EPIGENETIC MECHANISMS REGULATE GENE EXPRESSION INDEPENDENTLY OF THE UNDERLYING DNA SEQUENCE, RELYING INSTEAD ON THE CHEMICAL MODIFICATION OF DNA AND HISTONE PROTEINS. THE PRESENT PROJECT IS PROPOSED WITHIN THE MAIN RESEARCH LINE OF OUR RESEARCH GROUP, GENETICS OF DAIRY SHEEP, AND AS A STEP FORWARD TO ADVANCE IN THE KNOWLEDGE OF THE GENETIC ARCHITECTURE OF COMPLEX TRAITS OF INTEREST IN DAIRY SHEEP CONSIDERING THAT THE RECOGNITION OF THE CONTRIBUTION OF EPIGENETICS TO PHENOTYPIC VARIATION IS INCREASING IN RECENT YEARS. THE GLOBAL OBJECTIVE OF THE PROPOSED PROJECT IS TO ANALYZE THE ROLE OF EPIGENETIC MARKS AND GENOMIC VARIANTS IN THE CONTROL OF THE TRANSCRIPTIONAL PROFILE OF DIFFERENT TISSUES WITH A PRODUCTIVE POTENTIAL IN DAIRY SHEEP. FOR THAT, WE WILL USE YOUNG FEMALE PREPUBERAL LAMBS, PREVIOUSLY SUBJECTED TO A SEVERE FEED RESTRICTION NUTRITIONAL CHALLENGE (NC) AT 3-5 MONTHS OF AGE, AND WILL STUDY HOW THIS NUTRITIONAL RESTRICTION MAY INFLUENCE IMMUNE RESPONSE AGAINST AN INFLAMMATORY CHALLENGE IN THE MAMMARY GLAND AND, ALSO, IF IT MAY HAVE A PUTATIVE TRANSGENERATIONAL EFFECT, FOR EXAMPLE INFLUENCING FATNESS TRAITS IN THEIR OFFSPRING. TO ACHIEVE THE GLOBAL AIM, WE PROPOSE THREE SPECIFIC OBJECTIVES. IN THE FIRST, WE WILL ANALYSE THE EFFECT OF THE DIFFERENTIAL GROWTH OF THE MAMMARY GLAND AND OF THE GENOMIC VARIABILITY OVER THE TRANSCRIPTIONAL CONTROL OF THE MAMMARY GLAND AND BLOOD CELLS (INCLUDING CYTOSINE METHYLATION USING WHOLE GENOME BISULFITE SEQUENCING, LNCRNA AND GLOBAL TRANSCRIPTOMIC ANALYSIS USING RNA-SEQ) IN ANIMALS SUBJECTED TO AN INFLAMMATORY CHALLENGE VERSUS A CONTROL GROUP. IN THE SECOND OBJECTIVE THE POTENTIAL IMPACT OF A MATERNAL NUTRITIONAL CHALLENGE AND OF THE GENOMIC VARIABILITY ON THE TRANSCRIPTIONAL CONTROL (CYTOSINE METHYLATION, LNCRNA AND WHOLE TRANSCRIPTOMIC ANALYSIS USING RNA-SEQ) OF THE PERIRENAL ADIPOSE TISSUE IN SUCKLING LAMBS WILL BE ANALYZED. IN THE THIRD OBJECTIVE THE MUTATIONS OVERLAPPING WITH THE DIFFERENTIAL EPIGENETIC MARKS IDENTIFIED IN THE INFLAMMATORY CHALLENGE BETWEEN THE TWO STUDIED GROUPS OF EWES (CONTROL AND NC) WILL BE INCLUDED IN A GENOTYPING PLATFORM TO BE VALIDATED IN A COMMERCIAL POPULATION OF ASSAF EWES WITH AVAILABLE BREEDING VALUES FOR THE SOMATIC CELL SCORE PHENOTYPE. THE MUTATIONS SHOWING SIGNIFICANT ASSOCIATIONS WITH THIS INDICATOR TRAIT OF MASTITIS RESISTANCE WILL BE CONSIDERED TO BE EXPLOITED IN BREEDING PROGRAMMES THROUGH A GS APPROACH. GLOBALLY, THIS PROJECT WILL PROVIDE AN INITIAL MAP OF EPIGENETIC MARKS IN THE SHEEP GENOME THAT WOULD EXPLAIN HOW EPIGENETIC MECHANISMS INFLUENCE PHENOTYPES. IN ADDITION TO GENERATE BASIC KNOWLEDGE, THE PROJECT WILL BE AN INITIAL STEP TOWARDS THE GENERATION OF PRACTICAL INFORMATION TO BETTER UNDERSTAND THE GXE INTERACTION TO INCREASE THE PRODUCTIVITY, SUSTAINABILITY AND RESILENCE OF DAIRY SHEEP. THE INTEGRATION OF ALL THIS INFORMATION, GENERATED THROUGH THE MOST MODEN GENOMIC TECHNIQUES, WILL HELP TO INCREASE OUR UNDERSTANDING OF THE GENETIC CONTROL OF COMPLEX TRAITS IN LIVESTOCK SPECIES.
