Evidence for linkage between the caprine leucocyte antigen (CLA) system and susceptibility to CAE virus-induced arthritis in goats

The distribution of caprine leucocyte antigens (CLA) in goats from four different breeds (n=546) affected by caprine arthritis-encephalitis virus (CAEV)-induced arthritis were determined and compared breed for breed with those of infected but clinically healthy controls (n=402). Differences in frequencies of some of the CLA specificities between the affected and control groups were found, but after correction of the ordinary P values for number of observed alleles, only the CLA Be7 specificity in the Saanen breed showed a significant deviation at the 0.05 probability level. Animals of the Saanen breed carrying this specificity are less prone to develop arthritis after CAE virus infection than goats lacking this specificity. Eleven groups (multiple-case families or halfsibling groups with at least two informative diseased offspring/group) were analyzed for manifestation of the disease and segregation of the parental haplotypes. The results of the maximum likelihood test of association (P<0.005) and the calculated high lod score value of 5.70 give evidence for linkage between the locus encoding the determined class I CLA alleles and a hypothetical locus (i) coding for genes responsible for arthritis resistance/susceptibility. The particular class I CLA allele associated with the disease susceptibility varied from family to family, however. These data provide the first evidence that CAE virus-induced arthritis in the goat is genetically influenced by the MHC system; they also suggest that susceptibility/resistance genes are not directly associated with the determined class I gene products but rather are in close genetic linkage.     

Sheep major histocompatibility (OLA) complex: linkage between a scrapie susceptibility/resistance locus and the OLA complex in Ile-de-France sheep progenies

As seen on their family trees, Ile-de-France sheep with scrapie show genetic susceptibility to this disease, which is transmitted via scr ^s, an autosomal recessive gene. Scrapie occurred in homozygous recessive sheep, whereas the presence of the dominant resistance allele Scr ^r sufficed to prevent this disease in heterozygous animals. This hypothesis, previously proposed by Parry (1962), was tested in a study involving 133 crossings of sheep of different genotypes, and verified in the observed progenies. In a contaminated environment, susceptibility to the disease seemed to be transmitted by the scr ^s gene, whose frequency was increasing and varied in different progenies: the gene was propagated by inbreeding combined with selection; scrapie did not appear in the progeny of a homozygous resistant ram with the Scr ^r/Scr^r genotype. On the family trees, linkage between the Scr locus and the OLA-A and -B loci is clearly visible; it often allowed the transmission of resistance or susceptibility haplotypes to be detected by OLA typing and followed from one generation to the next. The Scr ^r, OLA-A4, B6 haplotype was not found in any diseased sheep born before 1979, but was propagated by healthy sheep. During and after 1979, several recombinations of this haplotype were observed, giving a recombined haplotype with reciprocal linkage (scr ^s, OLA-A4, B6), disseminated by one sire in particular. The rate of recombination of Scr and OLA loci is estimated to be between 11 and 16 %. The possibility of early selection against the disease without loss of qualities desired by the breeder is discussed.     

Interaction between the nematophagous fungus Duddingtonia flagrans and infective larvae of Haemonchus contortus (Nematoda: Trichostrongyloidea)

The interaction between Duddingtonia flagrans and infective larvae of Haemonchus contortus was studied in vitro under optical and scanning electron microscopy. Trap formation by the fungus started 9 hours after inoculation and first larvae were found 11 hours after larval inoculation on colonies grown on the surface of dialysis membranes. Scanning electron micrographs were taken 12, 24, 36 and 48 h after larval predation. Details of predation structures and fungus-larvae interaction are described. A mucilaginous substance occurred at the points of adherence of traps to nematode cuticle. Bacteria were also found at some points of interaction between fungus and larval cuticle. Cuticle penetration by fungus hyphae occurred only 48 h after predation.     

No association between genetic ancestry and susceptibility to asthma or atopy in Canary Islanders

Asthma is a complex respiratory disease characterized by chronic inflammation of airways and frequently associated with atopic symptoms. The population from the Canary Islands, which has resulted from a recent admixture of North African and Iberian populations, shows the highest prevalence of asthma and atopic symptoms among the Spanish populations. Although environmental particularities would account for the majority of such disparity, genetic ancestry might play a role in increasing the susceptibility of asthma or atopy, as have been demonstrated in other recently African-admixed populations. Here, we aimed to explore whether genetic ancestry was associated with asthma or related traits in the Canary Islanders. For that, a total of 734 DNA samples from unrelated individuals of the GOA study, self-reporting at least two generations of ancestors from the Canary Islands (391 asthmatics and 343 controls), were successfully genotyped for 83 ancestry informative markers (AIMs), which allowed to precisely distinguishing between North African and Iberian ancestries. No association was found between genetic ancestry and asthma or related traits after adjusting by demographic variables differing among compared groups. Similarly, none of the individual AIMs was associated with asthma when results were considered in the context of the multiple comparisons performed (0.005?≤?p value?≤?0.042; 0.221?≤?q value?≤?0.443). Our results suggest that if genetic ancestry were involved in the susceptibility to asthma or related traits among Canary Islanders, its effects would be modest. Larger studies, examining more genetic variants, would be needed to explore such possibility.     

