Genetics of resistance to mastitis in dairy cattle

Genetic variability of mastitis resistance is well established in dairy cattle. Many studies focused on polygenic variation of the trait, by estimating heritabilities and genetic correlation among phenotypic traits related to mastitis such as somatic cell counts and clinical cases. The role of Major Histocompatibility Complex in the susceptibility or resistance to intrammamary infection is also well documented. Finally, development from molecular genome mapping led to accumulating information of quantitative trait loci (QTL) related to mastitis resistance and better understanding of the genetic determinism of the trait. From economic and genetic analyses, and according to welfare and food safety considerations and to breeders and consumer's concern, there is more and more evidence that mastitis should be included in breeding objective of dairy cattle breeds. Many countries have implemented selection for mastitis resistance based on linear decrease of somatic cell counts. Given biological questioning, potential unfavourable consequences for very low cell counts cows are regularly investigated. Improvement of selection accuracy for mastitis resistance is ongoing and includes: advances in modelling, optimal combination of mastitis related traits and associated predictors, such as udder morphology, definition of global breeding objective including production and functional traits, and inclusion of molecular information that is now available from QTL experiments.     

Genetic parameters for energy balance, fat /protein ratio, body condition score and disease traits in German Holstein cows

Various health problems in dairy cows have been related to the magnitude and duration of the energy deficit post partum. Energy balance indicator traits like fat/protein ratio in milk and body condition score could be used in selection programmes to help predicting breeding values for health traits, but currently there is a lack of appropriate genetic parameters. Therefore, genetic correlations among energy balance, fat/protein ratio, and body condition score, and mastitis, claw and leg diseases, and metabolic disorders were estimated using linear and threshold models on data from 1693 primiparous cows recorded within the first 180 days in milk. Average daily energy balance, milk fat/protein ratio and body condition score were 8 MJ NEL, 1.13 and 2.94, respectively. Disease frequencies (% cows with at least one case) were 24.6% for mastitis, 9.7% for metabolic disorders and 28.2% for claw and leg diseases. Heritability estimates were 0.06, 0.30 and 0.34 for energy balance, fat/protein ratio and body condition score, respectively. For the disease traits, heritabilities ranged between 0.04 and 0.15. The genetic correlations were, in general, associated with large standard errors, but, although not significant, the results suggest that an improvement of overall health can be expected if energy balance traits are included into future breeding programmes. A low fat/protein ratio might serve as an indicator for metabolic stability and health of claw and legs. Between body condition and mastitis, a significant negative correlation of -0.40 was estimated. The study provides a new insight into the role energy balance traits can play as auxiliary traits for robustness of dairy cows. It was concluded that both, fat/protein ratio and body condition score, are potential variables to describe how well cows can adapt to the challenge of early lactation. However, the genetic parameters should be re-estimated on a more comprehensive data set.     

Mammary expression of new genes to combat mastitis

Continual advances in the ability to produce transgenic animals make it likely that such animals will become important components of animal agriculture. The full benefit of the technology, and justification of its initial cost outlay, will be dependent on the establishment within these animals of new traits not easily achievable by other means. Potential applications include enhanced nutrient digestibility with reduced fecal losses, significantly altered milk composition with superior nutritional properties, and enhanced disease resistance. Our goal is to enhance mastitis resistance of dairy cows by enabling the cells of the mammary gland to secrete additional antibacterial proteins. Proof of concept has been obtained through experimentation with a transgenic mouse model. Three lines of mice were developed that produce varying levels of lysostaphin in their milk. This protein has potent anti-staphylococcal activity and its secretion into milk confers substantial resistance to infection caused by intramammary challenge with Staphylococcus aureus, a major mastitis pathogen. Additional antibacterial proteins are being sought that will complement lysostaphin. A potential benefit of transgenic application of antibacterial proteins is the concomitant sparing in the agricultural use of antibiotics currently used as human therapeutics. Antibacterial proteins, such as lysostaphin, are not typically used as injectable or oral therapeutics because of immune-mediated or digestive destruction of their activity. In contrast, the immune system of transgenic animals will not consider the transgenic protein as being foreign. In addition we are exploring the potential of involution or mastitis responsive promoter elements for use in subsequent transgenic experiments designed to restrict lysostaphin production to these important time points. It is anticipated that genomics will play a role in unveiling candidate genes whose promoter elements will enable desired temporal expression patterns. The transgenic approach to insertion of new genetic material into agriculturally important animals is feasible but requires extensive prior evaluation of the transgene and transgene product in model systems.     

