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Although susceptibility to scrapie is largely controlled by the PRNP gene, we have searched for additional genomic regions that affect scrapie incubation time in sheep, using two half-sib families with a susceptible PRNP genotype and naturally infected by scrapie. Quantitative trait loci were detected on OAR6 and OAR18.

To determine the relationships among closely related populations or species, two methods are commonly used in the literature: phylogenetic reconstruction or multivariate analysis. The aim of this article is to assess the reliability of multivariate analysis. We describe a method that is based on principal component analysis and Mantel correlations, using a two-step process: The first step consists of a single-marker analysis and the second step tests if each marker reveals the same typology concerning population differentiation. We conclude that if single markers are not congruent, the compromise structure is not meaningful. Our model is not based on any particular mutation process and it can be applied to most of the commonly used genetic markers. This method is also useful to determine the contribution of each marker to the typology of populations. We test whether our method is efficient with two real data sets based on microsatellite markers. Our analysis suggests that for closely related populations, it is not always possible to accept the hypothesis that an increase in the number of markers will increase the reliability of the typology analysis.

Research has been conducted on Iberian cattle origin. The authors have investigated the genetic data combined with the geographical positioning via the use of geostatistical models, and have characterized Portugues, Spanish and French cattle breeds for their genetic diversity.

Misfolding of the cellular PrP (PrP c ) protein causes prion disease, leading to neurodegenerative disorders in numerous mammalian species, including goats. A lack of PrP c induces complete resistance to prion disease. The aim of this work was to engineer Alpine goats carrying knockout (KO) alleles of PRNP, the PrP c -encoding gene, using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the PRNP Ter mutation previously described in Norwegian goats. Genome editors were injected under the zona pellucida prior to the electroporation of 565 Alpine goat embryos/oocytes. A total of 122 two-cell-stage embryos were transferred to 46 hormonally synchronized recipient goats. Six of the goats remained pregnant and naturally gave birth to 10 offspring. Among the 10 newborns, eight founder animals carrying PRNP genome-edited alleles were obtained. Eight different mutated alleles were observed, including five inducing KO mutations. Three founders carried only genome-edited alleles and were phenotypically indistinguishable from their wild-type counterparts. Among them, one male carrying a one base pair insertion leading to a KO allele is currently used to rapidly extend a PRNP-KO line of Alpine goats for future characterization. In addition to KO alleles, a PRNP del6 genetic variant has been identified in one-third of founder animals. This new variant will be tested for its potential properties with respect to prion disease. Future studies will also evaluate the effects of genetic background on other characters associated with PRNP KO, as previously described in the Norwegian breed or other species., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

The recent emergence of chronic wasting disease (CWD) in Europe has become a new public health risk for monitoring of wild and farmed cervids. This disease, due to prions, has proliferated in North America in a contagious manner. In several mammalian species, polymorphisms in the prion protein gene (PRNP) play a crucial role in the susceptibility to prions and their spread. To obtain a reliable picture of the distribution of PRNP polymorphisms in the two most common cervid species in France, we sequenced the open reading frame (ORF) of this gene in 2114 animals, 1116 roe deer (Capreolus capreolus) and 998 red deer (Cervus elaphus). Selection criteria such as historical origin, spatial distribution and sex ratio have been integrated to establish this sample collection. Except for one heterozygous animal with a non-synonymous mutation at codon 37 (G37A), all the 1116 French roe deer were monomorphic. Red deer showed greater variation with two non-synonymous substitutions (T98A; Q226E), three synonymous substitutions (codons 21, 78 and 136) and a new 24pb deletion (Δ 69-77 ). We found significant regional variations between French regions in the frequency of the identified substitutions. After cloning of the PRNP ORF from animals presenting multiple non-synonymous polymorphisms, we identified six haplotypes and obtained a total of twelve genotypes. As in other European countries, we highlighted the apparent homogeneity of PRNP in the French roe deer and the existence of a greater diversity in the red deer. These results were in line with European phylogeographic studies on these two species., (© 2024. The Author(s).)

