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Genetic'dissection'of'growth'and' Meat'quality'traits'in'pigs''

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Genetic'dissection'of'growth'and' Meat'quality'traits'in'pigs'' ! ! ! UNIVERSITAT*AUTÒNOMA*DE*BARCELONA* Departament*de*Ciència*Animal*i*dels*Aliments* Facultat*de*Veterinària* CENTRE*DE*RECERCA*EN*AGRIGENÒMICA* Grup*de*Recerca*de*Genòmica*Animal* * GENETIC'DISSECTION'OF'GROWTH'AND' MEAT'QUALITY'TRAITS'IN'PIGS'' ANNA'PUIG'OLIVERAS' * PhD*Thesis*in*Animal*Production* Bellaterra,*September*2015* * Supervisors* Dr.*Josep*Maria*Folch*Albareda*****************Dra.*Maria*Ballester*Devis* El# Dr.# Josep# Maria# Folch# Albareda,# professor# titular# del# Departament# de# Ciència# Animal#i#dels#Aliments#de#la#Universitat#Autònoma#de#Barcelona,# # i# # la#Dra.#Maria#Ballester#Devis,#investigadora#del#Departament#de#Genètica#i#Millora# Animal#de#l’Institut#de#Recerca#i#Tecnologia#Agroalimentàries#(IRTA).## # CERTIFIQUEN:# Que# Anna$ Puig$ Oliveras# ha# realitzat# sota# la# seva# direcció# el# treball# de# recerca# "Genetic#dissection#of#growth#and#meat#quality#traits#in#pigs"#per#obtenir#el#grau#de# Doctora#per#la#Universitat#Autònoma#de#Barcelona.# # Que#aquest#treball#s'ha#dut#a#terme#al#Departament#de#Ciència#Animal#i#dels#Aliments# de#la#Facultat#de#Veterinària#de#la#Universitat#Autònoma#de#Barcelona#i#a#la#unitat#de# Genètica#Animal#del#Centre#de#Recerca#en#Agrigenòmica.# # Bellaterra,#a#15#de#juliol#de#2015# # # # Dr.#Josep#Maria#Folch#Albareda##########Dra.#Maria#Ballester#Devis# # ! $ ! CONTENT& & SUMMARY&/&RESUMEN&&.....................................................................................&&&&7& LIST&OF&TABLES&&..................................................................................................&&&&9& LIST&OF&FIGURES&&................................................................................................&&13& LIST&OF&PUBLICATIONS&&......................................................................................&&17& RELATED&PUBLICATIONS&BY&THE&AUTHOR&&..........................................................&&18& ABBREVIATIONS&&................................................................................................&&19& 1.&GENERAL&INTRODUCTION&&..............................................................................&&23& 1.1.#Porcine#meat#production##...........................................................................##25# 1.2.#Relevant#traits#in#the#porcine#industry##......................................................##26# # 1.2.1.#Growth,#carcass#conformation#and#composition##.......................##28# # 1.2.2.#Pork#intramuscular#fat#content#and#fatty#acid#composition##.......##29# 1.3.#Fatty#acid#metabolism##...............................................................................##30# 1.4.#Genomic#tools#to#study#traits#of#interest#in#porcine#production##...............##34# # 1.4.1.#QTLs,#GWAS#and#candidate#genes##..............................................##38# # 1.4.2.#NGS#technologies##.......................................................................##40# # 1.4.3.#eQTL#mapping#approach##............................................................##43# # 1.4.4.#MultiOtrait#network#analyses#for#complex#traits##.........................##44# 1.5.#IBMAP#cross#animal#material##.....................................................................##47# # 1.5.1.#Identification#of#QTLs#in#the#IBMAP#cross##..................................##48# # # 1.5.1.1.#FABP4#and#FABP5#candidate#genes#in#SSC4##..................##49# 2.&OBJECTIVES&&...................................................................................................&&51& 3.&PAPERS&AND&STUDIES&&....................................................................................&&55& Paper# I.# Analysis# of' FABP4# and# FABP5# gene# expression# and# polymorphisms# affecting#pig#fatty#acid#composition##.............................................................##57# Paper# II.# Differences# in# muscle# transcriptome# among# pigs# phenotypically# extreme#for#fatty#acid#composition##.............................................................##89# Paper#III.#A#CoOAssociation#Network#Analysis#of#the#Genetic#Determination#of# Pig#Conformation,#Growth#and#Fatness##.......................................................#103# Paper# IV.# ExpressionObased# GWAS# identify# variants,# gene# interactions# and# potential# key# regulators# affecting# the# intramuscular# content# and# fatty# acid# composition#in#porcine#meat##.......................................................................#125# ! 4.&GENERAL&DISCUSSION&&...................................................................................&163& 4.1.#QTL,#GWAS#and#candidate#gene#approaches#in#the#IBMAP#cross##.............#166# 4.2.#Studying#the#swine#muscle#transcriptome#using#RNAOSeq##........................