Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium.

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

Small ruminant lentivirus infections and diseases.

Small ruminant lentiviruses include viruses with diverse genotypes that frequently cross the species barrier between sheep and goats and that display a great genetic variability. These characteristics stress the need to consider the whole host range and to perform local surveillance of the viruses to opt for optimum diagnostic tests, in order to establish control programmes. In the absence of effective vaccines, a comprehensive knowledge of the epidemiology of these infections is of major importance to limit their spread. This article intends to cover these aspects and to summarise information related to characteristics of the viruses, pathogenesis of the infection and description of the various syndromes produced, as well as the diagnostic tools available, the mechanisms involved in transmission of the pathogens and, finally, the control strategies that have been designed until now, with remarks on the drawbacks and the advantages of each one. We conclude that there are many variables influencing the expected cost and benefits of control programs that must be evaluated, in order to put into practice measures that might lead to control of these infections.

Isolation and phylogenetic characterization of Streptococcus halichoeri from a European badger (Meles meles) with pyogranulomatous pleuropneumonia.

Clinical and pathological studies in European badgers (Meles meles) are limited. Badgers play a significant role in the epidemiology of bovine tuberculosis (TB) in some countries and an accurate diagnosis is needed for this infection. However, the lesions of bovine TB are similar to those associated with other pathogens, making pathological diagnosis difficult. In the present study, Streptococcus halichoeri was isolated from a European badger with pyogranulomatous pleuropneumonia and suspected of having tuberculosis. TB and other pathogens able to induce similar lesions were ruled out. Comparative 16S rRNA and rpoB gene sequencing studies showed an identity of 99.51% and 98.28%, respectively, with S. halichoeri. This report represents the third description of this bacterium and the first in an animal species other than the grey seal (Halichoerus grypus). It also shows that S. halichoeri can be associated with a pathological process characterized by granulomatous inflammation and resembling tuberculosis.

Small ruminant lentivirus-induced arthritis: clinicopathologic findings in sheep infected by a highly replicative SRLV B2 genotype.

We describe the clinicopathologic features of an arthritis outbreak in sheep induced by small ruminant lentivirus (SRLV), linked to the presence of a new SRLV isolate phylogenetically assigned to caprine arthritis encephalitis virus-like subgroup B2. Thirteen SRLV seropositive Rasa Aragonesa adult ewes were selected from 5 SRLV highly infected flocks (mean seroprevalence, 90.7%) for presenting uni- or bilateral chronic arthritis in the carpal joint. A complete study was performed, including symptomatology, histopathology, immunocytochemistry, immunohistochemistry, in situ hybridization, and microbiology. The carpus was the joint almost exclusively affected, with 10 sheep (76%) showing a moderate increase in carpal joint size (diameter range, 18-20 cm; normal range, 15-16 cm) without signs of locomotion problems and with 3 ewes (23%) showing severe inflammation with marked increase in diameter (21-24 cm), pain at palpation, and abnormal standing position. Grossly, chronic proliferative arthritis was observed in affected joints characterized by an increased thickness of the synovial capsule and synovial membrane proliferation. Microscopically, synovial membrane inflammation and proliferation and hyperplasia of synoviocytes were observed. More positive cases of SLRV infection were detected by immunocytochemistry of articular fluid than of bronchoalveolar lavage fluid. Immunohistochemistry and in situ hybridization also detected positive cells in the subsynovial connective tissue, lung, mediastinal lymph node, mammary gland, and mammary lymph node. All animals were negative for the presence of Mycoplasma or other bacteria in the articular space. The present outbreak likely represents an adaptation of a caprine virus to sheep. Our results underline the importance of the arthritis induced by SRLV in sheep, a clinical form that might be underestimated.

Nerve compression syndromes of the hand and forearm associated with tumours of non-neural origin and tumour-like lesions.

Nerve compression syndromes caused by non-neural tumours or tumour-like lesions are rare. We retrospectively reviewed 541 consecutive patients operated on by the same surgeon to study nerve compression syndromes in the forearm and hand. There were 414 due to nerve compression and 127 caused by tumours. Twenty-two patients showed compression neuropathy associated with 17 tumours and six tumour-like lesions, with 13 different pathological types. The most common types were fatty and vascular tumours. Twenty-one tumours were extraneural and one was intraneural. The median nerve was affected in nine cases, the ulnar nerve or the dorsal sensory branch of the ulnar nerve in five cases, the posterior interosseous nerve or the superficial radial branch in four cases and the common digital nerves in two cases. There was a concomitant involvement of the median and ulnar nerves in two other patients. Clinically, there were eight different compression neuropathies, of which the most frequent was the carpal tunnel syndrome. The postoperative histology was consistent with preoperative magnetic resonance imaging findings in the vascular and fatty tumours. Pain disappeared completely in 15 out of 16 patients with preoperative pain. All patients had preoperative paraesthesia, which persisted after tumour excision in three patients: attenuated in two patients and unchanged in one. In three patients, we did not observe any change in paresis or amyotrophy. The mean postoperative follow-up was 31 months, without tumour recurrence. The quick Disabilities of the Arm, Shoulder and Hand (DASH) score went from 49.9 points preoperatively to 10.2 points after surgery.