The structure of cellular prion proteins encoded by the prion protein gene (PRNP) impacts susceptibility to transmissible spongiform encephalopathies, including chronic wasting disease (CWD) in deer. The recent emergence of CWD in Northern European reindeer (Rangifer tarandus), moose (Alces alces alces) and red deer (Cervus elaphus), in parallel with the outbreak in North America, gives reason to investigate PRNP variation in European deer, to implement risk assessments and adjust CWD management for deer populations under threat. We here report PRNP-sequence data from 911 samples of German red, roe (Capreolus capreolus), sika (Cervus nippon) and fallow deer (Dama dama) as well as additional data from 26 Danish red deer close to the German border and four zoo species not native to Germany. No PRNP sequence variation was observed in roe and fallow deer, as previously described for populations across Europe. In contrast, a broad PRNP variation was detected in red deer, with non-synonymous polymorphisms at codons 98, 226 and 247 as well as synonymous mutations at codons 21, 78, 136 and 185. Moreover, a novel 24 bp deletion within the octapeptide repeat was detected. In summary, 14 genotypes were seen in red deer with significant differences in their geographical distribution and frequencies, including geographical clustering of certain genotypes, suggesting "PRNP-linages" in this species. Based on data from North American CWD and the genotyping results of the European CWD cases, we would predict that large proportions of wild cervids in Europe might be susceptible to CWD once introduced to naive populations., (© 2024. The Author(s).)

The feral cattle of the subantarctic island of Amsterdam provide an outstanding case study of a large mammalian population that was established by a handful of founders and thrived within a few generations in a seemingly inhospitable environment. Here, we investigated the genetic history and composition of this population using genotyping and sequencing data. Our inference showed an intense but brief founding bottleneck around the late 19th century and revealed contributions from European taurine and Indian Ocean Zebu in the founder ancestry. Comparative analysis of whole-genome sequences further revealed a moderate reduction in genetic diversity despite high levels of inbreeding. The brief and intense bottleneck was associated with high levels of drift, a flattening of the site frequency spectrum and a slight relaxation of purifying selection on mildly deleterious variants. Unlike some populations that have experienced prolonged reductions in effective population size, we did not observe any significant purging of highly deleterious variants. Interestingly, the population's success in the harsh environment can be attributed to preadaptation from their European taurine ancestry, suggesting no strong bioclimatic challenge, and also contradicting evidence for insular dwarfism. Genome scan for footprints of selection uncovered a majority of candidate genes related to nervous system function, likely reflecting rapid feralization driven by behavioral changes and complex social restructuring. The Amsterdam Island cattle offers valuable insights into rapid population establishment, feralization, and genetic adaptation in challenging environments. It also sheds light on the unique genetic legacies of feral populations, raising ethical questions according to conservation efforts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The Shadoo and PrP prion protein family members are thought to be functionally related, but previous knockdown/knockout experiments in early mouse embryogenesis have provided seemingly contradictory results. In particular, Shadoo was found to be indispensable in the absence of PrP in knockdown analyses, but a double-knockout of the two had little phenotypic impact. We investigated this apparent discrepancy by comparing transcriptomes of WT, Prnp 0/0 and Prnp 0/0 Sprn 0/0 E6.5 mouse embryos following inoculation by Sprn- or Prnp-ShRNA lentiviral vectors. Our results suggest the possibility of genetic adaptation in Prnp 0/0 Sprn 0/0 mice, thus providing a potential explanation for their previously observed resilience., (© 2022. The Author(s).)

Despite their central economic and cultural role, the origin of cattle populations living in Indian Ocean islands still remains poorly documented. Here, we unravel the demographic and adaptive histories of the extant Zebus from the Mayotte and Madagascar islands using high-density SNP genotyping data. We found that these populations are very closely related and both display a predominant indicine ancestry. They diverged in the 16th century at the arrival of European people who transformed the trade network in the area. Their common ancestral cattle population originates from an admixture between an admixed African zebu population and an Indian zebu that occurred around the 12th century at the time of the earliest contacts between human African populations of the Swahili corridor and Austronesian people from Southeast Asia in Comoros and Madagascar. A steep increase in the estimated population sizes from the beginning of the 16th to the 17th century coincides with the expansion of the cattle trade. By carrying out genome scans for recent selection in the two cattle populations from Mayotte and Madagascar, we identified sets of candidate genes involved in biological functions (cancer, skin structure, and UV-protection, nervous system and behavior, organ development, metabolism, and immune response) broadly representative of the physiological adaptation to tropical conditions. Overall, the origin of the cattle populations from Western Indian Ocean islands mirrors the complex history of human migrations and trade in this area., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

