, Cette première partie est destinée à résumer les données et résultats acquis avant le début du stage afin de décrire la situation dans deux domaines : la cartographie génétique et les études fonctionnelles. 1.1 Etat des lieux des données génétiques

, Cependant à l'issue de ces premières analyses les intervalles de localisation de ces QTL étaient très larges, entre 20 et 40 cM. La première approche qui a été envisagée pour réduire l'intervalle des QTL est une approche dite backcross ou croisement en retour avec une des deux lignées parentales (en l'occurrence Lw), Le programme PORQTL initié en 1991 a permis de mettre en évidence un grand nombre de régions, affectant notamment des caractères de croissance et d'engraissement. Les QTL présentant les effets les plus importants ont été localisés sur les chromosomes 1, 2, 4

. De-cette-façon, Cela nous a permis de réduire une première fois l'intervalle de localisation du QTL à 15 cM entre les marqueurs MCS455C8A et MCS840B11A (Figure 34). Cependant, du fait de la dominance partielle de l'allèle Large White et de résultats contradictoires, nous avons été amenés à continuer cette approche en testant les pères recombinants avec des femelles localement congéniques MsMs (cf partie, 2.2.3.3 Création d'individus BC localement congéniques). La production et le testage de 4 nouveaux pères recombinants ont alors permis de réduire à nouveau de façon significative l, verrats BC2 et 1 verrat BC3) ont été analysés par testage sur descendance avec des femelles LwLw (q/q) afin de déterminer leur statut au QTL

, Listes des références bibliographiques

I. A. Adzhubei, S. Schmidt, L. Peshkin, V. E. Ramensky, A. Gerasimova et al., A method and server for predicting damaging missense mutations, Nature Methods, vol.7, pp.248-249, 2010.
DOI : 10.1038/nmeth0410-248
URL : http://europepmc.org/articles/pmc2855889?pdf=render

D. B. Anderson and R. G. Kauffman, Cellular and enzymatic changes in porcine adipose tissue during growth, J. Lipid Res, vol.14, pp.160-168, 1973.

S. I. Anderson, N. L. Lopez-corrales, B. Gorick, A. , and A. L. , A large-fragment porcine genomic library resource in a BAC vector, Mamm. Genome, vol.11, pp.811-814, 2000.

L. Andersson, C. S. Haley, H. Ellegren, S. A. Knott, M. Johansson et al., Genetic mapping of quantitative trait loci for growth and fatness in pigs, Science, vol.263, pp.1771-1774, 1994.

A. L. Archibald, C. S. Haley, J. F. Brown, S. Couperwhite, H. A. Mcqueen et al., The PiGMaP consortium linkage map of the pig, 1995.

, Mamm. Genome, vol.6, pp.157-175

A. L. Archibald, L. Bolund, C. Churcher, M. Fredholm, M. A. Groenen et al., Pig genome sequence-analysis and publication strategy, BMC Genomics, vol.11, p.438, 2010.
DOI : 10.1186/1471-2164-11-438
URL : https://bmcgenomics.biomedcentral.com/track/pdf/10.1186/1471-2164-11-438

S. Asakawa, I. Abe, Y. Kudoh, N. Kishi, Y. Wang et al., Human BAC library: construction and rapid screening, Gene, vol.191, pp.69-79, 1997.
DOI : 10.1016/s0378-1119(97)00044-9

M. Banville, J. Riquet, D. Bahon, M. Sourdioux, C. et al., Genetic parameters for litter size, piglet growth and sow's early growth and body composition in the Chinese-European line Tai Zumu, Journal of Animal Breeding and Genetics, vol.132, pp.328-337, 2015.

F. Berg, S. Stern, K. Andersson, L. Andersson, and M. Moller, Refined localization of the FAT1 quantitative trait locus on pig chromosome 4 by marker-assisted backcrossing, BMC Genetics, vol.7, p.17, 2006.

J. P. Bidanel, D. Milan, N. Iannuccelli, Y. Amigues, M. Boscher et al., Détection de locusa effets quantitatifs dans le croisement entre les races porcines Large White et Meishan. Résultats et perspectives, vol.32, pp.369-383, 2000.

J. Bidanel, D. Milan, N. Iannuccelli, Y. Amigues, M. Boscher et al., Detection of quantitative trait loci for growth and fatness in pigs, Genetics Selection Evolution, vol.33, pp.289-310, 2001.
URL : https://hal.archives-ouvertes.fr/hal-00894376

D. Boichard, P. Le-roy, H. Leveziel, and J. Elsen, Utilisation des marqueurs moleculaires en genetique animale, INRA Prod. Anim, vol.11, pp.67-80, 1998.