Successful Visna/maedi control in a highly infected ovine dairy flock using serologic segregation and management strategies.

A control system for Visna/maedi virus (VMV) infection based on serologic segregation and management strategies was applied in an infected Spanish dairy Manchega breed sheep flock (n=670) that was affected by a severe respiratory process associated to VMV. The control started in 2004 and consisted on the serological study of animals, segregation in two different flocks (seropositive and seronegative), separate management of flocks, selection of young female lambs for replacement only from seronegative ewes offspring, immediate removal of seropositive animals detected in the seronegative flock and a management tending toward the reduction and final culling of the seropositive flock. The serological control was repeated yearly or twice a year, approximately. Initial VMV seroprevalence of the undivided flock was 66.4% (January 2004) that descended to 47.3%, 12.8%, 2.2% and 0.2% between July 2004 and May 2006. Residual seroprevalence fluctuated slightly thereafter with a peak of 2.2% in April 2008. After segregation, number of animals in the seronegative flock was 378 that descended to 323 in October 2005. Since then, this number has increased steadily reaching 650 sheep in December 2011. The seropositive flock was progressively reduced by culling until its total disappearance in June 2010. This work presents the detailed results obtained in the control strategy against VMV in a single dairy sheep flock by implementing a segregation system based on serologic testing. The system is highly successful, as it reduces to residual levels VMV infection in about two years without the need of culling a high number of animals, as required by other methods. Moreover, the original size flock was been recovered within 8 years and has led to a subjective improvement of animal health and welfare in the flock. The residual seroprevalence could be eliminated at this stage by applying more sensitive molecular or other serological techniques to reach eradication.

ESX-1-induced apoptosis is involved in cell-to-cell spread of Mycobacterium tuberculosis.

Apoptosis modulation is a procedure amply utilized by intracellular pathogens to favour the outcome of the infection. Nevertheless, the role of apoptosis during infection with Mycobacterium tuberculosis, the causative agent of human tuberculosis, is subject of an intense debate and still remains unclear. In this work, we describe that apoptosis induction in host cells is clearly restricted to virulent M. tuberculosis strains, and is associated with the capacity of the mycobacteria to secrete the 6 kDa early secreted antigenic target ESAT-6 bothunder in vitro and in vivo conditions. Remarkably, only apoptosis-inducing strains are able to propagate infection into new cells, suggesting that apoptosis is used by M. tuberculosis as a colonization mechanism. Finally, we demonstrate that in vitro modulation of apoptosis affects mycobacterial cell-to-cell spread capacity, establishing an unambiguous relationship between apoptosis and propagation of M. tuberculosis. Our data further indicate that BCG and MTBVAC vaccines are inefficient in inducing apoptosis and colonizing new cells, correlating with the strong attenuation profile of these strains previously observed in vitro and in vivo.

An insight into a combination of ELISA strategies to diagnose small ruminant lentivirus infections.

A single broadly reactive standard ELISA is commonly applied to control small ruminant lentivirus (SRLV) spread, but type specific ELISA strategies are gaining interest in areas with highly prevalent and heterogeneous SRLV infections. Short (15-residue) synthetic peptides (n=60) were designed in this study using deduced amino acid sequence profiles of SRLV circulating in sheep from North Central Spain and SRLV described previously. The corresponding ELISAs and two standard ELISAs were employed to analyze sera from sheep flocks either controlled or infected with different SRLV genotypes. Two outbreaks, showing SRLV-induced arthritis (genotype B2) and encephalitis (genotype A), were represented among the infected flocks. The ELISA results revealed that none of the assays detected all the infected animals in the global population analyzed, the assay performance varying according to the genetic type of the strain circulating in the area and the test antigen. Five of the six highly reactive (57-62%) single peptide ELISAs were further assessed, revealing that the ELISA based on peptide 98M (type A ENV-SU5, consensus from the neurological outbreak) detected positives in the majority of the type-A specific sera tested (Se: 86%; Sp: 98%) and not in the arthritic type B outbreak. ENV-TM ELISAs based on peptides 126M1 (Se: 82%; Sp: 95%) and 126M2 0,65 0.77 (Se: 68%; Sp: 88%) detected preferentially caprine arthritis encephalitis (CAEV, type B) and visna/maedi (VMV, type A) virus infections respectively, which may help to perform a preliminary CAEV vs. VMV-like typing of the flock. The use of particular peptide ELISAs and standard tests individually or combined may be useful in the different areas under study, to determine disease progression, diagnose/type infection and prevent its spread.