To date, chronic wasting disease (CWD) is the most infectious form of prion disease affecting several captive, free ranging and wild cervid species. Responsible for marked population declines in North America, its geographical spread is now becoming a major concern in Europe. Polymorphisms in the prion protein gene (PRNP) are an important factor influencing the susceptibility to prions and their rate of propagation. All reported cervid PRNP genotypes are affected by CWD. However, in each species, some polymorphisms are associated with lower attack rates and slower progression of the disease. This has potential consequences in terms of genetic selection, CWD diffusion and strain evolution. CWD also presents a zoonotic risk due to prions capacity to cross species barriers. This review summarizes our current understanding of CWD control, focusing on PRNP genetic, strain diversity and capacity to infect other animal species, including humans., (© 2021. The Author(s).)

Shadoo belongs to the prion protein family, an evolutionary conserved and extensively studied family due to the implication of PrP in Transmissible Spongiform Encephalopathies. However, the biological function of these genes remains poorly understood. While Sprn-knockdown experiments suggested an involvement of Shadoo during mouse embryonic development, Sprn-knockout experiments in 129Pas/C57BL/6J or 129Pas/FVB/NCr mice did not confirm it. In the present study, we analyzed the impact of Sprn gene invalidation in a pure FVB/NJ genetic background, using a zinc finger nuclease approach. The in-depth analysis of the derived knockout transgenic mice revealed a significant increase in embryonic lethality at early post-implantation stages, a growth retardation of young Sprn-knockout pups fed by wild type mice and a lactation defect of Sprn-knockout females. Histological and transcriptional analyses of knockout E7.5 embryos, E14.5 placentas and G7.5 mammary glands revealed specific roles of the Shadoo protein in mouse early embryogenesis, tissue development and differentiation with a potential antagonist action between PrP and Shadoo. This study thus highlights the entanglement between the proteins of the prion family.

As the largest European herbivore, the wisent (Bison bonasus) is emblematic of the continent wildlife but has unclear origins. Here, we infer its demographic and adaptive histories from two individual whole-genome sequences via a detailed comparative analysis with bovine genomes. We estimate that the wisent and bovine species diverged from 1.7 × 10 6 to 850,000 years before present (YBP) through a speciation process involving an extended period of limited gene flow. Our data further support the occurrence of more recent secondary contacts, posterior to the Bos taurus and Bos indicus divergence (∼150,000 YBP), between the wisent and (European) taurine cattle lineages. Although the wisent and bovine population sizes experienced a similar sharp decline since the Last Glacial Maximum, we find that the wisent demography remained more fluctuating during the Pleistocene. This is in agreement with a scenario in which wisents responded to successive glaciations by habitat fragmentation rather than southward and eastward migration as for the bovine ancestors. We finally detect 423 genes under positive selection between the wisent and bovine lineages, which shed a new light on the genome response to different living conditions (temperature, available food resource, and pathogen exposure) and on the key gene functions altered by the domestication process., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Three genes of the prion protein gene family are expressed in gonads. Comparative analyses of their expression patterns in mice and goats revealed constant expression of PRNP and SPRN in both species and in both male and female gonads, but with a weaker expression of SPRN. By contrast, expression of PRND was found to be sex-dimorphic, in agreement with its role in spermatogenesis. More importantly, our study revealed that PRND seems to be a key marker of foetal Leydig cells specifically in goats, suggesting a yet unknown role for its encoded protein Doppel during gonadal differentiation in nonrodent mammals.

