Identification of quantitative trait loci underlying milk traits in Spanish dairy sheep using linkage plus combined linkage disequilibrium and linkage analysis approaches

In this study, 2 procedures were used to analyze a data set from a whole-genome scan, one based on linkage analysis information and the other combing linkage disequilibrium and linkage analysis (LDLA), to determine the quantitative trait loci (QTL) influencing milk production traits in sheep. A total of 1,696 animals from 16 half-sib families were genotyped using the OvineSNP50 BeadChip (Illumina Inc., San Diego, CA) and analysis was performed using a daughter design. Moreover, the same data set has been previously investigated through a genome-wide association (GWA) analysis and a comparison of results from the 3 methods has been possible. The linkage analysis and LDLA methodologies yielded different results, although some significantly associated regions were common to both procedures. The linkage analysis detected 3 overlapping genome-wise significant QTL on sheep chromosome (OAR) 2 influencing milk yield, protein yield, and fat yield, whereas 34 genome-wise significant QTL regions were detected using the LDLA approach. The most significant QTL for protein and fat percentages was detected on OAR3, which was reported in a previous GWA analysis. Both the linkage analysis and LDLA identified many other chromosome-wise significant associations across different sheep autosomes. Additional analyses were performed on OAR2 and OAR3 to determine the possible causality of the most significant polymorphisms identified for these genetic effects by the previously reported GWA analysis. For OAR3, the analyses demonstrated additional genetic proof of the causality previously suggested by our group for a single nucleotide polymorphism located in the α-lactalbumin gene (LALBA). In summary, although the results shown here suggest that in commercial dairy populations, the LDLA method exhibits a higher efficiency to map QTL than the simple linkage analysis or linkage disequilibrium methods, we believe that comparing the 3 analysis methods is the best approach to obtain a global picture of all identifiable QTL segregating in the population at both family-based and population-based levels.     

A genome scan for quantitative trait loci affecting body conformation traits in Spanish Churra dairy sheep

A genome scan for chromosomal regions influencing body conformation traits was conducted for a population of Spanish Churra dairy sheep following a daughter design. A total of 739 ewes from 11 half-sib sire families were included in the study. The ewes were scored for the 5 linear traits used in the breeding scheme of the Churra breed to assess body conformation: stature, rear legs-rear view, foot angle, rump width, and general appearance. All the animals, including the 11 sires, were genotyped for 181 microsatellite markers evenly distributed across the 26 sheep autosomes. Using the yield deviations of the raw scores adjusted for fixed factors as phenotypic measurements, a quantitative trait loci (QTL) analysis was performed on the basis of a multi-marker regression method. Seven suggestive QTL were identified on chromosomes Ovis aries (OAR)2, OAR5, OAR16, OAR23, and OAR26, but none reached a genome-wise significance level. Putative QTL were identified for all of the traits analyzed, except for general appearance score. The suggestive QTL showing the highest test statistic influenced rear legs-rear view and was localized on OAR16, close to the growth hormone receptor coding gene, GHR. Some of the putative linkage associations reported here are consistent with previously reported QTL in cattle for similar traits. To the best of our knowledge, this study provides the first report of QTL for body conformation traits in dairy sheep; further studies will be needed to confirm and redefine the linkage associations reported herein. It is expected that future genome-wide association analyses of larger families will help identify genes underlying these putative genetic effects and provide useful markers for marker-assisted selection of such functional traits.     

