The African Goat Improvement Network: a scientific group empowering smallholder farmers.

The African Goat Improvement Network (AGIN) is a collaborative group of scientists focused on genetic improvement of goats in small holder communities across the African continent. The group emerged from a series of workshops focused on enhancing goat productivity and sustainability. Discussions began in 2011 at the inaugural workshop held in Nairobi, Kenya. The goals of this diverse group were to: improve indigenous goat production in Africa; characterize existing goat populations and to facilitate germplasm preservation where appropriate; and to genomic approaches to better understand adaptation. The long-term goal was to develop cost-effective strategies to apply genomics to improve productivity of small holder farmers without sacrificing adaptation. Genome-wide information on genetic variation enabled genetic diversity studies, facilitated improved germplasm preservation decisions, and provided information necessary to initiate large scale genetic improvement programs. These improvements were partially implemented through a series of community-based breeding programs that engaged and empowered local small farmers, especially women, to promote sustainability of the production system. As with many international collaborative efforts, the AGIN work serves as a platform for human capacity development. This paper chronicles the evolution of the collaborative approach leading to the current AGIN organization and describes how it builds capacity for sustained research and development long after the initial program funds are gone. It is unique in its effectiveness for simultaneous, multi-level capacity building for researchers, students, farmers and communities, and local and regional government officials. The positive impact of AGIN capacity building has been felt by participants from developing, as well as developed country partners.

Using the community-based breeding program (CBBP) model as a collaborative platform to develop the African Goat Improvement Network-Image collection protocol (AGIN-ICP) with mobile technology for data collection and management of livestock phenotypes.

Introduction: The African Goat Improvement Network Image Collection Protocol (AGIN-ICP) is an accessible, easy to use, low-cost procedure to collect phenotypic data via digital images. The AGIN-ICP collects images to extract several phenotype measures including health status indicators (anemia status, age, and weight), body measurements, shapes, and coat color and pattern, from digital images taken with standard digital cameras or mobile devices. This strategy is to quickly survey, record, assess, analyze, and store these data for use in a wide variety of production and sampling conditions. Methods: The work was accomplished as part of the multinational African Goat Improvement Network (AGIN) collaborative and is presented here as a case study in the AGIN collaboration model and working directly with community-based breeding programs (CBBP). It was iteratively developed and tested over 3 years, in 12 countries with over 12,000 images taken. Results and discussion: The AGIN-ICP development is described, and field implementation and the quality of the resulting images for use in image analysis and phenotypic data extraction are iteratively assessed. Digital body measures were validated using the PreciseEdge Image Segmentation Algorithm (PE-ISA) and software showing strong manual to digital body measure Pearson correlation coefficients of height, length, and girth measures (0.931, 0.943, 0.893) respectively. It is critical to note that while none of the very detailed tasks in the AGIN-ICP described here is difficult, every single one of them is even easier to accidentally omit, and the impact of such a mistake could render a sample image, a sampling day's images, or even an entire sampling trip's images difficult or unusable for extracting digital phenotypes. Coupled with tissue sampling and genomic testing, it may be useful in the effort to identify and conserve important animal genetic resources and in CBBP genetic improvement programs by providing reliably measured phenotypes with modest cost. Potential users include farmers, animal husbandry officials, veterinarians, regional government or other public health officials, researchers, and others. Based on these results, a final AGIN-ICP is presented, optimizing the costs, ease, and speed of field implementation of the collection method without compromising the quality of the image data collection.

Low alanine aminotransferase activity gene variant in a Siberian Husky with copper-associated hepatopathy.

BACKGROUND: Alanine aminotransferase (ALT) is commonly used as a marker of hepatocellular injury. Increased serum ALT activity due to hepatocyte injury occurs in copper-associated hepatopathy (CuCH) and other necroinflammatory liver conditions. Blood ALT concentrations are frequently used to monitor therapy in cases of CuCH. Low serum ALT activities have been associated with an allele at a CFA13 locus. CASE PRESENTATION: A 9-year-old female spayed Siberian Husky was diagnosed with CuCH (hepatic copper dry weight 2680 µg/g [normal, 120-400 µg/g; toxic, > 1500 µg/g]) and a normal ALT (78 U/L; reference range, 10-125 U/L). Mild hepatocellular necrosis was evident histologically. Genetic testing (Embark) revealed that the dog was heterozygous for the low ALT activity gene allele. CONCLUSIONS: This case report illustrates the clinical implications for diagnosing and managing necroinflammatory liver disease such as CuCH in dogs with a low ALT activity genotype.