A search for associations between major histocompatibility complex restriction fragment length polymorphism bands and resistance to Haemonchus contortus infection in sheep

Polymorphic bands were detected within the DQB and DRB regions of the ovine major histocompatibility complex by probing TaqI digested DNA from three large sheep half-sib families derived from a highly resistant ram. All animals were phenotypically assessed for Haemonchus contortus resistance by faecal egg counts and associations with RFLP bands and haplotypes were estimated using mixed model, best linear unbiased prediction statistical methods. Although the highly resistant sire was homozygous at the MHC, no significant associations were found between any band or haplotype and faecal egg count.     

Trends and challenges in the effective and sustainable control of Haemonchus contortus infection in sheep. Review

Haemonchosis, with its very wide distribution, has become a very important production constraint in sheep farms in tropical, subtropical and temperate regions worldwide. Various intrinsic and extrinsic factors determine the survival of Haemonchus contortus and hence the development of the disease in the animal. In general, control of gastrointestinal nematode infestation in sheep relies heavily on anthelmintic treatments. However, the indiscriminate use of these drugs has led to the widespread emergence of drug resistant strains of parasites, that has necessitated the development and use of various parasite control methods such as grazing management, biological agents and vaccines and the selection of resistant breeds of animals, with or without moderate use of anthelmintics. The ultimate goal of such control programs is to enhance productivity, while minimising risks regarding drug resistance and consumer and environmental concerns. This review attempts to highlight the different methods employed in the control of haemonchosis in sheep and the practical limitations associated with both control programs and the internal and external factors associated with the parasite and its microenvironment.     

No association of Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in susceptibility to gallbladder cancer

Gallbladder carcinoma (GBC) is a leading cause of cancer deaths in north India. Evidence has highlighted the role of abnormal DNA methylation patterns on inappropriate gene expression in development and progression of various cancers. 5,10-Methylenetetrahydrofolate reductase (MTHFR) plays a major role in provision of methyl groups for DNA methylation. A C/T substitution in MTHFR at nucleotide 677 results in replacement of ala222-to-val in the N-terminal catalytic domain of protein, and causes considerable decrease in enzymatic activity. Thus, MTHFR C677T polymorphism may influence genetic susceptibility to GBC. The present study aimed to examine the role of C677T MTHFR polymorphism in conferring genetic susceptibility to GBC. The present study included 146 proven GBC patients and 210 healthy controls. Genotyping was done by PCR-RFLP method. The MTHFR C677T genotypes in control population were in Hardy-Weinberg equilibrium (p = ns). No statistically significant difference was observed in frequency of variant TT genotype in GBC patients in comparison to healthy controls (4.1% and 2.9%). Stratification of GBC patients on the basis of presence or absence of gallstones showed no significant association with the disease. Further, gender and age of onset of the disease did not show any significant association. In conclusion, the present study indicates that the genetic risk for GBC is not modulated by MTHFR C677T polymorphism.     

Haemonchus contortus (Nematoda: Trichostrongylidae) is much more sensitive than Caenorhabditis elegans (Nematoda: Rhabditidae) to the ovicidal action of thiabendazole

When eggs of the trichostrongylid nematode Haemonchus contortus were exposed to thiabendazole, the concentration required to prevent hatching in 90% of the eggs (MIC90) was found to be 0.1 microg/ml (using 1% dimethylsulfoxide [DMSO] as solvent). In contrast, eggs of the free-living rhabditid nematode Caenorhabditis elegans hatched at normal rates at a concentration 200 times higher, i.e., 20 microg/ml, and showed only a partial inhibitory effect at a concentration 1,200 times higher, i.e., 120 microg/ml (in 3% DMSO). Because solubility limitations precluded the testing of higher concentrations of thiabendazole, a more soluble derivative, 5-([1-methylethoxy]carbonylamino)-2-(4-thiazloyl)1H-++ +benzimidazolyliminoacetic acid N,N-diethylethanamine salt, was tested against C. elegans eggs. The MIC90 was found to be 400 microg/ml, and although the derivative was not tested against H. contortus eggs, this finding further suggests that C. elegans eggs have an exceptionally low degree of benzimidazole sensitivity.     

Immunity to Haemonchus contortus and the cellular response to helminth antigens in the mammary gland of non-lactating sheep.