Short communication: detection of quantitative trait loci influencing somatic cell score in Spanish Churra sheep

Eleven half-sib ovine families, including 1,421 Spanish Churra ewes, were analyzed for 181 microsatellite markers spanning the entire autosomic ovine genome. Using a multimarker regression method, a daughter experimental design was used to identify putative quantitative trait loci (QTL) affecting the somatic cell score (SCS). Chromosome-wise significance thresholds were set empirically by permuting the phenotypic data. Marker order and genetic distances of the autosomic linkage map built for this commercial population were in accordance with the published ovine linkage map. An across-family association analysis revealed a region on chromosome 20 suggestive of evidence for a QTL. Segregation of the QTL into 2 families was inferred from the within-family analysis, and differences in the position of the suggested QTL were found between the 2 half-sib groups. This could be the result of incomplete information associated with the markers for the significant families. The location of the major histocompatibility complex in proximity to the across-family effect suggests this region may harbor a segregating QTL for the SCS in the Churra population. Studies in dairy cattle examining the SCS have reported linkage associations on corresponding bovine orthologous regions, supporting the validity of our findings.     

Identification of functional candidate variants and genes for feed efficiency in Holstein and Jersey cattle breeds using RNA-sequencing

The identification of functional genetic variants and associated candidate genes linked to feed efficiency may help improve selection for feed efficiency in dairy cattle, providing economic and environmental benefits for the dairy industry. This study used RNA-sequencing data obtained from liver tissue from 9 Holstein cows [n = 5 low residual feed intake (RFI), n = 4 high RFI] and 10 Jersey cows (n = 5 low RFI, n = 5 high RFI), which were selected from a single population of 200 animals. Using RNA-sequencing, 3 analyses were performed to identify: (1) variants within low or high RFI Holstein cattle; (2) variants within low or high RFI Jersey cattle; and (3) variants within low or high RFI groups, which are common across both Holstein and Jersey cattle breeds. From each analysis, all variants were filtered for moderate, modifier, or high functional effect, and co-localized quantitative trait loci (QTL) classes, enriched biological processes, and co-localized genes related to these variants, were identified. The overlapping of the resulting genes co-localized with functional SNP from each analysis in both breeds for low or high RFI groups were compared. For the first two analyses, the total number of candidate genes associated with moderate, modifier, or high functional effect variants fixed within low or high RFI groups were 2,810 and 3,390 for Holstein and Jersey breeds, respectively. The major QTL classes co-localized with these variants included milk and reproduction QTL for the Holstein breed, and milk, production, and reproduction QTL for the Jersey breed. For the third analysis, the common variants across both Holstein and Jersey breeds, uniquely fixed within low or high RFI groups were identified, revealing a total of 86,209 and 111,126 functional variants in low and high RFI groups, respectively. Across all 3 analyses for low and high RFI cattle, 12 and 31 co-localized genes were overlapping, respectively. Among the overlapping genes across breeds, 9 were commonly detected in both the low and high RFI groups (INSRR, CSK, DYNC1H1, GAB1, KAT2B, RXRA, SHC1, TRRAP, PIK3CB), which are known to play a key role in the regulation of biological processes that have high metabolic demand and are related to cell growth and regeneration, metabolism, and immune function. The genes identified and their associated functional variants may serve as candidate genetic markers and can be implemented into breeding programs to help improve the selection for feed efficiency in dairy cattle.     

Detection of quantitative trait loci affecting the milk fatty acid profile on sheep chromosome 22: Role of the stearoyl-CoA desaturase gene in Spanish Churra sheep

Sheep milk fat contains several components that may provide human health benefits, such as monounsaturated fatty acids and conjugated linoleic acid (CLA). Most of the CLA in ruminant milk is synthesized in the mammary gland by the action of the enzyme stearoyl-CoA desaturase (SCD) on circulating vaccenic acid (trans-11 C18:2; VA). Previous studies have found significant associations between polymorphisms in the SCD gene and the fatty acid composition of ruminant products, including sheep milk. Based on this, we performed a quantitative trait loci (QTL) analysis of an ovine chromosome (22) that harbors the SCD gene for effects on milk fatty acid composition traits and classical milk production traits. We identified a suggestive QTL influencing the CLA/VA ratio with the maximum statistic at position 26 cM of the studied chromosome, whereas the SCD gene has been mapped to position 41.6 cM. The individual introduction of 4 SCD single nucleotide polymorphisms in the QTL model did not cause a reduction of the variance explained by the QTL, which suggests that the SCD gene is not directly responsible for the detected effect in the Churra population studied herein. This conclusion was supported by the lack of any significant association identified between the 4 SCD single nucleotide polymorphisms and the CLA/VA ratio. This association analysis suggested a possible effect of the SCD gene on milk fat percentage in Churra sheep. An independent confirmation of these primary results will be required before attempting its practical implementation in selection programs.     