Unlabelled: Mammalian prions are proteinaceous infectious agents composed of misfolded assemblies of the host-encoded, cellular prion protein (PrP). Physiologically, the N-terminal polybasic region of residues 23 to 31 of PrP has been shown to be involved in its endocytic trafficking and interactions with glycosaminoglycans or putative ectodomains of membrane-associated proteins. Several recent reports also describe this PrP region as important for the toxicity of mutant prion proteins and the efficiency of prion propagation, both in vitro and in vivo. The question remains as to whether the latter observations made with mouse PrP and mouse prions would be relevant to other PrP species/prion strain combinations given the dramatic impact on prion susceptibility of minimal amino acid substitutions and structural variations in PrP. Here, we report that transgenic mouse lines expressing ovine PrP with a deletion of residues 23 to 26 (KKRP) or mutated in this N-terminal region (KQHPH instead of KKRPK) exhibited a variable, strain-dependent susceptibility to prion infection with regard to the proportion of affected mice and disease tempo relative to findings in their wild-type counterparts. Deletion has no major effect on 127S scrapie prion pathogenesis, whereas mutation increased by almost 3-fold the survival time of the mice. Deletion marginally affected the incubation time of scrapie LA19K and ovine bovine spongiform encephalopathy (BSE) prions, whereas mutation caused apparent resistance to disease., Importance: Recent reports suggested that the N-terminal polybasic region of the prion protein could be a therapeutic target to prevent prion propagation or toxic signaling associated with more common neurodegenerative diseases such as Alzheimer's disease. Mutating or deleting this region in ovine PrP completes the data previously obtained with the mouse protein by identifying the key amino acid residues involved., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: The advent and democratization of next generation sequencing and genotyping technologies lead to a huge amount of data for the characterization of population genetic diversity in model and non model-species. However, efficient storage, management, cross-analyzing and exploration of such dense genotyping datasets remain challenging. This is particularly true for the bovine species where many SNP datasets have been generated in various cattle populations with different genotyping tools., Description: We developed WIDDE, a Web-Interfaced Next Generation Database that stands as a generic tool applicable to a wide range of species and marker types ( http://widde.toulouse.inra.fr). As a first illustration, we hereby describe its first version dedicated to cattle biodiversity, which includes a large and evolving cattle genotyping dataset for over 750,000 SNPs available on 129 (89 public) different cattle populations representative of the world-wide bovine genetic diversity and on 7 outgroup bovid species. This version proposes an optional marker and individual filtering step, an export of genotyping data in different popular formats, and an exploration of genetic diversity through a principal component analysis. Users can also explore their own genotyping data together with data from WIDDE, assign their samples to WIDDE populations based on distance assignment method and supervised clustering, and estimate their ancestry composition relative to the populations represented in the database., Conclusion: The cattle version of WIDDE represents to our knowledge the first database dedicated to cattle biodiversity and SNP genotyping data that will be very useful for researchers interested in this field. As a generic tool applicable to a wide range of marker types, WIDDE is overall intended to the genetic diversity exploration of any species and will be extended to other species shortly. The structure makes it easy to include additional output formats and new tools dedicated to genetic diversity exploration.

Cattle commonly raised in Thailand have characteristics of Bos indicus (zebu). We do not know when or how cattle domestication in Thailand occurred, and so questions remain regarding their origins and relationships to other breeds. We obtained genome-wide SNP genotypic data of 28 bovine individuals sampled from four regions: North (Kho-Khaolampoon), Northeast (Kho-Isaan), Central (Kho-Lan) and South (Kho-Chon) Thailand. These regional varieties have distinctive traits suggestive of breed-like genetic variations. From these data, we confirmed that all four Thai varieties are Bos indicus and that they are distinct from other indicine breeds. Among these Thai cattle, a distinctive ancestry pattern is apparent, which is the purest within Kho-Chon individuals. This ancestral component is only present outside of Thailand among other indicine breeds in Southeast Asia. From this pattern, we conclude that a unique Bos indicus ancestor originated in Southeast Asia, and native Kho-Chon Thai cattle retain the signal of this ancestry with limited admixture of other bovine ancestors.

Based on its developmental pattern of expression, early studies suggested the implication of the mammalian Prion protein PrP, a glycosylphosphatidylinositol-anchored ubiquitously expressed and evolutionary conserved glycoprotein encoded by the Prnp gene, in early embryogenesis. However, gene invalidation in several species did not result in obvious developmental abnormalities and it was only recently that it was associated in mice with intra-uterine growth retardation and placental dysfunction. A proposed explanation for this lack of easily detectable developmental-related phenotype is the existence in the genome of one or more gene (s) able to compensate for the absence of PrP. Indeed, two other members of the Prnp gene family have been recently described, Doppel and Shadoo, and the consequences of their invalidation alongside that of PrP tested in mice. No embryonic defect was observed in mice depleted for Doppel and PrP. Interestingly, the co-invalidation of PrP and Shadoo in two independent studies led to apparently conflicting observations, with no apparent consequences in one report and the observation of a developmental defect of the ectoplacental cone that leads to early embryonic lethality in the other. This short review aims at summarizing these recent, apparently conflicting data highlighting the related biological questions and associated implications in terms of animal and human health.