​Comparative genomics of Balto, a famous historic dog, captures lost diversity of 1920s sled dogs.

We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

The impact of using different ancestral reference populations in assessing crossbred population admixture and influence on performance.

Crossbreeding is a process in which animals from different breeds are mated together. The animals produced will exhibit a combination of both additive and non-additive genetic improvement from parental breeds that increase heterozygosity and negate inbreeding depression. However, crossbreeding may also break up the unique and often beneficial gene combinations in parental breeds, possibly reducing performance potential as the benefits of heterosis depends on the type of crossbreeding systems used and heritability of the traits. This effect of crossbreeding, especially on the genome architecture, is still poorly understood with respect to 3-breed crossbreeding systems. Thus, this study examined variation in genomic ancestry estimations relative to pedigree-based estimations and correlated breed composition to key production and health traits. Two rotational crossbred populations, referenced as ProCROSS and Grazecross were assessed and totaled 607 crossbred cattle. ProCROSS is a product of rotational crossbreeding of Viking Red (VKR), Holstein (HOL), and Montbeliarde (MON). In contrast, Grazecross consists of Viking Red (VKR), Normande (NOR), and Jersey (JER). Both breeding programs were aimed at capitalizing on the positive effect of heterosis. The VKR is a marketing term for Swedish Red, Danish Red, and Finnish Ayrshire breed which complicated breed determination. Therefore, genomic breed composition estimates were compared using two different representations of VKR, one of which was based on parents used in the crossing system and a second based on genotypes from the ancestral breeds that comprise VKR. Variation of breed composition estimates were assessed between pedigree and genome-based predictions. Lastly, Genomic estimations were correlated with production and health traits by comparing extreme performance groups to identify the relationship between breed ancestry and performance. With the exception of the JER breed composition in Grazecross, all other estimates of the purebred contribution to the ProCROSS and Grazecross showed a significant difference in their genomic breed estimation when using the VKR ancestral versus the VKR parental reference populations for admixture analysis. These observations were expected given the different relationship of each VKR representation to the crossbred cattle. Further analysis showed that regardless of which VKR reference population was used, the degree of MON and HOL breed composition plays a significant role in milk and fat production in ProCROSS, while the degree of VKR and NOR ancestry were related to improved health performance in Grazecross. In all, identifying the most appropriate and informative animals to use as reference animals in admixture analysis is an important factor when interpreting results of relationship and population structure, but some degree of uncertainty exists when assessing the relationship of breed composition to phenotypic performance.

Genome Wide Association Study with Imputed Whole Genome Sequence Data Identifies a 431 kb Risk Haplotype on CFA18 for Congenital Laryngeal Paralysis in Alaskan Sled Dogs.

Congenital laryngeal paralysis (CLP) is an inherited disorder that affects the ability of the dog to exercise and precludes it from functioning as a working sled dog. Though CLP is known to occur in Alaskan sled dogs (ASDs) since 1986, the genetic mutation underlying the disease has not been reported. Using a genome-wide association study (GWAS), we identified a 708 kb region on CFA 18 harboring 226 SNPs to be significantly associated with CLP. The significant SNPs explained 47.06% of the heritability of CLP. We narrowed the region to 431 kb through autozygosity mapping and found 18 of the 20 cases to be homozygous for the risk haplotype. Whole genome sequencing of two cases and a control ASD, and comparison with the genome of 657 dogs from various breeds, confirmed the homozygous status of the risk haplotype to be unique to the CLP cases. Most of the dogs that were homozygous for the risk allele had blue eyes. Gene annotation and a gene-based association study showed that the risk haplotype encompasses genes implicated in developmental and neurodegenerative disorders. Pathway analysis showed enrichment of glycoproteins and glycosaminoglycans biosynthesis, which play a key role in repairing damaged nerves. In conclusion, our results suggest an important role for the identified candidate region in CLP.

Assessment of Sex, Age, and Metabolism Relationships to Serum Thyroid Concentrations in Retired Alaskan Husky Sled Dogs.