Short communication: Replication of genome-wide association studies for milk production traits in Chinese Holstein by an efficient rotated linear mixed model

Milk is regarded as an important nutrient for humans, and Chinese Holstein cows provide high-quality milk for billions of Chinese people. Therefore, detecting quantitative trait nucleotides (QTN) or candidate genes for milk production traits in Chinese Holstein is important. In this study, we performed genome-wide association studies (GWAS) in a Chinese Holstein population of 6,675 cows and 71,633 SNP using deregressed proofs (DRP) as phenotypes to replicate our previous study in a population of 1,815 cows and 39,163 SNP using estimated breeding values (EBV) as phenotypes. The associations between 3 milk production traits—milk yield (MY), fat percentage (FP), and protein percentage (PP)—and the SNP were determined by using an efficient rotated linear mixed model, which benefits from linear transformations of genomic estimated values and Eigen decomposition of the genomic relationship matrix algorithm. In total, we detected 94 SNP that were significantly associated with one or more milk production traits, including 7 SNP for MY, 76 for FP, and 36 for PP; 87% of these SNP were distributed across Bos taurus autosomes 14 and 20. In total, 83 SNP were found to be located within the reported quantitative trait loci (QTL) regions, and one novel segment (between 1.41 and 1.49 Mb) on chromosome 14 was significantly associated with FP, which could be an important candidate QTL region. In addition, the detected intervals were narrowed down from the reported regions harboring causal variants. The top significant SNP for the 3 traits was ARS-BFGL-NGS-4939, which is located within the DGAT1 gene. Five detected genes (CYHR1, FOXH1, OPLAH, PLEC, VPS28) have effects on all 3 traits. Our study provides a suite of QTN, candidate genes, and a novel QTL associated with milk production traits, and thus forms a solid basis for genomic selection and molecular breeding for milk production traits in Chinese Holstein.     

Joint analysis of quantitative trait loci for clinical mastitis and somatic cell score on five chromosomes in three Nordic dairy cattle breeds

Five chromosomes were selected for joint quantitative trait loci (QTL) analyses for clinical mastitis (CM) and somatic cell score (SCS) in 3 breeds: Finnish Ayrshire (FA), Swedish Red and White (SRB), and Danish Red (DR). In total, 19 grandsires and 672 sons in FA, 19 grandsires and 499 sons in SRB, and 8 grandsires and 258 sons in DR were used in the study. These individuals were genotyped with the 61 microsatellite markers used in any of the previous QTL scans on the selected chromosomes. Within-family QTL analyses based on linear regression models were carried out for CM and SCS to identify the segregating sires for each region. On the segregating families, joint single-trait and 2-trait analyses were performed using variance components models. The analyses confirmed that QTL affecting CM or SCS, or both, segregate on Bos taurus autosomes (BTA) 9, 11, 14, and 18, whereas a QTL on BTA29 could not be confirmed. Our results indicate that there may be at least 2 linked QTL on BTA9, one that primarily affects CM and a second that primarily affects SCS. On chromosomes BTA11, 14, and 18, the joint analyses were only significant for SCS.     