Comparison of variance components for test-day electrical conductivity of milk and test-day somatic cell score for first lactation cows in an experimental herd

In recent decades, electrical conductivity (EC) has been introduced as an indicator of mastitis, and genetic selection based on this trait may be possible. In this study, genetic parameters for test-day EC and test-day somatic cell score (SCS) were compared. Data were collected from a Danish experimental herd, including daily records of EC and SCS from 265 first lactation cows. Different genetic models were tested, and a random regression animal model with a 4th order Legendre polynomial for the permanent environmental effect for both traits, a 1st order Legendre polynomial for the additive genetic effect of EC and a 2nd order Legendre polynomial for the additive genetic effect of SCS, gave the best fit. The patterns of the curves were similar for both permanent environmental and additive genetic variance for the two traits. Heritability estimates ranged from 0.05 to 0.12, and from 0.01 to 0.09, for EC and SCS, respectively. The estimate of genetic correlation between the traits was high, and ranged from 0.86 to 0.98. Based on these results, EC could be a potential indicator trait in a breeding programme where selection for increased mastitis resistance is included.     

奶牛乳房炎防治的研究进展

奶牛乳房炎作为奶牛较为常见且影响较大的一种疾病,给畜牧业与食品业带来了严重的经济损失。传统的抗生素治疗方法因其在临床上容易出现广谱耐药和药物残留等问题受到广泛争议。所以,探索新型的治疗方案迫在眉睫。以中草药制剂、疫苗等为代表的生物制剂因具有较多的优点而被人们广泛关注。本文作者基于前人的研究成果,阐述了奶牛乳房炎的新型治疗方法,为进一步研究奶牛乳房炎的治疗提供一定的参考与帮助。     

New Strategies to Prevent Mastitis

Bovine mastitis remains as the disease causing the biggest economic losses to the dairy industry, despite the intensive research and prevention measures at herd level carried out for decades. Antibiotics are widely used to combat mastitis, but focus should be shifted from treatment to more economical and efficient prevention. The bacteriological aetiology of mastitis has changed from contagious to environmental pathogens, which has reduced the efficacy of the traditional mastitis control strategies. Considerable progress in the understanding of epidemiology, immunology, diagnostics and pathogenesis of mastitis has been made. The modern molecular biological methods offer good possibilities for the research of the epidemiological and virulence aspects of bacteria, which may help in building‐up specific mastitis control strategies for dairy herds. Studies on the host response and relationship between somatic cell count and susceptibility to mastitis offer tools for genetic improvement of dairy cows. Biotechnological approaches for mastitis prevention are in the developmental stage, but many problems are associated, e.g. with vaccination of dairy cows against mastitis. Different methods of immunomodulation for the prevention of mastitis have shown promise in experimental trials, but the evidence is not yet enough to support commercial applications. Improving nutrition, housing and environment of dairy cattle are still crucial in the prevention of mastitis, especially during the most susceptible period after parturition. New milking techniques including robotic milking may provide better possibility for proper milking and improved udder health. Mastitis control should be part of the herd health programme in the dairy herds. In this paper, results from recent research and proposals for new prevention strategies in the field of mastitis are reviewed.     

奶牛乳房炎主要病原菌感染流行规律研究进展

乳房炎作为全球性奶牛养殖业的重要疾病,因对社会经济、养殖行业和人类健康的巨大影响使人们从发病机理、疾病诊断、预防等方面对其进行了不断的研究与探讨。作者立足于前期尤其是近几年的研究文献,以引起奶牛乳房炎的重要原因——病原菌为中心展开,探讨其感染类型、奶牛与病原菌及病原菌相互之间的关系。奶牛乳房炎是由包括病原菌的侵袭及宿主奶牛自身抵抗力等多种因素共同作用导致,乳腺对病原菌的入侵应答能力,病原与病原之间或促进或抑制都对其发生产生影响。金黄色葡萄球菌是公认的奶牛乳房炎的主要传染性病原菌,其独特的生物学特性使得其在体内难以治疗,并且耐药性普遍存在;无乳链球菌是环境性还是传染性病原尚有争议,在中国感染率较高,对大部分抗生素仍旧敏感,相对于其他病原菌治愈率较高,畜群清除容易;大肠埃希氏菌被作为环境性病原体,乳房炎感染的分离率仍较高,抗生素治疗结果还有待商榷,耐药性普遍存在并增强;牛支原体近十年的感染率有所上升,在国内外都是严重的乳房炎致病因素,治疗效果不佳,且耐药性正在增强,疫苗开发困难。文章对上述几种主要病原菌的流行、危害与防治等研究进行综述,以期为奶牛生产管理和科学研究方面提供参考。     

