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The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak's hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited ∼1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding.

African animal trypanosomosis is a parasitic blood disease transmitted by tsetse flies and is widespread in sub-Saharan Africa. West African taurine breeds have the ability, known as trypanotolerance, to limit parasitaemia and anaemia and remain productive in enzootic areas. Several quantitative trait loci (QTL) underlying traits related to trypanotolerance have been identified in an experimentally infected F2 population resulting from a cross between taurine and zebu cattle. Although this information is highly valuable, the QTL remain to be confirmed in populations subjected to natural conditions of infection, and the corresponding regions need to be refined. In our study, 360 West African cattle were phenotyped for the packed cell volume control under natural conditions of infection in south-western Burkina Faso. Phenotypes were assessed by analysing data from previous cattle monitored over 2 years in an area enzootic for trypanosomosis. We further genotyped for 64 microsatellite markers mapping within four previously reported QTL on BTA02, BTA04, BTA07 and BTA13. These data enabled us to estimate the heritability of the phenotype using the kinship matrix between individuals computed from genotyping data. Thus, depending on the estimators considered and the method used, the heritability of anaemia control ranged from 0.09 to 0.22. Finally, an analysis of association identified an allele of the MNB42 marker on BTA04 as being strongly associated with anaemia control, and a candidate gene, INHBA, as being close to that marker. (Resume d'auteur)

Cardiomyopathies are myocardial diseases that lead to cardiac dysfunction, heart failure, arrhythmia, and sudden death. In human medicine, cardiomyopathies frequently warrant heart transplantation in children and adults. Bovine dilated cardiomyopathy (BDCMP) is a heart muscle disorder that has been observed during the last 30 years in cattle of Holstein-Friesian origin. In Switzerland BDCMP affects Swiss Fleckvieh and Red Holstein breeds. BDCMP is characterized by a cardiac enlargement with ventricular remodeling and chamber dilatation. The common symptoms in affected animals are subacute subcutaneous edema, congestion of the jugular veins, and tachycardia with gallop rhythm. A cardiomegaly with dilatation and hypertrophy of all heart chambers, myocardial degeneration, and fibrosis are typical postmortem findings. It was shown that all BDCMP cases reported worldwide traced back to a red factor-carrying Holstein-Friesian bull, ABC Reflection Sovereign. An autosomal recessive mode of inheritance was proposed for BDCMP. Recently, the disease locus was mapped to a 6.7-Mb interval MSBDCMP06-BMS2785 on bovine Chr 18 (BTA18). In the present study the BDCMP locus was fine mapped by using a combined strategy of homozygosity mapping and association study. A BAC contig of 2.9 Mb encompassing the crucial interval was constructed to establish the correct marker order on BTA18. We show that the disease locus is located in a gene-rich interval of 1.0 Mb and is flanked by the microsatellite markers DIK3006 and MSBDCMP51.

Multi-copied gene families are prevalent in mammalian genomes, especially within the Y chromosome. Testis specific protein Y-encoded (TSPY) is present in variable copy number in many mammalian species. Previous studies have estimated that TSPY ranges from 50–200 copies in cattle. To examine TSPY localization on the Y chromosome we employed fluorescence in situ hybridization (FISH) and fiber-FISH. The results show a strong signal on the short arm of the Y chromosome (Yp). To investigate TSPY copy number we used relative real-time polymerase chain reaction (PCR) to analyze the DNA of 14 different cattle breeds. Variation both within and between breeds was observed. All breeds show significant variation in TSPY copy number among individual members. Brown Swiss (161 copies, CI = 133–195) had higher average levels of TSPY and Western Fjord Cattle (63 copies, CI = 45–86) had lower levels than some breeds. Overall, however, most breeds had a similar average TSPY copy number. The pooled average was 94 copies (CI = 88–100). The significance of the TSPY array remains uncertain, but as the function of TSPY is unraveled the purpose of the array may become clearer.

WWOX (WW domain-containing oxidoreductase) is the gene mapping at FRA16D HSA16q23.1, the second most active common fragile site in the human genome. In this study we characterized at a detailed molecular level WWOX in the bovine genome. First, we sequenced cDNA from various tissues and obtained evidence in support of a 9-exon structure for the gene, similar to the human gene. Then, we recovered BACs using exon tags and annotated the gene to a >1-Mb genomic region of BTA18 using the Btau 4.0 genome assembly as a reference, thus resolving an issue related to exon 9, which is not included in the genomic annotation of the gene in the Entrez database. Finally, BACs spanning WWOX were used as FISH probes to obtain comparative mapping of the gene in Bos taurus, Bubalus bubalis, Ovis aries and Capra hircus to BTA18q12.1, BBU18q13, OAR14q12.1 and CHI18q12.1, respectively. Our data show that the chromosomal location of WWOX is conserved between man and 4 major domesticated species. Moreover, the annotation of the bovine gene also suggests a highly conserved genomic arrangement, including number and size of introns.