Genome-wide association study for age at puberty and resumption of cyclicity in a crossbred dairy cattle population

Fertility is of primary economic importance in dairy cattle and the most common reason for involuntary culling. However, standard fertility traits have very low heritability that renders genetic selection slow and difficult. In this study, we explored fertility from an endocrine standpoint. A total of 1,163 crossbred Holstein-Normande females in a 3-generation familial design were studied for progesterone level measured every 10 d to determine age at puberty (PUB) and commencement of postpartum luteal activity (CPLA). Genetic parameters were estimated using REML with WOMBAT software. The heritability estimates were 0.38 ± 0.10 and 0.16 ± 0.07 for PUB and CPLA, respectively. Moreover, the 2 traits were genetically correlated (0.45 ± 0.23), suggesting a partially common determinism. Because of the family structure, a linkage disequilibrium and linkage analysis approach was preferred over standard genome-wide association study to map genomic regions associated with these traits. Ten quantitative trait loci (QTL) were detected for PUB on chromosomes 1, 3, 11, 13, 14, 21, and 29, whereas 3 QTL were associated with CPLA on chromosomes 21 and 26. Only the QTL on chromosome 21 was common to both traits. Four functional candidate genes (NCOA2, GAS2, OVOL1, and FOSL1) were identified in the detected regions. These findings will contribute to a clearer understanding of fertility determinism and enhance the value of introducing endocrinological data in fertility studies.     

Genome-wide association studies (GWAS) and post-GWAS analyses for technological traits in Assaf and Churra dairy breeds

This study aimed to perform a GWAS to identify genomic regions associated with milk and cheese-making traits in Assaf and Churra dairy sheep breeds; second, it aimed to identify possible positional and functional candidate genes and their interactions through post-GWAS studies. For 2,020 dairy ewes from 2 breeds (1,039 Spanish Assaf and 981 Churra), milk samples were collected and analyzed to determine 6 milk production and composition traits and 6 traits related to milk coagulation properties and cheese yield. The genetic profiles of the ewes were obtained using a genotyping chip array that included 50,934 SNP markers. For both milk and cheese-making traits, separate single-breed GWAS were performed using GCTA software. The set of positional candidate genes identified via GWAS was subjected to guilt-by-association-based prioritization analysis with ToppGene software. Totals of 84 and 139 chromosome-wise significant associations for the 6 milk traits and the 6 cheese-making traits were identified in this study. No significant SNPs were found in common between the 2 studied breeds, possibly due to their genetic heterogeneity of the phenotypes under study. Additionally, 63 and 176 positional candidate genes were located in the genomic intervals defined as confidence regions in relation to the significant SNPs identified for the analyzed traits for Assaf and Churra breeds. After the functional prioritization analysis, 71 genes were identified as promising positional and functional candidate genes and proposed as targets of future research to identify putative causative variants in relation to the traits under examination. In addition, this multitrait study allowed us to identify variants that have a pleiotropic effect on both milk production and cheese-related traits. The incorporation of variants among the proposed functional and positional candidate genes into genomic selection strategies represent an interesting approach for achieving rapid genetic gains, specifically for those traits difficult to measure, such as cheese-making traits.     

Genome-wide association study using high-density single nucleotide polymorphism arrays and whole-genome sequences for clinical mastitis traits in dairy cattle

Mastitis is a mammary disease that frequently affects dairy cattle. Despite considerable research on the development of effective prevention and treatment strategies, mastitis continues to be a significant issue in bovine veterinary medicine. To identify major genes that affect mastitis in dairy cattle, 6 chromosomal regions on Bos taurus autosome (BTA) 6, 13, 16, 19, and 20 were selected from a genome scan for 9 mastitis phenotypes using imputed high-density single nucleotide polymorphism arrays. Association analyses using sequence-level variants for the 6 targeted regions were carried out to map causal variants using whole-genome sequence data from 3 breeds. The quantitative trait loci (QTL) discovery population comprised 4,992 progeny-tested Holstein bulls, and QTL were confirmed in 4,442 Nordic Red and 1,126 Jersey cattle. The targeted regions were imputed to the sequence level. The highest association signal for clinical mastitis was observed on BTA 6 at 88.97 Mb in Holstein cattle and was confirmed in Nordic Red cattle. The peak association region on BTA 6 contained 2 genes: vitamin D-binding protein precursor (GC) and neuropeptide FF receptor 2 (NPFFR2), which, based on known biological functions, are good candidates for affecting mastitis. However, strong linkage disequilibrium in this region prevented conclusive determination of the causal gene. A different QTL on BTA 6 located at 88.32 Mb in Holstein cattle affected mastitis. In addition, QTL on BTA 13 and 19 were confirmed to segregate in Nordic Red cattle and QTL on BTA 16 and 20 were confirmed in Jersey cattle. Although several candidate genes were identified in these targeted regions, it was not possible to identify a gene or polymorphism as the causal factor for any of these regions.     