Background: Modern cattle originate from populations of the wild extinct aurochs through a few domestication events which occurred about 8,000 years ago. Newly domesticated populations subsequently spread worldwide following breeder migration routes. The resulting complex historical origins associated with both natural and artificial selection have led to the differentiation of numerous different cattle breeds displaying a broad phenotypic variety over a short period of time., Methodology/principal Findings: This study gives a detailed assessment of cattle genetic diversity based on 1,121 individuals sampled in 47 populations from different parts of the world (with a special focus on French cattle) genotyped for 44,706 autosomal SNPs. The analyzed data set consisted of new genotypes for 296 individuals representing 14 French cattle breeds which were combined to those available from three previously published studies. After characterizing SNP polymorphism in the different populations, we performed a detailed analysis of genetic structure at both the individual and population levels. We further searched for spatial patterns of genetic diversity among 23 European populations, most of them being of French origin, under the recently developed spatial Principal Component analysis framework., Conclusions/significance: Overall, such high throughput genotyping data confirmed a clear partitioning of the cattle genetic diversity into distinct breeds. In addition, patterns of differentiation among the three main groups of populations--the African taurine, the European taurine and zebus--may provide some additional support for three distinct domestication centres. Finally, among the European cattle breeds investigated, spatial patterns of genetic diversity were found in good agreement with the two main migration routes towards France, initially postulated based on archeological evidence.

Susceptibility to scrapie is mainly controlled by point mutations at the PRNP locus. However, additional quantitative trait loci (QTL) have been identified across the genome including a region in OAR18. The gene which encodes the inducible form of the cytoplasmic Hsp90 chaperone (HSP90AA1) maps within this region and seems to be associated with the resistance/susceptibility to scrapie in sheep. Here, we have analyzed several polymorphisms which were previously described in the ovine HSP90AA1 5' flanking region and in intron 10 in two naturally scrapie infected Romanov sheep populations. First, we have studied 58 ARQ/VRQ animals pertaining to the sire family where the QTL influencing scrapie incubation period in OAR18 was detected. We have found a significant association between polymorphisms localized at -660 and -528 in the HSP90AA1 5' flanking region and the scrapie incubation period. These two polymorphisms have also been studied in a second sample constituted by 62 VRQ/VRQ sheep showing an extreme incubation period. Results are concordant with the first dataset. Finally, we have studied the HSP90AA1 expression in scrapie and control animals (N = 41) with different HSP90AA1 genotypes by real time PCR on blood samples. The HSP90AA1 expression rate was equivalent in CC(-600)AA(-528) and CG(-600)AG(-528) scrapie resistant animals (ARR/ARR) and was higher in their CC(-600)AA(-528) than in their CG(-600)AG(-528) scrapie susceptible counterparts (VRQ/VRQ). Our results support the hypothesis that the ovine HSP90AA1 gene acts as a modulator of scrapie susceptibility, contributing to the observed differences in the incubation period of scrapie infected animals with the same PRNP genotype.

Background: Since 2002, active surveillance programmes have detected numerous atypical scrapie (AS) and classical scrapie cases (CS) in French sheep with almost all the PrP genotypes. The aim of this study was 1) to quantify the genetic risk of AS in French sheep and to compare it with the risk of CS, 2) to quantify the risk of AS associated with the increase of the ARR allele frequency as a result of the current genetic breeding programme against CS., Methods: We obtained genotypes at codons 136, 141, 154 and 171 of the PRNP gene for representative samples of 248 AS and 245 CS cases. We used a random sample of 3,317 scrapie negative animals genotyped at codons 136, 154 and 171 and we made inferences on the position 141 by multiple imputations, using external data. To estimate the risk associated with PrP genotypes, we fitted multivariate logistic regression models and we estimated the prevalence of AS for the different genotypes. Then, we used the risk of AS estimated for the ALRR-ALRR genotype to analyse the risk of detecting an AS case in a flock homogenous for this genotype., Results: Genotypes most at risk for AS were those including an AFRQ or ALHQ allele while genotypes including a VLRQ allele were less commonly associated with AS. Compared to ALRQ-ALRQ, the ALRR-ALRR genotype was significantly at risk for AS and was very significantly protective for CS. The prevalence of AS among ALRR-ALRR animals was 0.6 per thousand and was not different from the prevalence in the general population., Conclusion: In conclusion, further selection of ALRR-ALRR animals will not result in an overall increase of AS prevalence in the French sheep population although this genotype is clearly susceptible to AS. However the probability of detecting AS cases in flocks participating in genetic breeding programme against CS should be considered.