Summary The purpose of this study was to map quantitative trait loci (QTL) influencing female fertility estimated by non-return rate (NRR) in the French dairy cattle breeds Prim’Holstein, Normande and Montbeliarde. The first step was a QTL detection study on NRR at 281 days after artificial insemination on 78 half-sib families including 4993 progeny tested bulls. In Prim’Holstein, three QTL were identified on Bos taurus chromosomes BTA01, BTA02 and BTA03 (p

We report an extended river buffalo (Bubalus bubalis, 2n = 50; BBU) cytogenetic map including 388 loci, of which 68 have been FISH-mapped on autosomes in the present study. Ovine and caprine BAC clones containing both type I loci (known genes) and type II loci (simple sequence repeats (SRs), microsatellite marker, sequence-tagged sites (STSs)), previously assigned to sheep chromosomes, have been localized on R-banded river buffalo chromosomes (BBU), which expands the cytogenetic map of this important domestic species and increases our knowledge of the physical organization of its genome. The loci mapped in the present study correspond to loci already localized on homoeologous cattle (and sheep) chromosomes and chromosome bands, further confirming the high degree of chromosome homoeologies among bovids. The comparison of the integrated cytogenetic maps of BBU2p/BBU10 and BBU5p/BBU16 with those of human chromosomes (HSA) 6 and 11, respectively, identified, at least, nine conserved chromosome segments in each case and complex rearrangements differentiating river buffalo (and cattle) and human chromosomes.

Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the heart muscle observed in Holstein-Friesian cattle over the last 30 years. There is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The objective of this study was to genetically map BDCMP, with the ultimate goal of identifying the causative mutation. A whole-genome scan using 199 microsatellite markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The interval containing the BDCMP locus was confirmed by multipoint linkage analysis using the software loki. The interval is about 6.7 Mb on the bovine genome sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a possible positional and a functional candidate for BDCMP given its involvement in a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle revealed no mutation in the coding sequence, but there was a G-to-A transition in intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP. Considering the high density of genes on the homologous region of HSA19, further refinement of the interval on BTA18 containing the BDCMP locus is needed.

Presented herein is an updated sheep cytogenetic map that contains 452 loci (291 type I and 161 type II) assigned to specific chromosome bands or regions on standard R-banded ideograms. This map, which significantly extends our knowledge of the physical organization of the ovine genome, includes new assignments for 88 autosomal loci, including 74 type I loci (known genes) and 14 type II loci (SSRs/microsatellite marker/STSs), by FISH-mapping and R-banding. Comparison of the ovine map to the cattle and goat cytogenetic maps showed that common loci were located within homologous chromosomes and chromosome bands, confirming the high level of conservation of autosomes among ruminant species. Eleven loci that were FISH-mapped in sheep (B3GAT2, ASCC3, RARSL, BRD2, POLR1C, PPP2R5D, TNRC5, BAT2, BAT4, CDC5L and OLA-DRA) are unassigned in cattle and goat. Eleven other loci (D3S32, D1S86, BMS2621, SFXN5, D5S3, D5S68, CSKB1, D7S49, D9S15, D9S55 and D29S35) were assigned to specific ovine chromosome (OAR) bands but have only been assigned to chromosomes in cattle and goat.

Caprine-like Generalized Hypoplasia Syndrome (SHGC) is an autosomal-recessive disorder in Montbéliarde cattle. Affected animals present a wide range of clinical features that include the following: delayed development with low birth weight, hind limb muscular hypoplasia, caprine-like thin head and partial coat depigmentation. Here we show that SHGC is caused by a truncating mutation in the CEP250 gene that encodes the centrosomal protein C-Nap1. This mutation results in centrosome splitting, which neither affects centriole ultrastructure and duplication in dividing cells nor centriole function in cilium assembly and mitotic spindle organization. Loss of C-Nap1-mediated centriole cohesion leads to an altered cell migration phenotype. This discovery extends the range of loci that constitute the spectrum of autosomal primary recessive microcephaly (MCPH) and Seckel-like syndromes., SHGC syndrome affects cattle and has clinical features similar to human Seckel syndrome. Here Floriot et al. identify the causative mutation in the centrosomal protein C-Nap1 that affects centriole cohesion and cell migration, extending the range of loci involved in human Seckel-like syndromes.

