| 1. |
- Duchemin, Sandrine
(author)
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A quantitative trait locus on Bos taurus autosome 17 explains a large proportion of the genetic variation in de novo synthesized milk fatty acids
- 2014
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In: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 97, s. 7276-7285
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Journal article (peer-reviewed)abstract
- A genomic region associated with milk fatty acid (FA) composition has been detected on Bos taurus autosome (BTA)17 based on 50,000 (50K) single nucleotide polymorphism (SNP) genotypes. The aim of our study was to fine-map BTA17 with imputed 777,000 (777K) SNP genotypes to identify candidate genes associated with milk FA composition. Phenotypes consisted of gas chromatography measurements of 14 FA based on winter and summer milk samples. Phenotypes and genotypes were available on 1,640 animals in winter milk, and on 1,581 animals in summer milk samples. Single-SNP analyses showed that several SNP in a region located between 29.0 and 34.0 Mbp were in strong association with C6:0, C8:0, and C10:0. This region was further characterized based on haplotypes. In summer milk samples, for example, these haplotypes explained almost 10% of the genetic variance in C6:0, 9% in C8:0, 3.5% in C10:0, 1.8% in C12:0, and 0.9% in C14:0. Two groups of haplotypes with distinct predicted effects could be defined, suggesting the presence of one causal variant. Predicted haplotype effects tended to increase from C6:0 to C14:0; however, the proportion of genetic variance explained by the haplotypes tended to decrease from C6:0 to C14:0. This is an indication that the quantitative trait locus (QTL) region is involved either in the elongation process or in early termination of de novo synthesized FA. Although many genes are present in this QTL region, most of these genes on BTA17 have not been characterized yet. The strongest association was found close to the progesterone receptor membrane component 2 (PGRMC2) gene, which has not yet been associated with milk FA composition. Therefore, no clear candidate gene associated with milk FA composition could be identified for this QTL.
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| 2. |
- Duchemin, Sandrine
(author)
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Fine-mapping of a candidate region associated with milk-fat composition on Bos Taurus Autosome 17
- 2014
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Conference paper (other academic/artistic)abstract
- A genomic region associated with milk-fat composition has been detected on BTA17. However, no candidate gene or causal variant has been identified so far. Our goal was to fine-map this region by using imputed 777k SNP genotypes. Phenotypes and genotypes were available on 1,581 animals. Phenotypes consisted of gas chromatography measurements of C8:0, and genotypes consisted of the imputed 777k SNP. Single SNP analyses were run using an animal model to retrieve significant SNP. Based on these SNP, haplotypes were constructed. Haplotypes suggested the presence of one QTL within the fine-mapped region. This QTL explained 9% of the genetic variation in C8:0. Although many genes are present in this QTL region, most of these genes have not been characterized yet. Therefore, no clear candidate gene associated with milk-fat composition could be identified.
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| 3. |
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| 4. |
- Duchemin, Sandrine
(author)
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Fine-mapping of BTA17 using imputed sequences for associations with de novo synthesized fatty acids in bovine milk
- 2017
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In: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 100, s. 9125-9135
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Journal article (peer-reviewed)abstract
- The aim of this study was to fine-map a genomic region associated with milk fatty acids (FA) on Bos taurus autosome (BTA) 17. This genomic region has been discovered with 50,000 (50k) single nucleotide polymorphisms (SNP) imputed to 777,000 (777k) SNP. In this study, high-density genotypes were imputed to whole-genome sequences level to identify candidate gene(s) associated with milk FA composition on BTA17. Phenotypes and genotypes were available for 1,640 cows sampled in winter, and for 1,581 cows sampled in summer. Phenotypes consisted of gas chromatography measurements in winter and in summer milk samples of 6 individual FA and the indicator of de novo synthesis, C6:0-C14:0. Genotypes consisted of imputed 777k SNP, and 89 sequenced ancestors of the population of genotyped cows. In addition, 450 whole-genome sequences from the 1,000 Bull Genome Consortium were available. Using 495 Holstein-Friesian sequences as a reference population, the 777k SNP genotypes of the cows were imputed to sequence level. We then applied single-variant analyses with an animal model, and identified thousands of significant associations with C6:0, C8:0, C10:0, C12:0, C14:0, and C6:0 C14:0. For C8:0 in summer milk samples, the genomic region located between 29 and 34 Mbp on BTA17 revealed a total of 646 significant associations. The most significant associations [ -log(10)(P-value) = 7.82] were 8 SNP in perfect linkage disequilibrium. After fitting one of these 8 SNP as a fixed effect in the model, and re-running the single variant analyses, no further significant associations were found for any of the 6 FA or C6:0 C14:0. These findings suggest that one polymorphism underlying this QTL on BTA17 influences multiple de novo synthesized milk FA. Thirteen genes in the QTL region were identified and analyzed carefully. Six out of the 8 SNP that showed the strongest associations were located in the La ribonucleoprotein domain family, member 1B (LARP1B) gene, and we suggest LARP1B as a primary candidate gene. Another gene of interest for this QTL region might be PKE4. None of these suggested candidate genes have previously been associated with milk fat synthesis or milk FA composition.