Effects of diseases on reproductive performance in Swedish Red and White dairy cattle

The objectives of this study were to evaluate the effect of diseases on days open (DO), days to first breeding (DFB) and days from first breeding to conception (DFBC) using survival analysis models, and to assess the significance of the sire component and its possible confounding effect. The data consisted of a random sample of 20% of all herds enrolled in Swedish recording system and using 100% artificial insemination with at least 15 Swedish Red and White cows calving in 1991. The follow-up period was from 45 to 145 d after calving. After editing, the data sets had 23,927, 28,197, and 22,089 cows for days open, days to first breeding, and days from first breeding to conception, respectively. The Cox models included parity, calving season, cow milk production and age at first calving as fixed effects, and herd and sire as random effects. Ten disease groups were considered as possible risk factors for the reproductive traits. Disease groups were treated differently if they occurred before or after 45 d postpartum. Diseases occurring in the first 45 d after calving were treated as time-independent covariates and diseases occurring after day 45 were treated as time-dependent covariates for days open and days to first breeding. The percentages of censored cows were 35% for days open, 19% for days to first breeding, and 33% for days from first breeding to conception. Days open increased in cows with dystocia, stillbirth, retained placenta, metritis, or other diseases occurring in the first 45 d after calving, and in cows with metritis, mastitis, or other diseases occurring after 45 d. Days to first breeding increased in cows with stillbirth, retained placenta, milk fever, mastitis, foot and leg problems, or other diseases occurring before day 45, and in cows with metritis, mastitis, foot and leg problems, or other diseases occurring after 45 d. Days to first breeding decreased in cows treated for ovulatory dysfunctions either before or after 45 d. Days from first breeding to conception increased in cows with dystocia, stillbirth, retained placenta, metritis, or ovulatory dysfunctions occurring before first breeding, and in cows with mastitis occurring after first breeding. Although the additive genetic components were significant for all traits considered, the sires did not act as confounders because only a small amount of variability for the traits considered in this study was explained by the sires, with estimated heritabilities of 2% on the logarithmic scale and from 3 to 4% on the real scale.     

Genetic analysis of protein yield,udder health,and female fertility in first-parity Danish Holstein cows

Abstract

Genetic parameters for protein yield, clinical mastitis, SCS, number of inseminations (NI), and days from first to last insemination (FLI) were estimated for first-parity Danish Holstein cows. The objective was to estimate genetic correlations between the five traits mentioned above and to study whether NI and FLI are measures of the same trait. Records containing information on approximately 200 000 cows were analysed using tri-variate animal models. The genetic correlations between the udder health traits and the fertility traits were favourable and in the range from 0.17 to 0.42, whereas the genetic correlations between protein yield and the fertility traits were unfavourable and ranged from 0.43 to 0.52. These results highlight the importance of continuing to emphasize functional traits in future breeding programmes. The genetic correlation between the fertility traits was 0.82. Based on this result, it cannot be concluded that NI and FLI are measures of the same trait.     

Genetic factors affecting susceptibility of dairy cows to udder pathogens

Bovine mastitis remains the most costly disease in dairy cattle. Breeding for resistance to udder pathogens has been proposed as a complementary tool to therapeutic and prophylactic measures not totally effective against the disease. This paper reviews factors affecting cows' susceptibility to pathogens at the animal, cellular/hormonal and DNA levels. Such factors will be useful in achieving genetic improvement for resistance only if they have desirable properties at the genetic and immunological levels. Because such properties are not always of significant magnitude, further research is necessary to identify characteristics of resistance in cows, considering the constant and complex interactions that occur between hosts and pathogens.     

The genetic contribution of cows to the prevalence of mastitis in the following generation

Investigations of mastitis prevalence were performed in 1227 dam-daughter pairs during 1985-1988. From the records of the last 10 years, the findings concerning mammary gland were obtained. Six herds of agricultural co-operatives in the Brno region were investigated. In the early period the Bohemian Pied breed, later the crosses of this breed with Red Holstein and a low genetic proportion of Ayrshire cattle, dominated in the set of cows. Udder health was assessed using the clinical and bacteriological findings in individual udder quarters and the results of the rapid mastitis test NK. Based on this data, the cows were divided into two groups--resistant and susceptible. The lactation order in which the disease appeared for the first time was of great importance. The occurrence of the disease in daughters and udder health in dams were in a significant relation (P less than or equal to 0.01). While nearly 50% of daughters of susceptible dams were affected, it was only 25% in daughters of the resistant group. The assessment of heritability of resistance to mastitis was carried out on the principle of dam-daughter regression. The index of heritability ?2 = 0.52 +/- 0.06 was calculated. The results show that the genetic contribution of dams to the susceptibility of daughters to mastitis is significant.     