D. Botstein, R. L. White, M. Skolnick, D. , and R. W. , Construction of a genetic linkage map in man using restriction fragment length polymorphisms, Am. J. Hum. Genet, vol.32, pp.314-331, 1980.

L. Cai, J. F. Taylor, R. A. Wing, D. S. Gallagher, S. S. Woo et al., Construction and characterization of a bovine bacterial artificial chromosome library, Genomics, vol.29, pp.413-425, 1995.

C. Charlier, W. Coppieters, F. Farnir, L. Grobet, P. L. Leroy et al., The mh gene causing double-muscling in cattle maps to bovine Chromosome 2, Mamm. Genome, vol.6, pp.788-792, 1995.

S. Cinti, The adipose organ, Prostaglandins Leukot. Essent. Fatty Acids, vol.73, pp.9-15, 2005.

A. Darvasi, Experimental strategies for the genetic dissection of complex traits in animal models, Nature Genetics, vol.18, pp.19-24, 1998.

J. Demars, S. Fabre, J. Sarry, R. Rossetti, H. Gilbert et al., , 2013.

. Genome-wide, Association Studies Identify Two Novel BMP15 Mutations Responsible for an Atypical Hyperprolificacy Phenotype in Sheep, PLoS Genetics, vol.9, p.1003482

S. C. Fahrenkrug, G. A. Rohrer, B. A. Freking, T. P. Smith, K. Osoegawa et al., A porcine BAC library with tenfold genome coverage: a resource for physical and genetic map integration, Mammalian Genome, vol.12, pp.472-474, 2001.

B. Fan, Z. Du, D. M. Gorbach, and M. F. Rothschild, Development and application of high-density SNP arrays in genomic studies of domestic animals, Asian-Australasian Journal of Animal Sciences, vol.23, pp.833-847, 2010.

B. Fève, Adipogenesis: cellular and molecular aspects, Best Pract. Res. Clin. Endocrinol. Metab, vol.19, pp.483-499, 2005.

O. Filangi, C. Moreno, H. Gilbert, A. Legarra, P. Le-roy et al., QTLMap, a software for QTL detection in outbred populations, Proceedings of the 9th World Congress on Genetics Applied to Livestock Production, 2010.
URL : https://hal.archives-ouvertes.fr/hal-01193540

S. Foissac, P. Bardou, A. Moisan, M. Cros, and T. Schiex, EUGENE'HOM: A generic similarity-based gene finder using multiple homologous sequences, Nucleic Acids Res, vol.31, pp.3742-3745, 2003.

S. Fritz, A. Capitan, A. Djari, S. C. Rodriguez, A. Barbat et al., Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART, SHBG and SLC37A2, PLoS ONE, vol.8, p.65550, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01000118

J. Gellin, G. , and F. , Analyse du génome des espèces d'élevage: projet d'établissement de la carte génétique du porc et des bovins, INRA Prod. Anim, vol.4, pp.97-105, 1991.

M. Georges, Mapping, Fine Mapping, and Molecular Dissection of Quantitative Trait Loci in Domestic Animals, Annual Review of Genomics and Human Genetics, vol.8, pp.131-162, 2007.

M. Gispert, M. Font-i-furnols, M. Gil, A. Velarde, A. Diestre et al., Relationships between carcass quality parameters and genetic types, Meat Science, vol.77, pp.397-404, 2007.

A. González-pérez and N. López-bigas, Improving the Assessment of the Outcome of Nonsynonymous SNVs with a Consensus Deleteriousness Score, Condel. The American Journal of Human Genetics, vol.88, pp.440-449, 2011.

T. Gotoh, E. Albrecht, F. Teuscher, K. Kawabata, K. Sakashita et al., Differences in muscle and fat accretion in Japanese Black and European cattle, Meat Science, vol.82, pp.300-308, 2009.

A. Goureau, Contribution a l'etablissement de la carte genomique comparée entre l'Homme et le Porc (Sus Scrofa domestica), par "coloriage chromosomique, 1997.

A. Goureau, M. Yerle, A. Schmitz, J. Riquet, D. Milan et al., Human and porcine correspondence of chromosome segments using bidirectional chromosome painting, Genomics, vol.36, pp.252-262, 1996.