Although susceptibility to scrapie is largely controlled by the PrP gene, the role of other genes that affect scrapie resistance in sheep is now confirmed. Following the detection of quantitative trait loci (QTL) on chromosomes 6 and 18 in a half-sib family with an ARQ/VRQ susceptible PrP genotype, the whole pedigree of a naturally infected flock was investigated to confirm these QTL regions in different PrP genotypes. The present study has allowed us to confirm the QTL on chromosome 18, and to demonstrate the QTL effects in several PrP genotypes.

Background: The recent settlement of cattle in West Africa after several waves of migration from remote centres of domestication has imposed dramatic changes in their environmental conditions, in particular through exposure to new pathogens. West African cattle populations thus represent an appealing model to unravel the genome response to adaptation to tropical conditions. The purpose of this study was to identify footprints of adaptive selection at the whole genome level in a newly collected data set comprising 36,320 SNPs genotyped in 9 West African cattle populations., Results: After a detailed analysis of population structure, we performed a scan for SNP differentiation via a previously proposed Bayesian procedure including extensions to improve the detection of loci under selection. Based on these results we identified 53 genomic regions and 42 strong candidate genes. Their physiological functions were mainly related to immune response (MHC region which was found under strong balancing selection, CD79A, CXCR4, DLK1, RFX3, SEMA4A, TICAM1 and TRIM21), nervous system (NEUROD6, OLFM2, MAGI1, SEMA4A and HTR4) and skin and hair properties (EDNRB, TRSP1 and KRTAP8-1)., Conclusion: The main possible underlying selective pressures may be related to climatic conditions but also to the host response to pathogens such as Trypanosoma(sp). Overall, these results might open the way towards the identification of important variants involved in adaptation to tropical conditions and in particular to resistance to tropical infectious diseases.

Effective selection on the PrP gene has been implemented since October 2001 in all French sheep breeds. After four years, the ARR "resistant" allele frequency increased by about 35% in young males. The aim of this study was to evaluate the impact of this strong selection on genetic variability. It is focussed on four French sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3-4 years later. Genetic variability was assessed using genealogical and molecular data (29 microsatellite markers). The expected loss of genetic variability on the PrP gene was confirmed. Moreover, among the five markers located in the PrP region, only the three closest ones were affected. The evolution of the number of alleles, heterozygote deficiency within population, expected heterozygosity and the Reynolds distances agreed with the criteria from pedigree and pointed out that neutral genetic variability was not much affected. This trend depended on breed, i.e. on their initial states (population size, PrP frequencies) and on the selection strategies for improving scrapie resistance while carrying out selection for production traits.

Scrapie is a transmissible spongiform encephalopathy in sheep and goats. Susceptibility to this neurodegenerative disease is mainly controlled by point mutations at the PRNP locus. Other genes, apart from PRNP, have been reported to modulate resistance/susceptibility to scrapie. On the basis of several studies in Alzheimer and different transmissible spongiform encephalopathy models, HSP90AA1 was chosen as a putative positional and functional candidate gene that might be involved in the polygenic variance mentioned above. In the present work, the ovine HSP90AA1 gene including the promoter and other regulatory regions has been isolated and characterized. Several sequence polymorphisms have also been identified. FISH-mapping localized the HSP90AA1 gene on ovine chromosome OAR19q24dist, which was confirmed by linkage analysis. This chromosome region has been shown to include a quantitative trait loci (QTL) for scrapie incubation period in sheep. Expression analyses were carried out in spleen and cerebellum samples. No differences in the expression of the HSP90AA1 gene were found in any of these tissues (p > 0.05) between control and infected animal samples. Nevertheless, association analyses revealed that several polymorphisms in the 5' and 3' regions of the HSP90AA1 gene were differentially distributed among animals with different responses to scrapie infection. Thus, results presented here support the hypothesis that HSP90AA1 could be a positional and functional candidate gene modulating the response to scrapie in sheep.