Sled dogs are purpose-bred dogs selected for endurance work. Prior studies in racing dogs showed that serum thyroid parameters (total T4, free T4, and T3) are lower than the reference range in approximately 25% of dogs. Whether this is related to training, breeding, or body condition remains unclear. We hypothesized that retired sled dogs of normal body condition (9-13 years old) would have predominantly normal serum thyroid parameters and that serum thyroid status would be correlated to energy consumption based on metabolic body weight. Eighty-six sled dogs who were deemed healthy on physical exam, not on confounding medications, and without a prior diagnosis of hypothyroidism were included. All dogs' mean body condition scores were 5.1 ± 0.4 and body weight 24.5 ± 4.2 kg at fasting blood collection with stable dietary intake for 3 months before sampling. The total T4, free T4, and T3 serum concentrations were 23.4 ± 9.1 nmol/L, 9.53 ± 4.3 pmol/L, and 0.93 ± 0.39 nmol/L, respectively, with 38% lower than the reference range for total T4, 45% for free T4, and 37% for T3. All dogs were negative for thyroglobulin antibody, and TSH results were within normal ranges. Pearson's correlates based on kilocalories consumed on a metabolic body weight basis for total T4 (R = 0.14), free T4 (R = 0.01) and T3 (R = 0.23) showed poor correlation. No differences were observed between thyroid hormones and age, breed, or sex. Inactive, retired sled dogs can be misdiagnosed with hypothyroidism; therefore, our data suggests that misdiagnosis of hypothyroidism can occur and that the racing Alaskan sled dog has a unique reference range that should be considered when assessing serum thyroid status.

Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids.

Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds.1 Although dogs of variable size are found in the archeological record,2-4 the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations.5 Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFß signaling, and skeletal formation.6-10 Of these, insulin-like growth factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds.8 The identification of a functional mutation associated with IGF1 has thus far proven elusive.6,10,11 Here, to identify and elucidate the role of an ancestral IGF1 allele in the propagation of modern canids, we analyzed 1,431 genome sequences from 13 species, including both ancient and modern canids, thus allowing us to define the evolutionary history of both ancestral and derived alleles at this locus. We identified a single variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the IGF1 gene, creating a duplex. While the derived mutation predominates in both modern gray wolves and large domestic breeds, the ancestral allele, which predisposes to small size, was common in small-sized breeds and smaller wild canids. Our analyses demonstrate that this major regulator of canid body size nearly vanished in Pleistocene wolves, before its recent resurgence resulting from human-imposed selection for small-sized breed dogs.

Development of infrastructure for a systemic multidisciplinary approach to study aging in retired sled dogs.

Canines represent a valuable model for mammalian aging studies as large animals with short lifespans, allowing longitudinal analyses within a reasonable time frame. Moreover, they develop a spectrum of aging-related diseases resembling that of humans, are exposed to similar environments, and have been reasonably well studied in terms of physiology and genetics. To overcome substantial variables that complicate studies of privately-owned household dogs, we have focused on a more uniform population composed of retired Alaskan sled dogs that shared similar lifestyles, including exposure to natural stresses, and are less prone to breed-specific biases than a pure breed population. To reduce variability even further, we have collected a population of 103 retired (8-11 years-old) sled dogs from multiple North American kennels in a specialized research facility named Vaika. Vaika dogs are maintained under standardized conditions with professional veterinary care and participate in a multidisciplinary program to assess the longitudinal dynamics of aging. The established Vaika infrastructure enables periodic gathering of quantitative data reflecting physical, physiological, immunological, neurological, and cognitive decline, as well as monitoring of aging-associated genetic and epigenetic alterations occurring in somatic cells. In addition, we assess the development of age-related diseases such as arthritis and cancer. In-depth data analysis, including artificial intelligence-based approaches, will build a comprehensive, integrated model of canine aging and potentially identify aging biomarkers that will allow use of this model for future testing of antiaging therapies.

Description of breed ancestry and genetic health traits in arctic sled dog breeds.