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| 5. |
- Duchemin, Sandrine, et al.
(author)
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Genetic parameters for noncoagulating milk, milk coagulation properties, and detailed milk composition in Swedish Red Dairy Cattle
- 2020
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In: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 103:9, s. 8330-8342
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Journal article (peer-reviewed)abstract
- The rennet-induced coagulation ability of milk is important in cheese production. For Swedish Red Dairy Cattle (RDC), this ability is reduced because of a high prevalence of noncoagulating (NC) milk. In this study, we simultaneously combined genetic parameters for NC milk, milk coagulation properties, milk composition, physical traits, and milk protein composition. Our aim was to estimate heritability and genetic and phenotypic correlations for NC milk and 24 traits (milk coagulation properties, milk composition, physical traits, and milk protein composition). Phenotypes and ~7,000 SNP genotypes were available for all 600 Swedish RDC. The genotypes were imputed from ~7,000 SNP to 50,000 SNP. Variance components and genetic parameters were estimated with an animal model. In Swedish RDC, a moderate heritability estimate of 0.28 was found for NC milk. For the other 24 traits, heritability estimates ranged from 0.12 to 0.77 (standard errors from 0.08 to 0.18). A total of 300 phenotypic and genetic correlations were estimated. For phenotypic and genetic correlations, 172 and 95 were significant, respectively. In general, most traits showing significant genetic correlations also showed significant phenotypic correlations. In this study, phenotypic and genetic correlations with NC milk suggest that many correlations between traits exist, making it difficult to predict the real consequences on the composition of milk, if selective breeding is applied on NC milk. We speculate that some of these consequences may lead to changes in the composition of milk, most likely affecting its physical and organoleptic properties. However, our results suggest that κ-casein could be used as an indicator trait to predict the occurrence of NC milk at the herd level.
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| 6. |
- Duchemin, Sandrine
(author)
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Genome-wide association study for alpha(S1)- and( )alpha(S2) -casein phosphorylation in Dutch Holstein Friesian
- 2019
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In: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 102, s. 1374-1385
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Journal article (peer-reviewed)abstract
- Phosphorylation of caseins (CN) is a crucial post-translational modification that allows caseins to form colloid particles known as casein micelles. Both alpha(S1)-and alpha(S2)-CN show varying degrees of phosphorylation (isoforms) in cow milk and were suggested to be more relevant for stabilizing internal micellar structure than beta- and kappa-CN. However, little is known about the genetic background of individual alpha(S2)-CN phosphorylation isoforms and the phosphorylation degrees of alpha(S1)- and alpha(S2)-CN (alpha(S1)-CN PD and alpha(S2)-CN PD), defined as the proportion of isoforms with higher degrees of phosphorylation in total alpha(S1)- and alpha(S2)-CN, respectively. We aimed to identify genomic regions associated with these traits using 50K single nucleotide polymorphisms for 1,857 Dutch Holstein Friesian cows. A total of 10 quantitative trait loci (QTL) regions were identified for all studied traits on 10 Bos taurus autosomes (BTA1, 2, 6, 9, 11, 14, 15, 18, 24, and 28). Regions associated with multiple traits were found on BTA1, 6, 11, and 14. We showed 2 QTL regions on BTA1, one affecting alpha(S2)-CN production and the other harboring the SLC37A I gene, which encodes a phosphorus antiporter and affects alpha(S1)-and alpha(S2)-CN PD. The QTL on BTA6 harbors the casein gene cluster and affects individual alpha(S1)-CN phosphorylation isoforms. The QTL on BTA11 harbors the PAEP gene that encodes for beta-lactoglobulin and affects relative concentrations of alpha(S2)-CN-10P and alpha(S2)-CN-11P as well as alpha(S1)-CN PD and alpha(S1)-CN PD. The QTL on BTA14 harbors the DGAT1 gene and affects relative concentrations of alpha(S1)-CN-10P and alpha(S2)-CN-11P as well as alpha(S1)-CN PD and alpha(S2)-CN PD. Our results suggest that effects of identified genomic regions on phosphorylation of alpha(S1)-CN and alpha(S2)-CN are related to changes in milk synthesis and phosphorus secretion in milk. The actual roles of SLC37A1, PAEP, and DGAT1 in alpha(S1)- and alpha(S2)- phosphorylation in Dutch Holstein Friesian require further investigation.