Coxiella burnetii shedding during the peripartum period and subsequent fertility in dairy cattle.

The objective of this study was to assess the effects of Coxiella burnetii shedding or seropositivity on post-partum recovery and subsequent fertility in high-producing dairy cows. Given the difficulty in diagnosing C. burnetii infection at the farm level, an exhaustive series of tests in 43 pregnant animals that delivered at least one live calf were conducted, including blood serology and PCR of milk or colostrum, cotyledons (only at parturition), faeces, vaginal fluid against C. burnetii on gestation Day 171-177, at parturition and on Days 1-7, 8-14, 15-21, 22-28, 29-35 and 90-97 post-partum. During scheduled herd visits, ultrasonography (US) of the genital tract and examination of vaginal fluid were performed on Days 15-21 (V1), 22-28 (V2), 29-35 (V3) and 51-57 (V4) post-partum by the same veterinarian. Logistic regression analysis revealed that the likelihood of suffering endometritis (the presence of echogenic intrauterine fluid (IUF), cervical diameter of ≥4 cm or endometrial thickness ≥0.75 cm) was lower in C. burnetii-seropositive animals (OR = 0.10), compared with C. burnetii-seronegative animals. According to Kaplan-Meier survival analysis, C. burnetii-seronegative and non-shedding cows showed a delayed return to luteal activity and conception was delayed in non-shedding animals, compared with the remaining animals. Overall, the results of our study provide useful insight into the effects of C. burnetii infection on post-partum recovery and subsequent fertility. In particular, animals not infected with Coxiella seem to be susceptible to infection and not protected against the bacterium in dairy herds. The elevated costs of determining an infection at the farm level, make monitoring of cows virtually impossible from a clinical point of view.

Rumen fermentation and histology in light lambs as affected by forage supply and lactation length.

This study determined whether the rumen fermentation and histology traits may reflect the feeding strategy in light lambs (22-24 kg). Thirty-two single Rasa Aragonesa lambs were assigned to one of four treatments in a 2×2 factorial design. The factors were the inclusion of forage in the diet (alfalfa grazing vs. concentrate-fed indoors) and lactation length (weaning at 13 kg vs. suckling until slaughter). A multivariate canonical analysis discriminated individuals among feeding strategies. The main function differentiated weaned concentrate-fed lambs from the rest according to dorsal sac papillae height, ventral sac muscular layer thickness and the proportion of rumen valerate. The second function differentiated suckling concentrate-fed lambs from the rest according to plasma urea levels. Lactation length played an important role on rumen histology and protein utilization, especially in concentrate-fed lambs. Alfalfa grazing light lambs had similar rumen morphometric measures and fermentation characteristics, regardless of milk access.

Novel group A rotavirus G8 P[1] as primary cause of an ovine diarrheic syndrome outbreak in weaned lambs.

Rotavirus is a worldwide major cause of diarrhea outbreaks in neonatal ruminants. An outbreak of ovine diarrheic syndrome (ODS) in 50-75 days-old lambs (weaned lambs) is described. Fecal immunochromatography and intestinal immunohistochemistry for rotavirus group A were performed. In addition, semi-nested multiplex RT-PCR for G and P rotavirus genotyping in combination with sequencing were performed, to support the diagnosis and identify the viral strain. A novel ovine rotavirus group A G8 P[1] strain was determined as the main cause of the ODS observed, whereas other pathogens were ruled out.

Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie.