BACKGROUND: This study describes the presence and frequency of health traits among three populations of dogs traditionally used for sledding and explores their ancestry and breed composition as provided by the commercially available Embark dog DNA test. The three populations include the purebred Siberian Husky and the admixed populations of Alaskan sled dogs and Polar Huskies. While the Siberian Husky represents a well-established breed with extensive historical and health data, the Alaskan sled dog is less studied but has been the subject of nutritional, physiological, and genetic studies related to ancestry and performance. In contrast, the Polar Husky is a relatively obscure and rare group of dogs used for arctic exploration with very little-known information. The three populations were compared using Embark results, providing new insight into the health traits circulating within the populations and the potential ancestral linkage of the health traits between the sledding populations. Embark results are based upon 228,588 single-nucleotide polymorphisms (SNPs) spanning the canine genome, characterized using a custom-designed Illumina beadchip array. RESULTS: Specifically, breed composition was summarized for the two admixed populations with most of the dogs being predominantly categorized as Alaskan husky- type dog or "Supermutt". Mitochondrial and Y chromosome haplogroups and haplotypes were found with Alaskan sled dogs carrying most of the haplogroups and types found in Siberian and Polar Huskies. Genomic principal component analysis reflected population structure corresponding to breed and substructure within the Alaskan sled dogs related to sprint or distance competition. Genetic markers associated with Alanine Aminotransferase activity, Alaskan Husky Encephalopathy, dilated cardiomyopathy, Collie eye anomaly, degenerative myelopathy, ichthyosis, and factor VII deficiency were identified in the populations of sledding breeds. CONCLUSION: These results provide a preliminary description of genetic characteristics found in sledding breeds, improving the understanding and care of working sled dogs.

Direct Phenotyping and Principal Component Analysis of Type Traits Implicate Novel QTL in Bovine Mastitis through Genome-Wide Association.

Our objectives were to robustly characterize a cohort of Holstein cows for udder and teat type traits and perform high-density genome-wide association studies for those traits within the same group of animals, thereby improving the accuracy of the phenotypic measurements and genomic association study. Additionally, we sought to identify a novel udder and teat trait composite risk index to determine loci with potential pleiotropic effects related to mastitis. This approach was aimed at improving the biological understanding of the genetic factors influencing mastitis. Cows (N = 471) were genotyped on the Illumina BovineHD777k beadchip and scored for front and rear teat length, width, end shape, and placement; fore udder attachment; udder cleft; udder depth; rear udder height; and rear udder width. We used principal component analysis to create a single composite measure describing type traits previously linked to high odds of developing mastitis within our cohort of cows. Genome-wide associations were performed, and 28 genomic regions were significantly associated (Bonferroni-corrected p < 0.05). Interrogation of these genomic regions revealed a number of biologically plausible genes whicht may contribute to the development of mastitis and whose functions range from regulating cell proliferation to immune system signaling, including ZNF683, DHX9, CUX1, TNNT1, and SPRY1. Genetic investigation of the risk composite trait implicated a novel locus and candidate genes that have potentially pleiotropic effects related to mastitis.

Graduate Student Literature Review: Understanding the genetic mechanisms underlying mastitis.

Mastitis is the costliest disease facing dairy producers today; consequently, it has been the subject of substantial research focus. Efforts have evolved from an initial focus on understanding the etiology of intramammary infections to the application of preventative measures, including attempts to breed cows that are resistant to infection. However, breeding for resistance to infection has proven difficult, given the complexity of the disease and the high expense associated with assembling high-quality genotypes and phenotypes. This review provides a brief background on mastitis; illustrates current understanding of the genetics influencing mastitis and the application of this knowledge; and discusses challenges and limitations in understanding these mechanisms and applying these findings to genetic improvement strategies.

Time- and population-dependent genetic patterns underlie bovine milk somatic cell count.

The objective of this study was to determine whether genetic regulation of bovine milk somatic cell count (SCC) varied throughout the course of an individual lactation and to identify quantitative trait loci (QTL) that may differentiate populations of chronically mastitic and robustly healthy cows. Milk SCC has long been a proxy for clinical mastitis diagnosis in management and genetic improvement strategies to control the disease. Cows (n = 471) were genotyped on the Illumina BovineHD 777K BeadChip (Illumina Inc., San Diego, CA), and composite milk samples were collected for SCC at 0-1 d in milk (DIM), 3-5 DIM, 10-14 DIM, 90-110 DIM, and 210-230 DIM, with each time span representing key physiological transitions for the cow. Median lactation somatic cell score (SCS) and area under the SCS curve were calculated from farm test data. A total of 8 genome-wide associations were performed and 167 SNP spanning the genome were significantly associated (false discovery rate <0.05). Of these associated regions, 27 of 48 associated QTL were novel for clinical mastitis or SCC. The linkage disequilibrium block surrounding the associated QTL or a 1-Mb window in the absence of linkage disequilibrium was interrogated for candidate genes, and many of those identified were related to multiple arms of the immune system, including toll-like receptor signaling, macrophage activation, B-cell maturation, T-cell recruitment, and the complement pathway. These genes included EXOC4, BAMBI, ITSN2, IL34, FCN3, CD8A, and CD8B. In addition, we identified populations of robustly healthy (SCS ≤4 from 10-14 DIM until study end), chronically mastitic (SCS >4 from 10-14 DIM until study end), and average cows with fluctuating SCS, and calculated fixation indices to identify regions of the genome differentiating these 3 populations. A total of 12 SNP were identified that showed moderate allelic differentiation (Wright's F statistic, FST ≥ 0.4) between the "chronic," "healthy," and "average" populations of cows. Candidate genes in the region surrounding differentiated QTL were related to cell signaling and immune response, such as JAKMIP1 and MADCAM1. The wide range of significantly associated QTL spanning the genome and the diversity of gene functions reinforces that mastitis is a complex trait and suggests that selection based on lactation stage-specific SCS rather than a generalized score may lead to greater success in breeding mastitis-resistant cows.