Genetic associations of in-line recorded milkability traits and udder conformation with udder health

Milkability and udder conformation traits of Swedish Holstein (SH) and Swedish Red (SR) cows from 93 herds with automatic milking systems or conventional milking parlors were used to study genetic relationships to lactation average somatic cell score (LSCS) and incidence of clinical mastitis (CM). Estimated genetic correlations between measures of milking speed (average flow rate, milking time and box time) and LSCS ranged between 0.29 and 0.57 and showed that high milking speed is associated with increasing LSCS. Regressions indicated a curvilinear relationship. Genetic correlations between milking speed and CM showed similar values as for LSCS in SH cows, but were inconsistent in SR cows. Shallow udder and strong fore udder attachment were consistently correlated with good udder health. The unfavorable relationships between milking speed and udder health traits should be considered together with a few udder conformation traits when selecting for better milkability.     

荷斯坦母牛TLR10基因PCR-SSCP分析

设计15对引物,采用PCR-SSCP技术检测Toll样受体10（Toll-like receptor 10,TLR10）基因在210头荷斯坦母牛中的多态性,分析该基因对荷斯坦母牛乳房炎抗性的影响。结果显示,TLR10基因在检测的荷斯坦母牛中都不存在多态性,该基因区域可能不存在影响乳房炎抗性的遗传标记。     

Mycoplasmal mastitis in dairy herds.

Mycoplasmal bovine mastitis is potentially a highly contagious disease that can cause severe economic problems in affected herds. The purchase of replacement heifers and cows are frequently the origin of mycoplasmal mastitis outbreaks in previously Mycoplasma-free herds. Purchased cows and heifers should be quarantined and tested for mycoplasmal mastitis before admission to the regular herd. Detection of Mycoplasma-infected cows by culture of milk is straightforward, although there are problems of sensitivity for its detection in milk samples that are inherent to the nature of the disease and laboratory procedures. After detection of infected cows, the best way to protect the herd is to culture all cows in the herd, cows with clinical mastitis, and all heifers and cows after calving and before entering the milking herd. Control of mycoplasmal mastitis requires test and culling from the herd of Mycoplasma-positive cows if possible. When a large number of cows are infected, strict segregation with adequate management is an option; however, animals in this group should never re-enter the Mycoplama-free herd. The functioning of the milking equipment and milking procedures should be evaluated carefully and any flaws corrected. There is no treatment for mycoplasmal mastitis, and vaccination has not proven to be efficacious to prevent, decrease the incidence, or ameliorate the clinical signs of mycoplasmal mastitis. Waste milk should not be fed to calves without pasteurization. M bovis may cause several other pathologies in animals of different ages on a farm, including pneumonia, arthritis, and ear infections. The survival of mycoplasmas in different farm microenvironments needs to be further investigated for its impact on the epidemiology of the disease.     

Genome-wide scan for selective sweeps identifies novel loci associated with resistance to mastitis in German Holstein cattle

Domestication and selection significantly changed phenotypic and behavioural traits in modern domestic animals. In this study, to identify the genomic regions associated with mastitis, genomic data of German Holstein dairy cattle were analysed. The samples were genotyped using the Bovine 50 K SNP chip. For each defined healthy and sick group, 133 samples from 13,276 genotyped dairy cows were selected based on mastitis random residual effects. Grouping was done to infer selection signatures based on XP-EHH statistic. The results revealed that for the top 0.01 percentile of the obtained XP-EHH values, five genomic regions on chromosomes 8, 11, 12, 14 and 26 of the control group, and four regions on chromosomes 3, 4 (two regions) and 22 of the case group, have been under selection. Also, consideration of the top 0.1 percentile of the XP-EHH values, clarified 21 and 15 selective sweeps in the control and case group, respectively. This study identified some genomic regions containing potential candidate genes associated with resistance and susceptibility to mastitis, immune system and inflammation, milk traits, udder morphology and different types of cancers. In addition, these regions overlap with some quantitative trait loci linked to clinical mastitis, immunoglobulin levels, somatic cell score, udder traits, milk fat and protein, milk yield, milking speed and veterinary treatments. It is noteworthy that we found two regions in the healthy group (on chromosomes 12 and 14) with strong signals, which were not described previously. It is likely that future research could link these identified genomic regions to mastitis. The results of the current study contribute to the identification of causal mutations, genomic regions and genes affecting mastitis incidence in dairy cows.     