Cellular exudates induced by infusion with helminth antigens were examined in non-lactating mammary glands of ewes immune to infection with the abomasal nematode, Haemonchus contortus. Secondary immunological responsiveness was expressed in two ways. Firstly, antigens from adult H. contortus elicited larger eosinophil-rich cellular exudates in immune compared to non-immune ewes. In this situation, secondary responsiveness in the mammary gland must have been generated through abomasal infection with the parasite. Secondly, repeated infusion with the antigens from adult H. contortus increased the size of cellular exudates in both immune and non-immune ewes. Eosinophils predominated but numbers of macrophages and lymphocytes were also increased. In this second situation, secondary responsiveness must have been either supplemented in immune ewes or derived completely in non-immune ewes by contact with helminth antigens through the mammary gland. The helminth antigens which induce eosinophil exudates in the mammary gland may not be potently protective against H. contortus. Furthermore, eosinophil exudation may not be an in vivo correlate of immunity which is directly useful for discriminating protective antigens and applicable to vaccine development. Infusion with antigens from adult forms of either H. contortus or Trichostrongylus colubriformis elicited cellular exudates equally well in immune ewes primed by infusion with H. contortus adult antigens 7 days beforehand. In addition, antigens from infective larvae of H. contortus elicited cellular exudates more potently than antigens from adult worms. However, vaccination with irradiated larvae has shown that species-specific protective immunity for H. contortus is stronger than cross-protective immunity conferred by T. colubriformis.(ABSTRACT TRUNCATED AT 250 WORDS)     

No consistent association between changes in genetic diversity and adaptive responses of Australian acacias in novel ranges

Common garden studies comparing trait differences of exotic species between native and introduced ranges rarely incorporate an analysis of genetic variation, but simply infer that trait shifts between ranges are genetically determined. We compared four growth-related traits (total biomass, relative growth rate RGR, specific leaf area SLA, and root to shoot ratio R:S) of five invasive Fabaceae species (Acacia cyclops, A. longifolia, A. melanoxylon, A. saligna, Paraserianthes lophantha), grown in a common garden experiment using seeds from introduced and native ranges across Australia. Chloroplast microsatellite loci were used to compare genetic diversity of native and introduced populations to determine standing genetic diversity and infer introduction history. We asked whether shifts in traits associated with faster growth due to enemy release in the introduced range were associated with levels of genetic diversity associated with introduction history. We found differences in traits between ranges, although these traits varied among the species. Compared to native-range populations, introduced-range Acacia longifolia had greater biomass and larger SLA; A. cyclops had greater RGR; and A. melanoxylon displayed lower R:S. Genetic diversity in the introduced range was lower for one of those species, A. longifolia, and two others that did not show differences in traits, A. saligna and P. lophantha. Diversity was higher in the introduced range for A. melanoxylon and did not differ among ranges for A. cyclops. These patterns of genetic diversity suggest that a genetic bottleneck may have occurred following the introduction of A. longifolia, A. saligna and P. lophantha. In contrast greater or comparable genetic diversity in the introduced range for A. melanoxylon and A. cyclops suggests introductions from multiple sources. This study has shown that a reduction in genetic diversity in the introduced range is not necessarily associated with a reduced capacity for adaptive responses or invasion potential in the novel range.     

Differential stability of the benzimidazole (BZ)-tubulin complex in BZ-resistant and BZ-susceptible isolates of Haemonchus contortus and Trichostrongylus colubriformis.

The binding of [3H]mebendazole ([3H]MBZ) to tubulin from BZ-susceptible (BZ-S) and BZ-resistant (BZ-R) isolates of Haemonchus contortus and Trichostrongylus colubriformis was investigated using charcoal extraction and gel filtration techniques. The amount of [3H]MBZ bound at infinite free ligand concentration (Bmax) was significantly reduced for the BZ-R isolate compared with the BZ-S isolate in both species when assayed by charcoal extraction. However, Bmax was increased to comparable levels for both BZ-S and BZ-R isolates of each species when assayed by the less stringent gel filtration technique. These results indicate that the BZ-tubulin interaction in trichostrongylid nematodes is comprised of a minimum of two components. As similar levels of total [3H]MBZ binding were observed for both BZ-S and BZ-R isolates of each species when assayed by gel filtration, it is suggested that the reduction in the pseudo-irreversible BZ binding component in BZ-R isolates results in an increase in the level of reversible BZ binding and therefore provides a survival advantage to BZ-R nematodes.     

Proteomic analysis of the abomasal mucosal response following infection by the nematode, Haemonchus contortus, in genetically resistant and susceptible sheep

Sheep have a variable ability to resist gastrointestinal nematode infection, but the key factors mediating this response are poorly defined. Here we report the first large-scale application of quantitative proteomic technologies to define proteins that are differentially abundant between sheep selectively bred to have an enhanced (resistant) or reduced (susceptible) ability to eliminate nematodes. Samples were collected from the abomasal mucosa three days after experimental challenge with the nematode, Haemonchus contortus. This timing reflects the initial interaction of host and parasite, and the tissue represents the immediate interface. We identified and quantified more than 4400 unique proteins, of which 158 proteins showed >1.5 fold difference between the resistant and susceptible sheep. Trefoil factor 2, a member of RAS oncogene family (RAP1A) and ring finger protein 126 were amongst the proteins found to be highly abundant in the abomasal surface of resistant sheep, whereas adenosine deaminase and the gastrokine-3 like precursor were found at higher levels in susceptible sheep. Construction of gut proteome interaction networks identified mitochondrial function and energetic partitioning as important components of an effective nematode eliminating response. The differentially abundant proteins may be useful targets for phenotypic tests that aim to identify sheep with an enhanced ability to resist nematode infection.