A Stop-Gain Mutation within MLPH Is Responsible for the Lilac Dilution Observed in Jacob Sheep.

A coat color dilution, called lilac, was observed within the Jacob sheep breed. This dilution results in sheep appearing gray, where black would normally occur. Pedigree analysis suggested an autosomal recessive inheritance. Whole-genome sequencing of a dilute case, a known carrier, and sixteen non-dilute sheep was used to identify the molecular variant responsible for the coat color change. Through investigation of the genes MLPH, MYO5A, and RAB27A, we discovered a nonsynonymous mutation within MLPH, which appeared to match the reported autosomal recessive nature of the lilac dilution. This mutation (NC_019458.2:g.3451931C>A) results in a premature stop codon being introduced early in the protein (NP_001139743.1:p.Glu14*), likely losing its function. Validation testing of additional lilac Jacob sheep and known carriers, unrelated to the original case, showed a complete concordance between the mutation and the dilution. This stop-gain mutation is likely the causative mutation for dilution within Jacob sheep.

A Genetic Investigation of Island Jersey Cattle, the Foundation of the Jersey Breed: Comparing Population Structure and Selection to Guernsey, Holstein, and United States Jersey Cattle.

For two centuries, Jersey cattle were exported globally, adapting to varying climates and production systems, yet the founding population remained genetically isolated on the Island of Jersey. The Island of Jersey formally allowed the importation of pure Jersey cattle in 2008. This study characterized the genetic variation of 49 popular bulls from the Island of Jersey born from 1964 to 2004 and compared them to 47 non-Island Jersey bulls and cows, primarily from the United States In addition, 21 Guernsey cattle derived from the Island of Guernsey and 71 Holstein cattle served as reference populations for genetic comparison. Cattle were genotyped on the Illumina BovineHD Beadchip producing 777,962 SNPs spanning the genome. Principal component analysis revealed population stratification within breed reflective of individual animal's continental origin. When compared to Holstein and Guernsey, all Jersey clustered together by breed. The Jersey breed demonstrated increased inbreeding in comparison to Holstein or Guernsey with slightly higher estimates of inbreeding coefficients and identity-by-descent. The Island and United States Jersey have relatively similar, yet statistically different inbreeding estimates despite vastly different population sizes and gene flow. Signatures of selection within Island Jersey were identified using genome-wide homozygosity association and marker-based FST that provided population informative single-nucleotide polymorphism (SNPs). Biological significance of the homozygosity association results identified multiple genes on chromosomes 5, 24, and 27, involved in immune function and cellular processes. Overall, genomic variation was identified between the Island and non-Island Jersey cattle producing population informative SNPs and differing runs of homozygosity (ROH) over immune regulation and metabolic genes. Results on inbreeding measures and ROH may reflect varying effective population size or differential selection with grazing systems promoting natural selection for traits such as parasite resistance, whereas confinement systems demonstrate a more intensive artificial selection. More broadly, differences in breed formation, particularly between the two Channel Island breeds, likely contributed to the variation in ROH and inbreeding. This research provides a reference for the Jersey breed based on the genetic foundation of the Island cattle as compared to the intensively selected United States cattle, and identifies regions of the genome for future investigation of immune regulation and metabolic processes.

Longitudinal Phenotypes Improve Genotype Association for Hyperketonemia in Dairy Cattle.