Underlying genetic architecture of resistance to mastitis in dairy cattle: A systematic review and gene prioritization analysis of genome-wide association studies

Mastitis, the most frequent disease in dairy cattle. Resistance to mastitis is a complex, polygenic trait controlled by several genes, each with small effects. Genome-wide association studies have been widely used to identify genomic variants associated with complex traits, including resistance to mastitis, to elucidate the underlying genetic architecture of the trait. However, no systematic review and gene prioritization analysis have been conducted to date on GWAS results for resistance to mastitis in dairy cattle. Hence, the objective was to perform a systematic review and gene prioritization analysis of GWAS studies to identify potential functional candidate genes associated with resistance to mastitis-related traits in dairy cattle. Four electronic databases were searched from inception to December 2020, supplemented with multiple sources of gray literature, to identify eligible articles. Annotation for genes and quantitative trait loci (QTL), and QTL enrichment analysis were conducted using GALLO. Gene prioritization analysis was performed by a guilty-by-association approach using GUILDify and ToppGene. From 52 articles included within this systematic review, 30 articles were used for further functional analyses. Gene and QTL annotation resulted in 9,125 and 43,646 unique genes and QTL, respectively, from 39 studies. In general, overlapping of genes across studies was very low (mean ± SD = 0.02% ± 0.07%). Most annotated genes were associated with somatic cell count-related traits and the Holstein breed. Within all annotated genes, 74 genes were shared among Holstein, Jersey, and Ayrshire breeds. Approximately 7.5% of annotated QTL were related to QTL class “health.” Within the health QTL class, 2.6 and 2.2% of QTL were associated with clinical mastitis and somatic cell count-related traits. Enrichment analysis of QTL demonstrated that many enriched QTL were associated with somatic cell score located in Bos taurus autosomes 5, 6, 16, and 20. The prioritization analysis resulted in 427 significant genes after multiple test correction (false discovery rate of 5%) from 26 studies. Most prioritized genes were located in Bos taurus autosomes 19 and 7, and most top-ranked genes were from the cytokine superfamily (e.g., chemokines, interleukins, transforming growth factors, and tumor necrosis factor genes). Although most prioritized genes (397) were associated with somatic cell count-related traits, only 54 genes were associated with clinical mastitis-related traits. Twenty-four genes (ABCC9, ACHE, ADCYAP1, ARC, BCL2L1, CDKN1A, EPO, GABBR2, GDNF, GNRHR, IKBKE, JAG1, KCNJ8, KCNQ1, LIFR, MC3R, MYOZ3, NFKB1, OSMR, PPP3CA, PRLR, SHARPIN, SLC1A3, and TNFRSF25) were reported for both somatic cell count and clinical mastitis-related traits. Prioritized genes were mainly associated with immune response, regulation of secretion, locomotion, cell proliferation, and development. In conclusion, this study provided a fine-mapping of previously identified genomic regions associated with resistance to mastitis and identified key functional candidate genes for resistance to mastitis, which can be used to develop enhanced genomic strategies to combat mastitis by increasing mastitis resistance through genetic selection.     

Fine-mapping of BTA17 using imputed sequences for associations with de novo synthesized fatty acids in bovine milk

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 [–log₁₀(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 PKL4. None of these suggested candidate genes have previously been associated with milk fat synthesis or milk FA composition.     

