmo sala ). Aquacul u e 324–
325: 55–59.
37. Glo e KA, Aasmunds ad T, Nilsen F, S o se A, Skaala O (2005) Va ia ion o
A lan ic salmon amilies (Salmo sala L.) in suscep ibili y o he sea lice
Lepeoph hei us salmonisand Caligus elonga us. Aquacul u e 245: 19–30.
38. Kols ad K, Heuch PA, Gje de B, Gjed em T, Sal e R (2005) Gene ic a ia ion
in esis ance o A lan ic salmon (Salmo sala ) o he salmon louse Lepeoph hei us
salmonis. Aquacul u e 247: 145–151.
39. Gha bi K, Glo e KA, S one LC, MacDonald ES, Ma hews L, G imhol U,
S ea MJ (2009) Gene ic dissec ion o MHC-associa ed suscep ibili y o
Lepeoph hei us salmonis in A lan ic salmon. BMC Gene 10: 20.
40. Mus a a A, MacKinnon BM (1999) Gene ic a ia ion in suscep ibili y o A lan ic
salmon o he sea louse Caligus elonga us No dmann, 1832. Can J Zool 77: 1332–
1335.
41. Wi hle R, E elyn T (1990) Gene ic a ia ion in esis ance o bac e ial kidney
disease wi hin and be ween wo s ains o coho salmon om B i ish Columbia.
T ans Am Fish Soc 119: 1003–1009.
42. Pe y GML, Ta e P, C oise ie e S, Belhumeu P, Be na chez L (2004) Gene ic
a iance and co a iance o 0+b ook cha (Sal elinus on inalis) weigh and
su i al ime o u unculosis (Ae omonas salmonicida) exposu e. Aquacul u e 235:
263–271.
43. Ødega˚ d J, Olesen I, Gje de B, Kleme sdal G (2006) E alua ion o s a is ical
models o gene ic analysis o challenge es da a on u unculosis esis ance in
A lan ic salmon (Salmo sala ): p edic ion o ield su i al. Aquacul u e 259: 116–
123.
44. Hol en-Ande sen L, Dalsgaa d I, Buchmann K (2012) Bal ic salmon, Salmo sala ,
om Swedish i e Lule A
¨l is mo e esis an o u unculosis compa ed o
ainbow ou . Plos One: 7e29571.
45. Go´mez D, Coneje os P, Consueg a S, Ma shall SH (2011) MHC media ed
esis ance o Pisci icke sia salmonis in salmonids a med in Chile. Aquacul u e 318:
15–19.
46. Jones SRM (2011) Mechanisms o Resis ance among Salmon o he Pa asi ic
Copepod Lepeoph hei us salmonis. J Aquac Res De elopmen S2: 003.
47. A aya A, Mancilla M, Lho en e JP, Nei a R, Galla do JA (2012) Expe imen al
challenges o A lan ic salmon Salmo sala wi h inc emen al le els o copepodids o
sea louse Caligus oge c esseyi: e ec s on in es a ion and ea ly de elopmen . Aquac
Res 43: 1904–1908.
48. Gonza´lez L, Ca ajal J, Geo ge-Nascimen o M (2000) Di e en ial in ec i i y o
Caligus lexispina (Copepoda:Caligidae) in h ee a med salmonids in Chile.
Aquacul u e 183, 13–23.
49. Duc ocq V, So¨lkne J, Me´sza´ os G (2010) Su i al Ki 6 - A so wa e package
o su i al analysis. In: 9 h Wo ld Cong ess on Gene ics o Li es ock
P oduc ion, Augus 1–6, 2010, Leipzig, Ge many.
50. SAS INSTITUTE INC, 1993. Use ’s guide: S a is ics, Ve sio´n 6.03. Edi ion.
SAS Ins i u e Inc., Ca y, NC. 956 p.
51. Falcone DS, Mackay TFC. (1996) In oduc ion o quan i a i e gene ics.
London and New Yo k, Longman G oup Limi ed. Fou h Edi ion. 464 p.
52. Johnson DL, Thompson R (1995) Res ic ed maximum likelihood es ima ion o
a iance componen s o uni a ia e animal models using spa se ma ix
echniques and a Quasi-New on p ocedu e. J Dai y Sci 78: 449–456.
53. Gilmou AR, Cullis BR, Welham SJ, Thompson R (1999). ASREML Re e ence
Manual. 213 p.
54. Se napesca (2012) In o me Sani a io Salmonicul u a en Cen os Ma inos - An˜o
2012. Minis e io de Economı
´a, Fomen o y Recons uccio´n, Valpa aı
´so, Chile.
A ailable a : h p://www.se napesca.cl (accessed No embe 15, 2013).
55. Smi h PA, Piza o P, Ojeda P, Con e as J, Oyanedel S, La enas J (1999) Rou es
o en y o Pisci icke sia salmonis in ainbow ou Onco hynchus mykiss. Dis Aqua
O g 37: 165–172.
56. Tadiso TM, K asno A, Skugo S, A anasye S, Ho d ik I, Nilsen F (2011)
Gene exp ession analyses o immune esponses in A lan ic salmon du ing ea ly
s ages o in ec ion by salmon louse (Lepeoph hei us salmonis) e ealed bi-phasic
esponses coinciding wi h he copepod-chalimus ansi ion. BMC Genomics 12:
141.