The objective of our study was to identify genomic regions associated with varying concentrations of non-esterified fatty acid (NEFA), ß-hydroxybutyrate (BHB), and the development of hyperketonemia (HYK) in longitudinally sampled Holstein dairy cows. Our study population consisted of 147 multiparous cows intensively characterized by serial NEFA and BHB concentrations. To identify individuals with contrasting combinations in longitudinal BHB and NEFA concentrations, phenotypes were established using incremental area under the curve (AUC) and categorized as follows: Group (1) high NEFA and high BHB, group (2) low NEFA and high BHB), group (3) low NEFA and low BHB, and group (4) high NEFA and low BHB. Cows were genotyped on the Illumina Bovine High-density (777K) beadchip. Genome-wide association studies using mixed linear models with the least-related animals were performed to establish a genetic association with HYK, BHB-AUC, NEFA-AUC, and the comparisons of the 4 AUC phenotypic groups using Golden Helix software. Nine single-nucleotide polymorphisms were associated with high longitudinal concentrations of BHB and further investigated. Five candidate genes related to energy metabolism and homeostasis were identified. These results provide biological insight and help identify susceptible animals thus improving genetic selection criteria thereby decreasing the incidence of HYK.

Genomic Approaches Identify Novel Gene Associations with Out of Season Lambing in Sheep.

Sheep are seasonally polyestrous, traditionally breeding when the day length shortens in the autumn. The changing photoperiod stimulates reproductive hormones through a series of chemical pathways, ultimately leading to cyclicity. Some breeds of sheep, such as the Polypay and Dorset, have been selected for reduced seasonality and can lamb year-round. Despite this selection, there is still variation within these breeds in the ability to lamb out of season. The identification of out of season lambing quantitative trait loci has the potential to improve genetic progress using genomic selection schemes. Association studies, fixation index (FST), and runs of homozygosity (ROH) were evaluated to identify regions of the genome that influence the ability of ewes to lamb out of season. All analyses used genotypic data from the Illumina Ovine HD beadchip. Genome-wide associations were tested both across breeds in 257 ewes and within the Dorset and Polypay breeds. FST was measured across breeds and between UK and US Dorsets to assess population differences. ROH were estimated in ewes to identify homozygous regions contributing to out of season lambing. Significant associations after multiple testing correction were found through these approaches, leading to the identification of several candidate genes for further study. Genes involved with eye development, reproductive hormones, and neuronal changes were identified as the most promising for influencing the ewe's ability to lamb year-round. These candidate genes could be advantageous for selection for improved year-round lamb production and provide better insight into the complex regulation of seasonal reproduction.

Udder and teat conformational risk factors for elevated somatic cell count and clinical mastitis in New York Holsteins.

Our primary objective was to identify udder and teat conformational risk factors associated with the occurrence of elevated somatic cell count (SCC) and clinical mastitis using a prospective cohort study design with careful assessment of exposure and disease outcomes. Mastitis prevalence was evaluated by parity across 6 sampling periods representing key physiological transitions during lactation: 0-1 day in milk (DIM), 3-5 DIM, 10-14 DIM, 50-60 DIM, 90-110 DIM, and 210-230 DIM. Cows were scored for front and rear teat length, width, end shape, and placement, fore udder attachment, udder cleft, udder depth, rear udder height, and rear udder width. Two independent multivariable logistic regression models were used to generate odds ratios (OR) for elevated SCC (≥ 200,000 cells/ml) and farm-diagnosed clinical mastitis. We identified that loose fore udder attachment (reference level: strong fore udder attachment, OR = 2.1, 95% confidence interval (CI) = 1.2-3.8) and flat teat end shape (reference level: round teat end shape, OR = 1.4, 95% CI = 1.1-1.9) increased the odds of an elevated SCC event, whereas a negative California Mastitis Test score at 0-1 DIM decreased the odds of an elevated SCC event (OR = 0.6, 95% CI = 0.4 to 0.8). Loose fore udder attachment (reference level: strong fore udder attachment, OR = 3.7, 95% CI = 1.3-10.7), flat teat end shape (reference level: round teat end shape, OR = 1.5, 95% CI = 1.0-2.4), low rear udder height (reference level: intermediate rear udder height, OR = 2.8, 95% CI = 0.3-6.2), and increasing rear teat width (OR = 2.2, 95% CI = 1.2-4.4) heightened the odds of developing clinical mastitis. We identified that within our study cohort, loose fore udder attachment and flat teat ends had an important association with increased odds of both an elevated SCC event and clinical mastitis diagnosis. The identification of these udder and teat conformational risk factors for mastitis can provide farmers an effective and inexpensive tool to manage mastitis.