L. Grobet, L. J. Martin, D. Poncelet, D. Pirottin, B. Brouwers et al., A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle, Nat. Genet, vol.17, pp.71-74, 1997.

F. Guillaume, S. Fritz, D. Boichard, and T. Druet, Estimation by simulation of the efficiency of the French marker-assisted selection program in dairy cattle (Open Access publication), Genetics Selection Evolution, vol.40, pp.91-102, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00894611

O. Harismendy, P. C. Ng, R. L. Strausberg, X. Wang, T. B. Stockwell et al., Evaluation of next generation sequencing platforms for population targeted sequencing studies, Genome Biology, vol.10, p.32, 2009.

F. Hospital, C. Chevalet, and P. Mulsant, Using markers in gene introgression breeding programs, Genetics, vol.132, pp.1199-1210, 1992.

Z. Hu, C. A. Park, and J. M. Reecy, Developmental progress and current status of the Animal QTLdb, Nucleic Acids Research, vol.44, pp.827-833, 2016.

S. J. Humphray, C. E. Scott, R. Clark, B. Marron, C. Bender et al., A high utility integrated map of the pig genome, Genome Biology, vol.8, p.139, 2007.

. Illumina, TruSeq Genotype Ne Reference Guide, vol.30, 2017.

, Mémento de l'éleveur de porc, 2013.

J. T. Jeon, O. Carlborg, A. Törnsten, E. Giuffra, V. Amarger et al., A paternally expressed QTL affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus, Nat. Genet, vol.21, pp.157-158, 1999.

J. T. Jeon, E. W. Park, H. J. Jeon, T. H. Kim, K. T. Lee et al., A large-insert porcine library with sevenfold genome coverage: a tool for positional cloning of candidate genes for major quantitative traits, Mol. Cells, vol.16, pp.113-116, 2003.

W. Jiang, X. Zhao, T. Gabrieli, C. Lou, Y. Ebenstein et al., Cas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters, Nature Communications, vol.6, p.8101, 2015.

P. Kumar, S. Henikoff, and P. C. Ng, Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm, Nature Protocols, vol.4, pp.1073-1081, 2009.

E. S. Lander and D. Botstein, Mapping mendelian factors underlying quantitative traits using RFLP linkage maps, Genetics, vol.121, pp.185-199, 1989.

G. Laval, N. Iannuccelli, C. Legault, D. Milan, M. A. Groenen et al., Genetic diversity of eleven European pig breeds, Genet. Sel. Evol, vol.32, pp.187-203, 2000.
DOI : 10.1051/gse:2000113
URL : https://hal.archives-ouvertes.fr/hal-00894306

L. Dividich, J. Esnault, T. Lynch, B. Hoo-paris, R. Castex et al., Effect of colostral fat level on fat deposition and plasma metabolites in the newborn pig, J. Anim. Sci, vol.69, pp.2480-2488, 1991.

L. Roy, P. Elsen, and J. M. , Principes de l'utilisation des marqueurs génétiques pour la détection des gènes influençant les caractères quantitatifs, INRA Productions Animales, pp.211-215, 2000.

C. Legault, Genetique et Reproduction chez le Porc, Journ Recher Porc, pp.43-60, 1978.

H. Li, B. Handsaker, A. Wysoker, T. Fennell, J. Ruan et al., , p.1000

, The Sequence Alignment/Map format and SAMtools, Genome Project Data Processing Subgroup, vol.25, pp.2078-2079, 2009.

L. Marklund, P. E. Nyström, S. Stern, L. Andersson-eklund, A. et al., Confirmed quantitative trait loci for fatness and growth on pig chromosome 4, Heredity, pp.134-141, 1999.
DOI : 10.1038/sj.hdy.6884630
URL : https://www.nature.com/articles/6884630.pdf

I. L. Mason, A World Dictionary of Livestock Breeds, Types and Varieties, 1988.

A. Mckenna, M. Hanna, E. Banks, A. Sivachenko, K. Cibulskis et al., The Genome Analysis Toolkit: A MapReduce framework for analyzing nextgeneration DNA sequencing data, Genome Research, vol.20, pp.1297-1303, 2010.

A. C. Mcpherron, A. M. Lawler, and S. Lee, Regulation of skeletal muscle mass in mice by a new TGFp superfamily member, Nature, vol.387, pp.83-90, 1997.