AIMS: Copper and manganese levels are altered in mice both lacking PrPc and prion-infected brains. The aim of this study was to analyse the effects of manganese and copper imbalance on neuronal apoptosis in a scrapie-infected Tga20 mouse model. METHODS: Immunoreactivities for the apoptotic proteins Bax and active caspase-3 were evaluated in nine regions of the brain of scrapie-infected and control Tga20 mice treated with one of several diets: depleted cooper (-Cu), loaded manganese (+Mn), depleted copper/loaded manganese (-Cu+Mn) and regular diet. Immunohistochemical determination of NeuN was used to detect possible neuronal loss. RESULTS: Intracellular Bax detection was significantly decreased in animals fed with modified diets, particularly in those treated with copper-depleted diets. A decrease in active caspase-3 was primarily observed in animals fed with enhanced manganese diets. Our results show that the -Cu, -Cu+Mn and +Mn diets protected against apoptosis in scrapie-infected mice. However, NeuN immunolabelling quantification revealed that no diet was sufficient to arrest neuronal death. CONCLUSIONS: With regard to apoptosis induction, the response of Tga20 mice to prion infection was similar to that reported for other mice models. Our results demonstrate the neuroprotective effects of -Cu, -Cu+Mn and +Mn diets in a murine model of scrapie. However, neuronal death induced by infection with prions seems to be independent of apoptosis marker signalling. Moreover, copper-modified diets were neuroprotective against the possible toxicity of the prion transgene in Tga20 control and infected mice even though manganese supplementation could not counteract this toxicity.

Visna/maedi virus serology in sheep: survey, risk factors and implementation of a successful control programme in Aragón (Spain).

A serological survey of Visna/maedi virus (VMV) infection involving 274,048 sheep from 554 flocks was undertaken during 2002-2007 in Aragón, North-East Spain. One hundred and two of these flocks enrolled in a VMV control programme to reduce seroprevalence by selecting replacement lambs from seronegative dams and gradual culling of seropositive sheep. Twenty-five flocks were also visited to collect flock management and housing data. All study flocks had seropositive animals and 52.8% of animals tested were seropositive. Among flocks that joined the control programme 66 adopted the proposed measures and reduced seroprevalence significantly by between 26.1% and 76.9% whereas the remaining 36 flocks did not apply the measures and seroprevalence significantly increased. Seroprevalence increased with flock size and the number of days the sheep were housed, and decreased with increasing weaning age and shed open area, suggesting a reduced risk of VMV infection in sheep associated with better ventilation. At the end of the period, 24 flocks were certified as VMV-controlled with a seroprevalence <5%, and seven as VMV-free with 0% seroprevalence. These are the first officially recognised VMV-free flocks in Spain and represent a nucleus of VMV-free replacement animals for other flocks. Moreover, they are evidence of the possibility of eliminating VMV infection without resorting to whole-flock segregation or culling of seropositive sheep.

Effect of scrapie on the stability of housekeeping genes.

Scrapie is the archetype of prion diseases, fatal neurodegenerative disorders that affect humans and animals. Gene expression analysis of normal and infected sheep may provide clues to clarify the molecular mechanisms involved in the neuropathology of these diseases. Real time quantitative PCR has become a powerful and accurate technique for examination of transcription patterns in different biological conditions. One of the critical steps in the comparison of transcription profiles is the selection of stable genes for normalization of expression data. In this work, we have investigated the effect of scrapie on the stability of eight commonly used housekeeping genes in the central nervous system of sheep. We found that their stability decreased in scrapie-infected tissues, with the effect of the disease most evident in the medulla oblongata, a highly affected area of the brain stem. The risk of choosing inappropriate housekeeping genes for expression analysis was evaluated. Although the stability of each reference gene was suitable, a wide variation in expression of target genes (BAX and BCL2) was observed when only one or two housekeeping genes were used to normalize. However, reliable results were obtained with a normalization factor based on three reference genes, regardless of their position in a stability ranking.

The effect of metal imbalances on scrapie neurodegeneration.

Environmental exposure to metal appears to enhance susceptibility to Transmissible Spongiform Encephalopathies (TSEs); however, published data are not conclusive. The current study focuses on assessing the effects of copper depletion and/or manganese enhancement in the diet on susceptibility to Scrapie and this disease progression. The degree of spongiosis was the highest in the animals that received a copper- depleted diet. These observations suggest that this diet contributes to the Scrapie lesions and to the worsening of the condition in animals that have been inoculated with Scrapie. The highest intensities of GFAP immunostaining were also associated with the copper- depleted diet. Dietary supplementation with manganese had a negative effect on neuronal counts. In conclusion, this study demonstrates that certain environmental factors may aggravate neuropathological Scrapie lesions. This is consistent with reports from other neurodegenerative diseases where some metalloenzymes play a pivotal protector role against the oxidative stress associated with pathogenesis.

Effects of housing on the incidence of visna/maedi virus infection in sheep flocks.