Quantitative trait loci underlying udder morphology traits in dairy sheep

A genome scan was conducted on the basis of the daughter design to detect quantitative trait loci (QTL) influencing udder morphology traits in Spanish Churra dairy sheep. A total of 739 ewes belonging to 11 half-sib families were genotyped for 182 microsatellite markers covering 3,248.2 cM (Kosambi) of the ovine autosomal genome. Phenotypic traits included scores for 5 linear udder traits: udder depth, udder attachment, teat placement, teat size, and udder shape. Quantitative measurements for the QTL analysis were calculated for each trait from evaluation scores using within-family yield deviations corrected for fixed environmental effects. Joint analysis of all families using Haley-Knott regression identified 5 regions that exceeded the 5% chromosome-wise significance threshold on chromosomes 7, 14, 15, 20, and 26. Based on the across-family results, a within-family analysis was carried out to identify families segregated according to the QTL and to estimate the QTL effect. The allelic substitution effect for individual families ranged from 0.47 to 1.7 phenotypic standard deviation units for udder shape on chromosome 15 and udder depth on chromosome 14, respectively. These QTL regions provide a starting point for further research aimed at the characterization of genetic variability involved in udder traits in Churra sheep. This paper presents the first report of a sheep genome scan for udder-related traits in a dairy sheep outbred population.     

Pathogen-specific effects of quantitative trait loci affecting clinical mastitis and somatic cell count in Danish Holstein cattle

The aim of this study was to investigate whether quantitative trait loci (QTL) affecting the risk of clinical mastitis (CM) and QTL affecting somatic cell score (SCS) exhibit pathogen-specific effects on the incidence of mastitis. Bacteriological data on mastitis pathogens were used to investigate pathogen specificity of QTL affecting treatments of mastitis in first parity (CM1), second parity (CM2), and third parity (CM3), and QTL affecting SCS. The 5 most common mastitis pathogens in the Danish dairy population were analyzed: Streptococcus dysgalactiae, Escherichia coli, coagulase-negative staphylococci, Staphylococcus aureus, and Streptococcus uberis. Data were analyzed using 2 approaches: an independence test and a generalized linear mixed model. Three different data sets were used to investigate the effect of data sampling: all samples, only samples that were followed by antibiotic treatment, and samples from first-crop daughters only. The results showed with high certainty that 2 QTL affecting SCS exhibited pathogen specificity against Staph. aureus and E. coli, respectively. The latter result might be explained by a pleiotropic QTL that also affects CM2 and CM3. Less certain results were found for QTL affecting CM. A QTL affecting CM1 was found to be specific against Strep. dysgalactiae and Staph. aureus, a QTL affecting CM2 was found to be specific against E. coli, and finally a QTL affecting CM3 was found to be specific against Staph. aureus. None of the QTL analyzed was found to be specific against coagulase-negative staphylococci and Strep. uberis. Our results show that particular mastitis QTL are highly likely to exhibit pathogen-specificity. However, the results should be interpreted carefully because the results are sensitive to the sampling method and method of analysis. Field data were used in this study. These kind of data may be heavily biased because there is no standard procedure for collecting milk samples for bacteriological analysis in Denmark. Furthermore, using only the mean SCS from d 10 to 180 after parturition may lead to truncated effects of SCS-QTL when samples collected after d 180 are used. Additionally, repeated samples were used, which could boost the difference in incidence of pathogens between daughters of sires inheriting the positive and negative QTL allele, respectively. However, the magnitude of these effects in this study is unclear.     