C. Médigue, S. Bocs, L. Labarre, C. Mathé, and D. Vallenet, L'annotation in silico des séquences génomiques: Bio-informatique (1), Médecine/Sciences, vol.18, pp.237-250, 2002.

F. Mertes, A. Elsharawy, S. Sauer, J. M. Van-helvoort, P. J. Van-der-zaag et al., Targeted enrichment of genomic DNA regions for next-generation sequencing, Briefings in Functional Genomics, vol.10, pp.374-386, 2011.

D. Milan, N. Woloszyn, M. Yerle, P. Le-roy, M. Bonnet et al., Accurate mapping of the "acid meat" RN gene on genetic and physical maps of pig chromosome 15, Mamm. Genome, vol.7, pp.47-51, 1996.

D. Milan, J. Bidanel, N. Iannuccelli, J. Riquet, Y. Amigues et al., Detection of quantitative trait loci for carcass composition traits in pigs, Genetics Selection Evolution, vol.34, pp.705-728, 2002.
URL : https://hal.archives-ouvertes.fr/hal-00894278

D. Milan, O. Demeure, G. Laval, N. Iannuccelli, C. Genet et al., Identification de régions dugénome répondant à la sélection dans une lignée porcine sinoeuropéenne: la Tai-zumu, Journ Recher Porc, vol.35, pp.309-316, 2003.

G. W. Montgomery, J. A. Sise, P. J. Greenwood, F. , and J. S. , The Booroola F gene mutation in sheep is not located close to the FSH-beta gene, J. Mol. Endocrinol, vol.5, pp.167-173, 1990.

M. Monziols, M. Bonneau, J. Mourot, A. Davenel, and M. Kouba, Les tissus adipeux intermusculaires présentent d'importantes particularités de développement et de composition en comparaison des tissus adipeux sous-cutanés chez le porc, Journées Recherche Porcine, vol.38, pp.61-66, 2006.

P. Mulsant, F. Lecerf, S. Fabre, L. Schibler, P. Monget et al., Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Mérino ewes, Proc. Natl. Acad. Sci. U.S.A, vol.98, pp.5104-5109, 2001.

C. Nezer, L. Moreau, B. Brouwers, W. Coppieters, J. Detilleux et al., An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs, Nat. Genet, vol.21, pp.155-156, 1999.

A. Nygard, C. B. Jørgensen, S. Cirera, and M. Fredholm, Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR, BMC Molecular Biology, vol.8, p.67, 2007.

K. Osoegawa, P. Y. Woon, B. Zhao, E. Frengen, M. Tateno et al., An improved approach for construction of bacterial artificial chromosome libraries, Genomics, vol.52, pp.1-8, 1998.
DOI : 10.1006/geno.1998.5423

J. Ott, Analysis of human genetic linkage, 1999.

M. W. Pfaffl, A new mathematical model for relative quantification in real-time RT-PCR, Nucleic Acids Res, vol.29, p.45, 2001.
DOI : 10.1093/nar/29.9.e45
URL : https://academic.oup.com/nar/article-pdf/29/9/e45/9901003/2900e45.pdf

A. Rafalski, M. , and M. , Corn and humans: recombination and linkage disequilibrium in two genomes of similar size, Trends in Genetics, vol.20, pp.103-111, 2004.

J. Riquet, H. Gilbert, B. Servin, M. Sanchez, N. Iannuccelli et al., , 2011.

, A locally congenic backcross design in pig: a new regional fine QTL mapping approach miming congenic strains used in mouse, BMC Genetics, vol.12, p.6

J. Riquet, M. Mercat, N. Iannuccelli, B. Servin, E. Pailhoux et al., Recherche de causes génétiques des anomalies congénitales majeures chez le porc, vol.7

J. T. Robinson, H. Thorvaldsdóttir, W. Winckler, M. Guttman, E. S. Lander et al., Integrative genomics viewer, Nature Biotechnology, vol.29, pp.24-26, 2011.
DOI : 10.1038/nbt.1754
URL : http://europepmc.org/articles/pmc3346182?pdf=render

C. Rogel-gaillard, N. Bourgeaux, A. Billault, M. Vaiman, and P. Chardon, Construction of a swine BAC library: application to the characterization and mapping of porcine type C endoviral elements, Cytogenet. Cell Genet, vol.85, pp.205-211, 1999.