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| 7. |
- Duchemin, Sandrine, et al.
(author)
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Identification of QTL on chromosome 18 associated with non-coagulating milk in Swedish Red cows
- 2016
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In: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 7
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Journal article (peer-reviewed)abstract
- Non-coagulating (NC) milk, defined as milk not coagulating within 40 min after rennet-addition, can have a negative influence on cheese production. Its prevalence is estimated at 18% in the Swedish Red (SR) cow population. Our study aimed at identifying genomic regions and causal variants associated with NC milk in SR cows, by doing a GWAS using 777k SNP genotypes and using imputed sequences to fine map the most promising genomic region. Phenotypes were available from 382 SR cows belonging to 21 herds in the south of Sweden, from which individual morning milk was sampled. NC milk was treated as a binary trait, receiving a score of one in case of non-coagulation within 40 min. For all 382 SR cows, 777k SNP genotypes were available as well as the combined genotypes of the genetic variants of as1-β-κ-caseins. In addition, whole-genome sequences from the 1000 Bull Genome Consortium (Run 3) were available for 429 animals of 15 different breeds. From these sequences, 33 sequences belonged to SR and Finish Ayrshire bulls with a large impact in the SR cow population. Single-marker analyses were run in ASReml using an animal model. After fitting the casein loci, 14 associations at -Log10(P-value) > 6 identified a promising region located on BTA18. We imputed sequences to the 382 genotyped SR cows using Beagle 4 for half of BTA18, and ran a region-wide association study with imputed sequences. In a seven mega base-pairs region on BTA18, our strongest association with NC milk explained almost 34% of the genetic variation in NC milk. Since it is possible that multiple QTL are in strong LD in this region, 59 haplotypes were built, genetically differentiated by means of a phylogenetic tree, and tested in phenotype-genotype association studies. Haplotype analyses support the existence of one QTL underlying NC milk in SR cows. A candidate gene of interest is the VPS35 gene, for which one of our strongest association is an intron SNP in this gene. The VPS35 gene belongs to the mammary gene sets of pre-parturient and of lactating cows.
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| 8. |
- Duchemin, Sandrine
(author)
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Mapping and fine-mapping of genetic factors affecting bovine milk composition
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Bovine milk is an important source of nutrients in Western diets. Unraveling the genetic background of bovine milk composition by finding genes associated with milk-fat composition and non-coagulation of milk were the main goals of this thesis. In Chapter 1, a brief description of phenotypes and genotypes used throughout the thesis is given. In Chapter 2, I calculated the genetic parameters for winter and summer milk-fat composition from ~2,000 Holstein-Friesian cows, and concluded that most of the fatty acids (FA) can be treated as genetically the same trait. The main differences between milk-fat composition between winter and summer milk samples are most likely due to differences in diets. In Chapter 3, I performed genome-wide association studies (GWAS) with imputed 777,000 single nucleotide polymorphism (SNP) genotypes. I targeted a quantitative trait locus (QTL) region on Bos taurus autosome (BTA) 17 previously identified with 50,000 SNP genotypes, and identified a region covering 5 mega-base pairs on BTA17 that explained a large proportion of the genetic variation in de novo synthesized milk FA. In Chapter 4, the availability of whole-genome sequences of keys ancestors of our population of cows allowed to fine-mapped BTA17 with imputed sequences. The resolution of the 5 mega base-pairs region substantially improved, which allowed the identification of the LA ribonucleoprotein domain family, member 1B (LARP1B) gene as the most likely candidate gene associated with de novo synthesized milk FA on BTA17. The LARP1B gene has not been associated with milk-fat composition before. In Chapter 5, I explored the genetic background of non-coagulation of bovine milk. I performed a GWAS with 777,000 SNP genotypes in 382 Swedish Red cows, and identified a region covering 7 mega base-pairs on BTA18 strongly associated with noncoagulation of milk. This region was further characterized by means of fine-mapping with imputed sequences. In addition, haplotypes were built, genetically differentiated by means of a phylogenetic tree, and tested in phenotype-genotype association studies. As a result, I identified the vacuolar protein sorting 35 homolog, mRNA (VPS35) gene, as candidate. The VPS35 gene has not been associated to milk composition before. In Chapter 6, the general discussion is presented. I start discussing the challenges with respect to high-density genotypes for gene discovery, and I continue discussing future possibilities to expand gene discovery studies, with which I propose some alternatives to identify causal variants underlying complex traits in cattle.