The incidence of seroconversion to visna/maedi virus (VMV) infection and its relationship with management and sheep building structure was investigated in 15 dairy sheep flocks in Spain during 3-7years. Incidence rates were 0.09 per sheep-year at risk in semi-intensive Latxa flocks and 0.44 per sheep-year at risk in intensive Assaf flocks and was greatest for the one year old Assaf replacement flock. Separate multivariable models developed for replacement and adult flocks indicated that in both cases seroconversion was strongly associated to direct contact exposure to infected sheep and to being born to a seropositive dam. The latter effect was independent of the mode of rearing preweaning and the risk of seroconversion was similar for sheep fed colostrum and milk from a seropositive or a seronegative dam. These results are further evidence of the efficiency of horizontal VMV transmission by close contact between sheep and also suggest a inheritable component of susceptibility and resistance to infection. In contrast, indirect aerogenous contact with seropositive sheep was not associated with seroconversion as evidenced in replacement sheep housed in separate pens in the same building as adult infected sheep for one year. Consequently, VMV may not be efficiently airborne over short distances and this is important for control of infection. Moreover, there was no relationship between seroconversion and shed open areas. The latter could be related to having examined few flocks in which high infection prevalence dominated the transmission process while ventilation, may depend on a variety of unrecorded factors whose relationship to infection needs to be further investigated.

Immunohistochemical characterisation of classical scrapie neuropathology in sheep.

Neuroinflammation elicited by PrP(res) (resistant prion protein [PrP]) deposits in the central nervous system (CNS) has been shown to involve cellular and oxidative stress responses in bovine spongiform encephalopathy (BSE) as well as in several murine models of transmissible spongiform encephalopathy (TSE). Additionally, deregulation of water homeostasis has been suggested to be a further component of the spongiform changes observed in TSEs. The aim of the present study was to characterize the pathogenic events occurring in the CNS of sheep with spontaneously arising classical scrapie. Brains from seven affected animals and two controls were subject to immunohistochemical and histochemical examinations. Semi-quantitative evaluation of PrP(res) deposits and spongiform changes throughout the encephalon confirmed that PrP(res) deposition elicits significant astroglial and microglial reactions, as evidenced by an increase in the number of glial cells and changes in glial cell morphology involving increased expression of vimentin. The altered expression of metallothionein and heat shock protein 25 (HSP25) suggested that this neuroinflammatory reaction entails cellular and oxidative stress responses. In contrast, there was no change in expression of the membrane-associated water channel aquaporin 1 when PrP(res) accumulated in the brain.

Phylogenetic analysis of SRLV sequences from an arthritic sheep outbreak demonstrates the introduction of CAEV-like viruses among Spanish sheep.

Small ruminant lentiviruses (SRLVs) cause different clinical forms of disease in sheep and goats. So far in Spain, Maedi visna virus-like (MVV-like) sequences have been found in both species, and the arthritic SRLV disease has never been found in sheep until a recent outbreak. Knowing that arthritis is common in goats, it was of interest to determine if the genetic type of the virus involved in the sheep arthritis outbreak was caprine arthritis encephalitis virus-like (CAEV-like) rather than MVV-like. Alignment and phylogenetic analyses on nucleotide and deduced amino acid sequences from SRLV of this outbreak, allowed a B2 genetic subgroup assignment of these SRLV, compatible with a correspondence between the virus genetic type and the disease form. Furthermore, an isolate was obtained from the arthritic outbreak, its full genome was CAEV-like but the pol integrase region was MVV-like. Although its LTR lacked a U3 repeat sequence and had a deletion in the R region, which has been proposed to reduce viral replication rate, its phenotype in sheep skin fibroblast cultures was rapid/high, thus it appeared to have adapted to sheep cells. This outbreak study represents the first report on CAEV-like genetic findings and complete genome analysis among Spanish small ruminants.

PRNP haplotype distribution in Moroccan goats.

Susceptibility/resistance to scrapie in sheep and goats is influenced by host prion protein gene (PRNP) genotype. In this study, we report the analysis of prion protein gene polymorphisms in 137 goats of two Moroccan populations: D'man and Chaouni. We found seven previously described amino acid polymorphisms at codons 37, 127, 137, 142, 154, 222 and 240, as well as three known silent mutations. In addition, we identified three new allelic variants: 101R and 139S in D'man goats and 145D in D'man and Chaouni individuals. The high frequency of the resistant allele 154H could offer genetic protection against the disease to the analysed animals. A total of 12 haplotypes and 28 genotypes were found, the distribution of which shows significant differences between both groups. Moreover, haplotype frequencies were compared with bibliographic data showing that the haplotype distribution of PRNP in Moroccan populations is genetically similar to Southern Italian and Greek goats.