57. Taylo RS, Wynne JW, Kube PD, Ellio NG (2007) Gene ic a ia ion o
esis ance o amoebic gill disease in A lan ic salmon assessed in a challenge
sys em. Aquacul u e 272 S1: S94–S299.
58. No is A, Foyle L, Ra cli J (2008) He i abili y o mo ali y in esponse o a
na u al pa´nc eas disease (SPDV) challenge in A lan ic salmon, Salmo sala L.,
pos -smol s on a Wes o I eland sea si e. J Fish Dis 31: 913–920.
59. Do son M, Quille E, Hollebecq MG, To hy C, Che assus B (1995) Selec ion o
ainbow ou esis ance o i al haemo hagic sep icaemia i us and
ansmission o esis ance by gynogenesis. Ve Res 26: 361–368.
60. Hen yon M, Jokumsen A, Be g P, Lund I, Pede sen PB, Olesen NJ,
Slie end ech WJ (2002) Gene ic a ia ion o g ow h a e, eed con e sion
e iciency, and disease esis ance exis s wi hin a a med popula ion o ainbow
ou . Aquacul u e 209: 59–76. E a um: Aquacul u e 216: 387–388.
61. Hen yon M, Pee Be g T, Olesen N, Kjae T, Slie end ech W, Jokumsen A,
Lund I (2005) Selec i e b eeding p o ides an app oach o inc ease esis ance o
ainbow ou (Oncho hynchus mykiss) o he diseases, en e ic edmou h disease,
ainbow ou y synd ome, and i al haemo hagic sep icaemia. Aquacul u e
250: 621–636.
62. Webe GM, Vallejo RL, Lank o d SE, Sil e s ein JT, Welch TJ (2008) Co isol
Response o a C owding S ess: He i abili y and Associa ion wi h Disease
Resis ance o Ye sinia ucke i in Rainbow T ou . N Am J Aquacul 70: 425–433.
63. Sil e s ein JT, Vallejo RL, Pal i Y, Leeds TD, Rex oad III CE, Welch TJ, Wiens
GD, Duc ocq V (2009) Rainbow ou esis ance o bac e ial cold-wa e disease
is mode a ely he i able and no ad e sely co ela ed wi h g ow h. J Anim Sci 87:
860–867.
64. Leeds TD, Sil e s ein JT, Webe GM, Vallejo RL, Pal i Y, Rex oad III CE,
E enhuis J, Hadidi S, Welch TJ, Wiens GD (2010) Response o selec ion o
bac e ial cold wa e disease esis ance in ainbow ou . J Anim Sci 88: 1936–
1946.
65. Ødega˚ d J, Ba anski M, Gje de B, Gjed em T (2011) Me hodology o gene ic
e alua ion o disease esis ance in aquacul u e species: challenges and u u e
p ospec s. Aquac Res 42: 103–114.
66. Gjed em T, Gjoen HM (1995) Gene ic a ia ion in suscep ibili y o A lan ic
salmon, Salmo sala L., o u unculosis, BKD and cold wa e ib iosis. Aquac Res
26: 129–134.
67. Gjøen HM, Re s ie T, Ulla O, Gje de B (1997). Gene ic co ela ions be ween
su i al o A lan ic salmon in challenge and ield es s. Aquacul u e 158: 277–
288.
68. Ødega˚ d J, Olesen I, Gje de B, Kleme sdal G (2007). Posi i e gene ic co ela ion
be ween esis ance o bac e ial ( u unculosis) and i al (in ec ious salmon
anemia) diseases in a med A lan ic salmon (Salmo sala ). Aquacul u e 271: 173–
177.
69. Kjoglum S, Hen yon M, Assmunds ad T, Ko sgaa d I (2008) Selec i e b eeding
can inc ease esis ance o A lan ic salmon o u unculosis, in ec ious salmon
anemia and in ec ious panc ea ic nec osis. Aquac Res 39: 498–505.
70. Gje de B, E ensen O, Ben sen HB, S o se A (2009) Gene ic (co) a ia ion o
accine inju ies and inna e esis ance o u unculosis (Ae omona salmonicida)and
In ec ious Salmon Anemia (ISA) in A lan ic salmon (Salmo sala L). Aquacul u e
287: 52–58.
71. D angshol TMK, Gje de B, Ødega˚ d J, Finne-F idell F, E ensen O, Ben sen
HB (2012) Gene ic co ela ions be ween disease esis ance, accine-induced side
e ec s and ha es body weigh in A lan ic salmon (Salmo sala ). Aquacul u e
324–325: 55–59.
72. Guy DR, Bishop SC, Woolliams JA, B o he s one S (2009) Gene ic pa ame e s
o esis ance o In ec ious Panc ea ic Nec osis in pedig eed A lan ic salmon
(Salmo sala ) pos -smol s using a educed animal model. Aquacul u e 290 (3–4):
229–235.
73. S o se A, S and C, We en M, Kjøglum S, Rams ad A (2007) Response o
selec ion o esis ance agains in ec ious panc ea ic nec osis in A lan ic salmon
(Salmo sala , L.). Aquacul u e 272 S1: S62–S68.
Resis ance o Coin ec ion in A lan ic Salmon
PLOS ONE | www.plosone.o g 7 Ap il 2014 | Volume 9 | Issue 4 | e95397