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| 9. |
- Nilsson, Kajsa, et al.
(author)
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Characterisation of non-coagulating milk and effects of milk composition and physical properties on rennet-induced coagulation in Swedish Red Dairy Cattle
- 2019
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In: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 95, s. 50-57
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Journal article (peer-reviewed)abstract
- Non-coagulating milk is a serious problem in the cheese industry, since it decreases cheese yield, resulting in decreased economic output. This study evaluated rennet-induced coagulation properties and composition of milk from individual Swedish Red Dairy Cattle. Milk samples from 679 individual cows were rheologically evaluated, of which 18.1% of the cows produced non-coagulating milk and 18.9% produced poor-coagulating milk. This resulted in 37% of the milk samples being non-optimal in cheese production, which is an alarmingly high figure. A comparison between non-coagulating and coagulating milk showed a significantly lower calcium content and less free Ca 2+ in non-coagulating milk. The results provide more information about non- and poor-coagulating milk and will be further used to understand the genetic background of non-coagulating milk and breed against this undesired milk property.
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| 10. |
- Nilsson, K., et al.
(author)
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Effects of milk proteins and posttranslational modifications on noncoagulating milk from Swedish Red dairy cattle
- 2020
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In: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 103:8, s. 6858-6868
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Journal article (peer-reviewed)abstract
- Milk that does not coagulate after rennet addition, also called noncoagulating (NC) milk, is unwanted in cheese production due to prolonged processing time. Amounts of whey and casein proteins, genetic variants, as well as posttranslational modifications (PTM) of proteins are all contributing factors in rennet-induced coagulation of milk. In this study, we conducted a wide-ranging investigation of milk proteins in milk samples from 616 Swedish Red dairy cattle using liquid chromatography-high resolution mass spectrometry. Relative concentration of proteins, genetic variants, and PTM were compared between NC milk and coagulating milk. The PTM investigated were phosphorylation of caseins and glycosylation of κ-casein. Several genetic variants and PTM were found, including rare phosphorylation variants of the αS-caseins. Genetic variants were found to effect the expressed amount of different proteins. Further, the effect of protein amounts and PTM on a binary NC milk trait was modeled using a generalized linear model. The model showed that NC milk significantly correlated with higher relative concentrations of α-lactalbumin and β-casein and lower relative concentrations of β-lactoglobulin and κ-casein. Regarding PTM of caseins, an effect on NC milk from a lower relative concentration of αS1-casein with 8 phosphate groups were found, even though an effect from total relative concentration of αS1-casein was not found. This study has provided insights into protein variants and PTM important for NC milk to improve this undesirable property.
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| 11. |
- Nyman, Sofia, et al.
(author)
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Genome-wide association study of normal and atypical progesterone profiles in Holstein-Friesian dairy cows
- 2019
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In: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 102, s. 3204-3215
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Journal article (peer-reviewed)abstract
- Female fertility has a major role in dairy production and affects the profitability of dairy cattle. The genetic progress obtained by traditional selection can be slow because of the low heritability of classical fertility traits. Endocrine fertility traits based on progesterone concentration in milk have higher heritability and more directly reflect the cow's own reproductive physiology. The aim of our study was to identify genomic regions for 7 endocrine fertility traits in dairy cows by performing a genome-wide association study with 54,000 SNP. The next step was to fine-map targeted genomic regions with significant SNP using imputed sequences to identify potential candidate genes associated with the normal and atypical progesterone profiles. The association between a SNP and a phenotype was assessed by a single SNP analysis, using a linear mixed model that included a random polygenic effect. Phenotypes and genotypes were available for 1,126 primiparous and multiparous Holstein-Friesian cows from research herds in Ireland, the Netherlands, Sweden, and the United Kingdom. In total, 44 significant SNP associated with 7 endocrine fertility traits were identified on .Bos taurus autosome (BTA) 1-4, 6, 8-9, 11-12, 14-17, 19, 21-24, and 29. Three chromosomes, BTA8, BTA17, and BTA23, were imputed from 54,000 SNP genotypes to the whole-genome sequence level with Beagle version 4.1. The fine-mapping identified several significant associations with delayed cyclicity, cessation of cyclicity, commencement of luteal activity, and inter-ovulatory interval. These associations may contribute to an index of markers for genetic improvement of fertility. Several potential candidate genes reported to affect reproduction were also identified in the targeted genomic regions. However, due to high linkage disequilibrium, it was not possible to identify putative causal genes or polymorphisms for any of the regions.
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| 12. |
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