Genome-wide association mapping for type and mammary health traits in French dairy goats identifies a pleiotropic region on chromosome 19 in the Saanen breed

Type traits and mammary health traits are important to dairy ruminant breeding because they influence animal health, milking ability, and longevity, as well as the economic sustainability of farms. The availability of the genomic sequence and a single nucleotide polymorphism chip in goats has opened up new fields of investigation to better understand the genes and mechanisms that underlie such complex traits and to be able to select them. Our objective was to perform a genome-wide association study in dairy goats for 11 type traits and somatic cell count (SCC) as proxies for mastitis resistance. A genome-wide association study was implemented using a daughter design composed of 1,941 Alpine and Saanen goats sired by 20 artificial insemination bucks, genotyped with the Illumina GoatSNP50 BeadChip (Illumina Inc., San Diego, CA). This association study was based on both linkage analyses and linkage disequilibrium using QTLmap software (http://dga7.jouy.inra.fr/qtlmap/) interval mapping was performed with the likelihood ratio test using linear regressions. Breeds were analyzed together and separately. The study highlighted 37 chromosome-wide significant quantitative trait loci (QTL) with linkage analyses and 222 genome-wide significant QTL for linkage disequilibrium, for type and SCC traits in dairy goats. Genomic control of those traits was mostly polygenic and breed-specific, suggesting that within-breed selection would be favored for those traits. Of note, Capra hircus autosome (CHI) 19 appeared to be highly enriched in single nucleotide polymorphisms associated with type and SCC, with 2 highly significant regions in the Saanen breed. One region (33–42 Mb) was significantly associated with SCC and includes candidate genes associated with response to intramammary infections (RARA, STAT3, STAT5A, and STAT5B). Another region of the CHI 19 (24.5–27 Mb) exhibited an adverse pleiotropic effect on milk production (milk, fat yield, and protein yield) and udder traits (udder floor position and rear udder attachment) that agreed with the negative genetic correlations that exist between those 2 groups of traits. These QTL were not found in the Alpine breed. In Alpine, the 2 most significant regions were associated with chest depth on CHI 6 (45.8–46.0 Mb) and CHI 8 (80.7–81.1 Mb). These results will be helpful for goat selection in the future and could lead to identification of causal mutations.     

Genome-wide association study for lactation persistency,female fertility,longevity, and lifetime profit index traits in Holstein dairy cattle

Female fertility in Holstein cattle can decline when intense genetic selection is placed on milk production. One approach to improving fertility is to identify the genomic regions and variants affecting fertility traits and then incorporate this knowledge into selection decisions. The objectives of this study were to identify or refine the positions of the genomic regions associated with lactation persistency, female fertility traits (age at first service, cow first service to conception, heifer and cow nonreturn rates), longevity traits (herd life, indirect herd life, and direct herd life), and lifetime profit index in the North American Holstein dairy cattle population. A genome-wide association study was performed for each trait, using a single SNP (single nucleotide polymorphism) regression mixed linear model and imputed high-density panel (777k) genotypes. No associations were identified for fertility traits. Several peak regions were detected for lifetime profit index, lactation persistency, and longevity. The results overlap with previous findings and identify some novel regions for lactation persistency. Previously proposed causative and candidate genes supported by this work include DGAT1, GRINA, and CPSF1, whereas new candidate genes are SLC2A4RG and THRB. Thus, the chromosomal regions identified in this study not only confirm several previous findings but also highlight new regions that may contribute to genetic variation in lactation persistency and longevity-associated traits in dairy cattle.     

Association analysis for young stock survival index with imputed whole-genome sequence variants in Nordic Holstein cattle