#171# 4.3.#Networks#to#decipher#conformation,#growth#and#fatness#related#traits#in#pig #..........................................................................................................................#177# 4.4.# Gene# expression# study# of# 45# candidate# genes# for# the# muscle# lipid# metabolism#to#explore#gene#interactions#and#identify#key#regulators##............#181# 4.5.#Integrative#view##.........................................................................................#184# 4.6.#Future#directions#and#challenges##...............................................................#186# 5.&CONCLUSIONS&&...............................................................................................&189& 6.&REFERENCES&&..................................................................................................&193& 7.&ANNEXES&&.......................................................................................................&217& 7.1.# Supplementary# material# of# paper# I:# "Analysis# of# FABP4' and# FABP5' gene# expression#and#polymorphisms#affecting#pig#fatty#acid#composition"##.............#219# 7.1.1.#Supplementary#Tables#Paper#I##...........................................................#219# 7.1.2.#Supplementary#Figures#Paper#I##..........................................................#221# 7.2.# Supplementary# material# of# paper# II:# "Differences# in# muscle# transcriptome# among#pigs#phenotypically#extreme#for#fatty#acid#composition"##.....................#227# 7.2.1.#Supplementary#Tables#Paper#II##..........................................................#227# 7.2.2.#Supplementary#Figures#Paper#II##.........................................................#236# 7.3.#Supplementary#material#of#paper#III:#"A#CoOAssociation#Network#Analysis#of# the#Genetic#Determination#of#Pig#Conformation,#Growth#and#Fatness"##..........#237# 7.3.1.#Supplementary#Tables#Paper#III##.........................................................#237# 7.3.2.#Supplementary#Figures#Paper#III##........................................................#242# 7.4.# Supplementary# material# of# paper# IV:# "ExpressionObased# GWAS# identify# variants,# gene# interactions# and# potential# key# regulators# affecting# the# intramuscular#content#and#fatty#acid#composition#in#porcine#meat"##...............#247# 7.4.1.#Supplementary#Tables#Paper#IV##.........................................................#247# 7.4.2.#Supplementary#Figures#Paper#IV#.........................................................#272# ACKNOWLEDGEMENTS&&......................................................................................&275! ! SUMMARY' Pork" is" the" most" consumed" meat" worldwide." The" breeding" programs" have" been" working"towards"a"sustainable"pig"production"improving"reproduction"traits,"growth" and" meat" quality" traits." The" genetic" basis" determining" these" complex" and" economically"important"production"traits"remains"elusive"not"being"fully"understood." In"the"present"thesis"we"pursue"to"clarify"the"molecular"mechanisms"that"determine" growth"and"meat"quality"traits." The" functional" role" of" FABP4" and& FABP5" genes" in" determining" the" fatty" acid" composition"in"muscle"and"backfat"tissues"was"evaluated."Animals"inheriting"the"C" allele" for" FABP4:g.2634_2635insC& polymorphism" showed" higher" intramuscular" content" of" C16:0" and" C16:1(nG7)" fatty" acids" and," decreased" content" of" C18:2(nG6)" fatty" acid" and" higher" FABP4& expression" in" backfat." Moreover," FABP4:g.2634_2635insC"was"located"inside"a"PPARG"binding"site"suggesting"a"role"of" this" nuclear" receptor" in" the" regulation" of" FABP4" gene" expression.& The" FABP5:g.3000T>G" SNP" was" the" most" significant" marker" for" intramuscular" percentages" of" C18:1(nG9)," C18:2(nG6)," and" MUFA." However," this" variant" was" not" associated" with" FABP5& gene" expression," being" FABP5& gene" expression" in" muscle" regulated"by"other"genomic"regions"located"on"SSC4,"SSC6,"SSC9"and"SSC13." Aiming" to" identify" genes" and" pathways" affecting" the" intramuscular" fatty" acid" composition," the" muscle" transcriptome" of" two" groups" of" pigs" with" extreme" phenotypes"for"these"traits"was"analyzed."A"total"of"131"genes"mostly"related"to"lipid" metabolism" pathways" were" identified" as" differentially" expressed" between" groups." The" functional" analysis" showed" that" animals" with" a" higher" content" of" PUFA" presented" low" fatty" acid" and" glucose" uptake" resulting" in" an" inhibition" of" the" lipogenesis.""" GeneGbyGgene"approaches"used"until"now"are"limited"when"analyzing"complex"traits" usually"implying"several"genes"with"small"effects;"moreover,"they"ignore"functional" interactions."For"this"reason,"we"decided"to"apply"a"gene"network"approach"based"on" SNPGbyGSNP" coGassociation" analysis"
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