G. A. Rohrer and J. W. Keele, Identification of quantitative trait loci affecting carcass composition in swine: I. Fat deposition traits, J. Anim. Sci, vol.76, pp.2247-2254, 1998.

M. Sanchez, J. Riquet, N. Iannuccelli, J. Gogue, Y. Billon et al., Programme de cartographie fine de QTL, Journ Recher Porc, vol.35, pp.65-72, 2005.

M. Sanchez, J. Riquet, N. Iannuccelli, J. Gogue, Y. Billon et al., Effects of quantitative trait loci on chromosomes 1, 2, 4, and 7 on growth, carcass, and meat quality traits in backcross Meishan x Large White pigs, Journal of Animal Science, vol.84, pp.526-537, 2006.

M. Sanchez, T. Tribout, N. Iannuccelli, M. Bouffaud, B. Servin et al., Cartographie fine de régions QTL à l'aide de la puce Porcine SNP60 pour l'ingestion, la croissance, la composition de la carcasse et la qualité de la viande en race Large White, 44. Journées de La Recherche Porcine, 2012.

L. Schibler, D. Vaiman, A. Oustry, N. Guinec, A. L. Dangy-caye et al., Construction and extensive characterization of a goat bacterial artificial chromosome library with threefold genome coverage, Mamm. Genome, vol.9, pp.119-124, 1998.

L. Schibler and C. Vaiman, Origine du polymorphisme de l'ADN. INRA Prod. Anim, 2000.

S. Schwob, J. Riquet, T. Bellec, L. Kernaleguen, T. Tribout et al., Mise en place d'un programme de sélection assistée par marqueurs dans la population sino-européenne Duochan, Journées Rech. Porcine, vol.41, pp.29-30, 2009.

B. Servin, T. Faraut, N. Iannuccelli, D. Zelenika, M. et al., High-resolution autosomal radiation hybrid maps of the pig genome and their contribution to the genome sequence assembly, BMC Genomics, vol.13, p.585, 2012.

K. Suzuki, S. Asakawa, M. Iida, S. Shimanuki, N. Fujishima et al., Construction and evaluation of a porcine bacterial artificial chromosome library, Anim. Genet, vol.31, pp.8-12, 2000.

D. Thierry-mieg and J. Thierry-mieg, AceView: a comprehensive cDNA-supported gene and transcripts, 2006.

, Genome Biology, vol.7, p.12

F. Tortereau, B. Servin, L. Frantz, H. Megens, D. Milan et al., A high density recombination map of the pig reveals a correlation between sexspecific recombination and GC content, BMC Genomics, vol.13, p.586, 2012.

P. Trayhurn, N. J. Temple, and J. Van-aerde, Evidence from immunoblotting studies on uncoupling protein that brown adipose tissue is not present in the domestic pig. Can, J. Physiol. Pharmacol, vol.67, pp.1480-1485, 1989.

T. Tribout, Intérêt de la sélection génomique dans les programmes de sélection porcins: cas d'une lignée mâle de grande taille, 2013.

,. Van-laere, M. Nguyen, M. Braunschweig, C. Nezer, C. Collette et al., A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig, Nature, vol.425, pp.832-836, 2003.

A. Vignal, D. Milan, M. Sancristobal, and A. Eggen, A review on SNP and other types of molecular markers and their use in animal genetics, Genetics Selection Evolution, vol.34, pp.275-305, 2002.
URL : https://hal.archives-ouvertes.fr/hal-00894413

H. Visscher, H. Brinkhuis, D. L. Dilcher, W. C. Elsik, Y. Eshet et al., , 1996.

, The terminal Paleozoic fungal event: evidence of terrestrial ecosystem destabilization and collapse, Proc. Natl. Acad. Sci. U.S.A, vol.93, pp.2155-2158

M. Yerle, P. Pinton, A. Robic, A. Alfonso, Y. Palvadeau et al., Construction of a whole-genome radiation hybrid panel for high-resolution gene mapping in pigs, Cytogenet. Cell Genet, vol.82, pp.182-188, 1998.

M. Yerle, P. Pinton, C. Delcros, N. Arnal, D. Milan et al., Generation and characterization of a 12,000-rad radiation hybrid panel for fine mapping in pig, Cytogenet. Genome Res, vol.97, pp.219-228, 2002.

C. Zhu, M. Gore, E. S. Buckler, Y. , and J. , Status and Prospects of Association Mapping in Plants, The Plant Genome Journal, vol.1, p.5, 2008.