Identification of the genetic variants associated with calf survival in dairy cattle will aid in the elimination of harmful mutations from the cattle population and the reduction of calf and young stock mortality rates. We used de-regressed estimated breeding values for the young stock survival (YSS) index as response variables in a genome-wide association study with imputed whole-genome sequence variants. A total of 4,610 bulls with estimated breeding values were genotyped with the Illumina BovineSNP50 (Illumina, San Diego, CA) single nucleotide polymorphism (SNP) genotyping array. Genotypes were imputed to whole-genome sequence variants. After quality control, 15,419,550 SNP on 29 Bos taurus autosomes (BTA) were used for association analysis. A modified mixed-model association analysis was used for a genome scan, followed by a linear mixed-model analysis for selected genetic variants. We identified 498 SNP on BTA5 and BTA18 that were associated with the YSS index in Nordic Holstein. The SNP rs440345507 (Chr5:94721790) on BTA5 was the putative causal mutation affecting YSS. Two haplotype-based models were used to identify haplotypes with the largest detrimental effects on YSS index. For each association signal, 1 haplotype region with harmful effects and the lead associated SNP were identified. Detected haplotypes on BTA5 and BTA18 explained 1.16 and 1.20%, respectively, of genetic variance for the YSS index. We examined whether YSS quantitative trait loci (QTL) on BTA5 and BTA18 were associated with stillbirth. YSS QTL on BTA18 overlapped a QTL region for stillbirth, but most likely 2 different causal variants were responsible for these 2 QTL. Four component traits of the YSS index, defined by sex and age, were analyzed separately by the modified mixed-model approach. The same genomic regions were associated with both bull and heifer calf mortality. Several genes (EPS8, LOC100138951, and KLK family genes) contained a lead associated SNP or were included in haplotypes with large detrimental effects on YSS in Nordic Holstein cattle.     

Genome-wide scan for bovine milk-fat composition. I. Quantitative trait loci for short- and medium-chain fatty acids

A genome-wide scan was performed to identify quantitative trait loci (QTL) for short- and medium-chain fatty acids (expressed in wt/wt %). Milk samples were available from 1,905 cows from 398 commercial herds in the Netherlands, and milk-fat composition was measured by gas chromatography. DNA was available from 7 of the paternal half-sib families: 849 cows and their 7 sires. A genetic map was constructed comprising 1,341 SNP and 2,829 cM, with an average information content of 0.83. Multimarker interval mapping was used in an across-family regression on corrected phenotypes for the 7 half-sib families. Four QTL were found: on Bos taurus autosome (BTA) 6, a QTL was identified for C6:0 and C8:0; on BTA14, a QTL was identified for fat percentage, all odd-chain fatty acids, and C14:0, C16:0, C16:1, and their unsaturation indices; on BTA19, a QTL affected C14:0; and on BTA26, a QTL was identified for the monounsaturated fatty acids and their unsaturation indices. The QTL explained 3 to 19% of phenotypic variance. Furthermore, 49 traits with suggestive evidence for linkage were found on 21 chromosomes. Additional analyses revealed that the QTL on BTA14 was most likely caused by a mutation in DGAT1, whereas the QTL on BTA26 was most likely caused by a mutation in the SCD1 gene. Quantitative trait loci that affect specific fatty acids might increase the understanding of physiological processes regarding fat synthesis and the position of the causal genes.     

Short communication: Uncovering quantitative trait loci associated with resistance to Mycobacterium avium ssp. paratuberculosis infection in Holstein cattle using a high-density single nucleotide polymorphism panel

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of Johne's disease in cattle. Johne's disease is a disease of significant economic, animal welfare, and public health concern around the globe. Therefore, understanding the genetic architecture of resistance to MAP infection has great relevance to advance genetic selection methods to breed more resistant animals. The objectives of this study were to perform a genome-wide association study of previously analyzed 50K genotypes now imputed to a high-density single nucleotide polymorphism panel (777K), aiming to validate previously reported associations and potentially identify additional single nucleotide polymorphisms associated with antibody response to MAP infection. A principal component regression-based genome-wide association study revealed 15 putative quantitative trait loci (QTL) associated with the MAP infection phenotype (serum or milk ELISA tests) on 9 different chromosomes (Bos taurus autosomes 5, 6, 7, 10, 14, 15, 16, 20, and 21). These results validated previous findings and identified new QTL on Bos taurus autosomes 15, 16, 20, and 21. The positional candidate genes NLRP3, IFi47, TRIM41, TNFRSF18, and TNFRSF4 lying within these QTL were identified. Further functional validation of these genes is now warranted to investigate their roles in regulating the immune response and, consequently, cattle resistance to MAP infection.