Análisis genómico de líneas divergentes seleccionadas para lacapacidad uterina

Abstract

[EN] Litter size is an economically important trait in rabbits. Maternal lines are usually selected for litter size and they are used in a three-way crossover to produce rabbit meat. Low response obtained after selection for litter size in closed populations led to the search for alternative methods of selection for improving more efficiently litter size. Selection for main components of litter size (ovulation rate and prenatal survival) has been proposed as a way to improve litter size. An experiment of divergent selection for uterine capacity was carried out in the Animal Breeding Unit of Polytechnic University of Valencia. Uterine capacity was defined as the maximum number of foetuses that a female is able to support up to birth when ovulation rate is not a limiting factor. Two divergent lines, one to increase uterine capacity (High Line) and one to decrease (Low Line) were selected during ten generations. Uterine capacity was assessed as litter size in unilaterally ovariectomized (ULO) does. After 10 generations, selection was relaxed for six generations. At the beginning of divergent selection process, embryos were vitrified from base population (Line V). In the generation 10, embryos were thawed and a contemporary reference population was established. In the 11th and 12th generations, blood samples were frozen from 90, 70 and 30 intact females from High, Low and reference line, respectively. Nowadays, the first SNPchip for genotyping in rabbits, 200K Affymetrix Axiom OrcunSNP Array, is available. Thus, main objective was to detect genomic areas associated with litter size in rabbits by GWAS and selection footprints in a divergent selection experiment for uterine capacity (Article 2). In addition, another objective was to study different scenarios of genetic structure for uterine capacity in order to detect positive associations by simulation. The drift genetic effect was also studied (Article 1). Results using 160 animals of divergent lines had advantages over using the same number of animals from only one line. A genetic structure of 10,010 QTN would have a greater positive predictive value. Genetic drift represented up to 14.52% of the selection response, but it was responsible that up to 50% QTNs fix. GWAS analysis showed four genomic regions associated with litter size (LS). One, five and four associated regions were found for ovulation rate (OR), implanted embryos (IE) and number born alive (NBA), respectively. These genomics regions were considered as putative QTLs. Putative QTLs were not detected for embryo, fetal and prenatal survival (ES, ES and SP, respectively) and number born dead (NBD). The regions of chromosome 17 explained 20.62% of the genomic variance of LS, being themselves the most ix relevant genomic region. The ERO1A gene, reported on expression analyses in these rabbit divergent lines, was found within the QTL on chromosome 17. In addition, new genomic areas were found. Their biological functions are related to the activity of prostanoid receptors, cytoplasmic components and to a negative regulation of cell proliferation. Main genes were BMP4, PTGDR ANKH and CDKN3. On the other hand, Fst were not found between the divergent lines, but six clusters were found between the low line of uterine capacity and the line V. Thus, our findings provide a new starting point for further genomic studies, in order to unravel the genetic basis of litter size and its components in rabbits. These could also provide useful information for future research on other selection strategies or the application of genomic selection in rabbit commercial populations.

[ES] Litter size is an economically important trait in rabbits. Maternal lines are usually selected for litter size and they are used in a three-way crossover to produce rabbit meat. Low response obtained after selection for litter size in closed populations led to the search for alternative methods of selection for improving more efficiently litter size. Selection for main components of litter size (ovulation rate and prenatal survival) has been proposed as a way to improve litter size. An experiment of divergent selection for uterine capacity was carried out in the Animal Breeding Unit of Polytechnic University of Valencia. Uterine capacity was defined as the maximum number of foetuses that a female is able to support up to birth when ovulation rate is not a limiting factor. Two divergent lines, one to increase uterine capacity (High Line) and one to decrease (Low Line) were selected during ten generations. Uterine capacity was assessed as litter size in unilaterally ovariectomized (ULO) does. After 10 generations, selection was relaxed for six generations. At the beginning of divergent selection process, embryos were vitrified from base population (Line V). In the generation 10, embryos were thawed and a contemporary reference population was established. In the 11th and 12th generations, blood samples were frozen from 90, 70 and 30 intact females from High, Low and reference line, respectively. Nowadays, the first SNPchip for genotyping in rabbits, 200K Affymetrix Axiom OrcunSNP Array, is available. Thus, main objective was to detect genomic areas associated with litter size in rabbits by GWAS and selection footprints in a divergent selection experiment for uterine capacity (Article 2). In addition, another objective was to study different scenarios of genetic structure for uterine capacity in order to detect positive associations by simulation. The drift genetic effect was also studied (Article 1). Results using 160 animals of divergent lines had advantages over using the same number of animals from only one line. A genetic structure of 10,010 QTN would have a greater positive predictive value. Genetic drift represented up to 14.52% of the selection response, but it was responsible that up to 50% QTNs fix. GWAS analysis showed four genomic regions associated with litter size (LS). One, five and four associated regions were found for ovulation rate (OR), implanted embryos (IE) and number born alive (NBA), respectively. These genomics regions were considered as putative QTLs. Putative QTLs were not detected for embryo, fetal and prenatal survival (ES, ES and SP, respectively) and number born dead (NBD). The regions of chromosome 17 explained 20.62% of the genomic variance of LS, being themselves the most ix relevant genomic region. The ERO1A gene, reported on expression analyses in these rabbit divergent lines, was found within the QTL on chromosome 17. In addition, new genomic areas were found. Their biological functions are related to the activity of prostanoid receptors, cytoplasmic components and to a negative regulation of cell proliferation. Main genes were BMP4, PTGDR ANKH and CDKN3. On the other hand, Fst were not found between the divergent lines, but six clusters were found between the low line of uterine capacity and the line V. Thus, our findings provide a new starting point for further genomic studies, in order to unravel the genetic basis of litter size and its components in rabbits. These could also provide useful information for future research on other selection strategies or the application of genomic selection in rabbit commercial populations.