A longitudinal study of digital cushion thickness and its function as a predictor for compromised locomotion and hoof lesions in Holstein cows.

Lameness is a major animal welfare and economic issue for the dairy industry and is a challenge to overcome due to multifaceted causes. Digital cushion thickness (DCT) is a strong predictor of lameness and is phenotypically associated with incidence of claw horn disruption lesions (CHDL; sole ulcers and white line disease). We hypothesized that DCT varies between digits and across lactation within the cow. This variation could be characterized to predict the occurrence of CHDL or compromised locomotion. BCS, visual locomotion score (VLS), DCT, and presence or absence of lesions were collected at 4 time points: <40 d prepartum (DPP), 1 to 30 d in milk (DIM), 90 to 120 DIM, and ≥255 DIM for 183 commercial Holstein cows enrolled in the study. Cows underwent digital sonographic examination for the measurement of DCT evaluated at the typical sole ulcer site beneath the flexor tuberosity for the right front medial and lateral digits and right hind medial and lateral digits. Factors such as parity number and stage in lactation were obtained from farm management software (DairyComp 305; Valley Agricultural Software, Tulare, CA). Cows were grouped by parity: primiparous (parity = 1) or multiparous (parity ≥ 2). The prevalence of CHDL among time points ranged from 0% to 4.2% for primiparous cows vs. 2.5% to 25% for multiparous cows, whereas the prevalence of lameness based on VLS of 3 to 5 ranged from 1.7% to 8.3% for primiparous cows vs. 12.7% to 33% for multiparous cows. DCT varied within primiparous and multiparous cows based on stage of lactation and digit (P < 0.05) and was thicker for both parity groups prior to dry off (≥255 DIM) and thinnest prior to calving (<40 DPP) and after peak lactation (90 to 120 DIM). The DCT of the front medial digit was thickest for primiparous heifers, whereas the hind lateral digit was thickest for multiparous cows. The DCT of the hind medial digit was thinnest for both parity groups. Parity group and DCT of the hind lateral digit <40 DPP were important predictors of CHDL (P < 0.05), whereas parity group and DCT of the hind lateral digit and front lateral digit at 1 to 30 DIM were key predictors of VLS lameness (P < 0.05). These results may help identify animals with higher odds of developing these diseases by highlighting key time points and specific digits of importance for monitoring. In addition, it improves our biological understanding of the relationship between DCT and lameness.

Mutation responsible for congenital photosensitivity and hyperbilirubinemia in Southdown sheep.

OBJECTIVE To identify the genetic cause for congenital photosensitivity and hyperbilirubinemia (CPH) in Southdown sheep. ANIMALS 73 Southdown sheep from a CPH research flock and 48 sheep of various breeds from commercial flocks without CPH. PROCEDURES Whole-genome sequencing was performed for a phenotypically normal Southdown sheep heterozygous for CPH. Heterozygous variants within Slco1b3 coding exons were identified, and exons that contained candidate mutations were amplified by PCR assay methods for Sanger sequencing. Blood samples from the other 72 Southdown sheep of the CPH research flock were used to determine plasma direct and indirect bilirubin concentrations. Southdown sheep with a plasma total bilirubin concentration < 0.3 mg/dL were classified as controls, and those with a total bilirubin concentration ≥ 0.3 mg/dL and signs of photosensitivity were classified as mutants. Sanger sequencing was used to determine the Slco1b3 genotype for all sheep. Genotypes were compared between mutants and controls of the CPH research flock and among all sheep. Protein homology was measured across 8 species to detect evolutionary conservation of Slco1b. RESULTS A nonsynonymous mutation at ovine Chr3:193,691,195, which generated a glycine-to-arginine amino acid change within the predicted Slco1b3 protein, was significantly associated with hyperbilirubinemia and predicted to be deleterious. That amino acid was conserved across 7 other mammalian species. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested a nonsynonymous mutation in Slco1b3 causes CPH in Southdown sheep. This disease appears to be similar to Rotor syndrome in humans. Sheep with CPH might be useful animals for Rotor syndrome research.