Accéder directement au contenu Accéder directement à la navigation

Genetic factors affecting milk composition in goats

Abstract : Research on genetic factors affecting milk composition in goats has focused mainly on casein polymorphisms while loci involved in lipid metabolism have not been studied in depth. We have used a candidate gene pproach aimed to characterize the polymorphism of the lipoprotein lipase (LPL), Acetyl-coenzyme A carboxylase α (ACACA) and Acyl-Coenzyme A: diacylglycerol acyltransferase 1 (DGAT1) genes. Association analyses between the LPL and ACACA genes and milk traits in the Murciano-Granadina goat breed were carried out. Moreover, we have a used functional genomics approach to investigate the consequences of casein retention in the endoplasmic reticulum of mammary epithelial cells with CSN1S1 defective genotypes. The LPL and ACACA genes were characterized in 18 goats belonging to three Spanish breeds. The goat LPL cDNA coding sequence was 2,657 bp long, encoding a protein of 478 amino acids. This sequence included part of the 5’UTR (403 bp) and 3’UTR (817 bp) plus the coding sequence (1,437 bp). Two single nucleotide polymorphisms (SNP) were detected in the goat LPL cDNA sequence: a G50C missense mutation, which involved a Ser→ Thr amino acid replacement at position 17, and a T2094C substitution in the 3’UTR. The partial ACACA cDNA sequence was 5.5 kb and encoded 1,832 amino acids. One SNP was identified at exon 45 (C5493T). The genotyping of these three SNP in diverse goat breeds revealed that they are segregating in most of the analysed populations. A univariate mixed model was used to evaluate the association between LPL and ACACA genotypes and fourteen milk traits, with four available records each one, that were registered during one lactation in 130 Murciano-Granadina goats. The G50C SNP was suggestively associated with fat yield (P < 0.05) and tended to affect the milk dry weight basis (P = 0.07). The LPL T2094C SNP was not associated with any of the measured traits. The ACACA C5493T SNP was suggestively associated with fat yield (P = 0.02), lactose content (P = 0.01) and somatic cell content (P = 0.03). In addition, we have sequenced a 1,552 bp fragment of the DGAT1 cDNA in nine goat breeds, which encompasses most of the coding sequence (from exon 1 to 17), and a genomic fragment covering exons 12 to 17. One SNP involving a T to C substitution at intron 16 was detected. The genotyping of this SNP revealed that the C variant is a minority allele with frequencies ranging from 0.062 (Murciano-Granadina) to 0.109 (Malagueña). The performance of an association analysis between DGAT1 genotypes and milk traits is still pending. The CSN1S1 genotype has been shown to have a deep influence on milk quality being strongly related with the amounts of proteins and lipids that are secreted into milk. Individuals with low amounts of CSN1S1 in their milk are characterized, amongst other features, by the retention of caseins in the rough endoplasmic reticulum (RER) of mammary epithelial cells (MEC). A second major goal of this thesis was to investigate if this retention of caseins in the RER of MEC with defective CSN1S1 genotypes involves changes in gene expression at the mRNA and protein levels. In this way, we have shown that binding immunoglobulin protein (BiP), a chaperone deeply involved in protein folding and quality control, is overexpressed in the RER of MEC with OO CSN1S1 genotypes when compared with AA cells. This finding suggested that MEC with null CSN1S1 genotypes develop an unfolded protein response (UPR) as a consequence of casein retention in the RER. Our finding that the spliced isoform of X-box binding prootein 1 (XBP1) has an increased expression in these cells suggests the implication of the Inositol requirement 1 (IRE1) pathway in the development of the UPR. Since the development of an UPR via XBP1 usually produces an increase of phosphatidylcholine biosynthesis, we have evaluated if CSN1S1 genotype influences choline cytidylyltransferase (CCT) activity. Although our data did not reach statistical significance, we found an increased CCT activity in cells with OO genotypes. This feature can be explained in the context of the increased ER membrane synthesis that usually concurs with the establishment of an UPR. The comparison of the transcriptomic profiles corresponding to MEC with AA and OO CSN1S1 genotypes allowed us to demonstrate that casein retention in the MEC of RER causes a significant alteration on gene expression mainly those related with protein folding, secretion and translocation.
Mots-clés : GENETIQUE
Type de document :
Liste complète des métadonnées
Déposant : Migration Prodinra <>
Soumis le : samedi 6 juin 2020 - 22:53:17
Dernière modification le : vendredi 12 juin 2020 - 10:43:26


  • HAL Id : tel-02824674, version 1
  • PRODINRA : 34824



Bouabid Badaoui. Genetic factors affecting milk composition in goats. Life Sciences [q-bio]. AgroParisTech; Universitat Autònoma de Barcelona (Barcelona), 2008. English. ⟨tel-02824674⟩



Consultations de la notice