To evaluate and compare the extent of LD in cattle, 1536 SNPs, mostly localized on BTA03, were detected in silico from available sequence data using two different methods and genotyped on samples from 14 distinct breeds originating from Europe and Africa. Only 696 SNPs could be validated, confirming the importance of trace-quality information for the in silico detection. Most of the validated SNPs were informative in several breeds and were used for a detailed description of their genetic structure and relationships. Results obtained were in agreement with previous studies performed on microsatellite markers and using larger samples. In addition, the majority of the validated SNPs could be mapped precisely, reaching an average density of one marker every 311 kb. This allowed us to analyze the extent of LD in the different breeds. Decrease of LD with physical distance across breeds revealed footprints of ancestral LD at short distances (<10 kb). As suggested by the haplotype block structure, these ancestral blocks are organized, within a breed, into larger blocks of a few hundred kilobases. In practice, such a structure similar to that already reported in dogs makes it possible to develop a chip of <300,000 SNPs, which should be efficient for mapping purposes in most cattle breeds.

Working with weakly congruent markers means that consensus genetic structuring of populations requires methods explicitly devoted to this purpose. The method, which is presented here, belongs to the multivariate analyses. This method consists of different steps. First, single-marker analyses were performed using a version of principal component analysis, which is designed for allelic frequencies (%PCA). Drawing confidence ellipses around the population positions enhances %PCA plots. Second, a multiple co-inertia analysis (MCOA) was performed, which reveals the common features of single-marker analyses, builds a reference structure and makes it possible to compare single-marker structures with this reference through graphical tools. Finally, a typological value is provided for each marker. The typological value measures the efficiency of a marker to structure populations in the same way as other markers. In this study, we evaluate the interest and the efficiency of this method applied to a European and African bovine microsatellite data set. The typological value differs among markers, indicating that some markers are more efficient in displaying a consensus typology than others. Moreover, efficient markers in one collection of populations do not remain efficient in others. The number of markers used in a study is not a sufficient criterion to judge its reliability. "Quantity is not quality".

The genetic diversity of the casein locus in cattle was studied on the basis of haplotype analysis. Consideration of recently described genetic variants of the casein genes which to date have not been the subject of diversity studies, allowed the identification of new haplotypes. Genotyping of 30 cattle breeds from four continents revealed a geographically associated distribution of haplotypes, mainly defined by frequencies of alleles at CSN1S1 and CSN3. The genetic diversity within taurine breeds in Europe was found to decrease significantly from the south to the north and from the east to the west. Such geographic patterns of cattle genetic variation at the casein locus may be a result of the domestication process of modern cattle as well as geographically differentiated natural or artificial selection. The comparison of African Bos taurus and Bos indicus breeds allowed the identification of several Bos indicus specific haplotypes (CSN1S1*C-CSN2*A2-CSN3*AI / CSN3*H) that are not found in pure taurine breeds. The occurrence of such haplotypes in southern European breeds also suggests that an introgression of indicine genes into taurine breeds could have contributed to the distribution of the genetic variation observed.

This study was undertaken to determine the genetic structure, evolutionary relationships, and the genetic diversity among 18 local cattle breeds from Spain, Portugal, and France using 16 microsatellites. Heterozygosities, estimates of Fst, genetic distances, multivariate and diversity analyses, and assignment tests were performed. Heterozygosities ranged from 0.54 in the Pirenaica breed to 0.72 in the Barrosã breed. Seven percent of the total genetic variability can be attributed to differences among breeds (mean F(st) = 0.07; P<0.01). Five different genetic distances were computed and compared with no correlation found to be significantly different from 0 between distances based on the effective size of the population and those which use the size of the alleles. The Weitzman recursive approach and a multivariate analysis were used to measure the contribution of the breeds diversity. The Weitzman approach suggests that the most important breeds to be preserved are those grouped into two clusters: the cluster formed by the Mirandesa and Alistana breeds and that of the Sayaguesa and Tudanca breeds. The hypothetical extinction of one of those clusters represents a 17% loss of diversity. A correspondence analysis not only distinguished four breed groups but also confirmed results of previous studies classifying the important breeds contributing to diversity. In addition, the variation between breeds was sufficiently high so as to allow individuals to be assigned to their breed of origin with a probability of 99% for simulated samples.