Mastitis in dairy cows in large-scale farming operations from the genetic aspect

Genetic predisposition to mastitis was studied in 893 dairy cows of the Black Pied Lowland breed, daughters of 19 breeding bulls used in stocks with large-scale production technology and with loose housing, over the years 1980 to 1983. Every cow with positive bacteriological diagnosis or with a clinical manifestation of the disease was considered as suffering from mastitis. High resistance to mastitis was determined in the progeny of AO-4, EM-01, NC-17, NB-10, NEB-15, NUN-3, Nx-33 bulls, while opposite results were recorded in the progeny of NAR-45, NAR-47, NER-01, NOM-19 and REN-100 bulls. Higher milk efficiency, by 9 to 408 litres of milk was observed in positive dairy cows in the years of study. The coefficient of heritability (h2) is 0.3032. It can be concluded that the systematic control of cows from the aspect of suitability for large-scale production technology and resistance to mastitis, and evaluation of bulls according to predisposition of their daughters to this disease, is very favourable in view of the prophylaxy of bovine mastitis.     

免疫大师公牛女儿的疾病抗性分析

为探究通过抗病选育的免疫大师公牛女儿的疾病抗性情况,试验收集上海地区3个同时使用免疫大师公牛和普通公牛冻精牧场的5 112条个体疾病记录,采用Logistic回归法分析了犊牛出生季节、成母牛年龄、父亲类型（免疫大师和普通公牛）对部分常见奶牛疾病发病风险的影响。结果表明,出生季节和年龄分别对犊牛和成母牛各类疾病的发病风险有显著影响（P<0.05）;父亲类型对乳房炎的发病风险在部分群体中有显著影响（P<0.05）。与普通公牛的女儿相比,免疫大师公牛女儿乳房炎发病风险更低。综合本研究结果,免疫大师公牛的抗病能力选育技术有效,其在中国奶牛群体的后代表现出更好的疾病抗性,尤其是提高了奶牛乳房炎抗性,为利用育种手段提高奶牛群体的抗病能力和养殖效益提供了可行的技术路线。     

牛主要抗病候选基因的研究进展

牛抗病基因与其自身的抗病性和免疫能力有一定的相关性,因此研究相关抗病基因对提高牛自身免疫能力和选育优良后代有重要意义,文章着重介绍了国内外关于天然抗性相关巨噬细胞蛋白1（natual resistant macrophage protein 1,Nramp1）、主要组织相容性复合物（major histocompatibility complex,MHC）、甘露糖结合凝集素（maflnan binding lectin,MBL）、Toll样受体（Toll-like receptors,TLR）及干扰素基因（interferon,IFN）与牛某些疾病相关性的研究进展,及其是否可用于后代育种的分子标记,如MHC与奶牛的乳房炎密切相关;牛TLR4基因的外显子1760 C>T突变中的CC基因型可作为奶牛乳房炎抗性筛选中的分子标记等。笔者认为研究这些抗病基因可更深层次了解牛的抗病机制,同时借助先进的技术手段如分子标记、基因工程等,可更好的选育出抗病后代,抗病基因在育种中的应用将是未来研究抗病性和免疫能力的主要方向。     

奶牛乳房炎诊断和治疗方法的研究进展

奶牛乳房炎是奶牛养殖业中的重要疾病,可降低产奶量和乳品质,增加治疗和预防成本,给牧场带来经济损失。病因多样,包括细菌、病毒和支原体等病原体均可引起传染性乳房炎。临床症状复杂,需要特定实验室方法进行准确诊断。奶牛乳房炎传统方法诊断准确性低,分子生物学检测发展前景大,基于微生物培养试剂盒和环介导等技术有望提高奶牛乳房炎诊断准确性和治疗精准度。治疗方面,抗生素类药物是常用的方法,但容易引起细菌耐药性和药物残留问题,需要开发新型药物用于奶牛乳房炎治疗。近年的研究显示,噬菌体有望作为替代品治疗奶牛乳房炎,部分植物及其衍生物具有抗菌作用,天然分泌因子如乳铁蛋白和磷脂酶A2也具有治疗潜力,但仍需深入研究。     

荷斯坦母牛TLR10基因PCR-SSCP分析

设计15对引物,采用PCR-SSCP技术检测Toll样受体10(Toll-like receptor 10,TLR10)基因在210头荷斯坦母牛中的多态性,分析该基因对荷斯坦母牛乳房炎抗性的影响。结果显示,TLR10基因在检测的荷斯坦母牛中都不存在多态性,该基因区域可能不存在影响乳房炎抗性的遗传标记。