On the basis of fine mapping of a quantitative trait loci region of BTA3 for milk fat content, an examination of the comparative map between cattle and human indicates that the annexin 9 protein gene (ANXA9) and the fatty acid transport protein type 3 gene (SLC27A3) are two strong candidate genes. The objective of the present study is to isolate, map and characterize these genes and identify polymorphisms that could be further utilized in linkage or association studies. Furthermore, two new genes which are in the same region, cingulin protein gene (CGN) and lysophosphatidic acid phosphatase protein gene (ACP6) were studied. DNA fragments (869, 1778, 1933 and 2618 bp) corresponding to partial sequences of ACP6,CGN,ANXA9 and SLC27A3 genes were isolated. Direct sequencing of PCR products amplified from different cattle breeds revealed 1, 4, 4 and 2 SNPs for ACP6, CGN,ANXA9 and SLC27A3, respectively. For ANXA9 one SNP was located in exon 5 (A→G 951) resulting in an amino acid change from histidine to arginine. Finally, ACP6,CGN,ANXA9 and SLC27A3 genes were located on chromosome 3 between ILSTS096 and BMS819 markers, in a region in which quantitative trait loci (QTL) for several milk traits have been described.

GPAM maps in BTA26q22, where several QTLs affecting milk production, milk fat and protein content have been mapped. On the basis of the QTL location, the GPAM gene could be considered a good candidate gene for the mentioned traits. Glycerol-3-phosphate acyltransferase mitochondrial (GPAM) is the enzyme that catalyses the initial and committed step of glycerolipid synthesis and, therefore, it is a potential site for triacylglycerol synthesis regulation. In this study, the structure of the cDNA and the genomic DNA of the bovine GPAM gene were determined and the expression of its mRNA was studied. The cDNA of the gene was cloned by RT-PCR, 5′ and 3′ rapid amplification of cDNA ends. The GPAM mRNA sequence contains a 2,475-bp coding region and a 3,689-bp 3′ UTR. Its ORF encoded for an 825-amino acid protein and has an 89% homology with the coding regions of previously characterized mouse and human GPAM genes. The predicted amino acid sequence had an 89 and 93% similarity with mouse and human GPAM proteins, respectively. Using a 5′ RACE strategy, two different 5′ UTRs were cloned. Northern blot analysis confirmed the presence of two different transcripts. Adipose tissues and lung had the highest levels of GPAM mRNA expression, whereas it was barely detectable in liver. This expression pattern differs with those of non-ruminant animals where liver is one of the tissues with higher GPAM mRNA expression level.

Comparative FISH-mapping among Y chromosomes of cattle (Bos taurus, 2n = 60, BTA, submetacentric Y chromosome), zebu (Bos indicus, 2n = 60, BIN, acrocentric Y chromosome but with visible small p-arms), river buffalo (Bubalus bubalis, 2n = 50, BBU, acrocentric Y chromosome), sheep (Ovis aries, 2n = 54, OAR, small metacentric Y chromosome) and goat (Capra hircus, 2n = 60, CHI, Y-chromosome as in sheep) was performed to extend the existing cytogenetic maps and improve the understanding of karyotype evolution of these small chromosomes in bovids. C- and R-banding comparison were also performed and both bovine and caprine BAC clones containing the SRY, ZFY, UMN0504, UMN0301, UMN0304 and DYZ10 loci in cattle and DXYS3 and SLC25A6 in goat were hybridized on R-banded chromosomes by FISH. The main results were the following: (a) Y-chromosomes of all species show a typical distal positive C-band which seems to be located at the same region of the typical distal R-band positive; (b) the PAR is located at the telomeres but close to both R-band positive and ZFY in all species; (c) ZFY is located opposite SRYand on different arms of BTA, BIN, OAR/CHI Y chromosomes and distal (but centromeric to ZFY) in BBU-Y; (d) BTA-Y and BIN-Y differ as a result of a centromere transposition or pericentric inversion since they retain the same gene order along their distal chromosome regions and have chromosome arms of different size; (e) BTA-Y and BBU-Y differ in a pericentric inversion with a concomitant loss or gain of heterochromatin; (f) OAR/CHI-Y differs from BBU-Y for a pericentric inversion with a major loss of heterochromatin and from BTA and BIN for a centromere transposition followed by the loss of heterochromatin.

International audience; A comparative pathology and mapping strategy was used to initiate a study on two bovine genetic diseases: arthrogryposis-palatoschisis and progressive ataxia, which affect mainly Charolais cattle. Bibliographic studies provided information on the pathology of these diseases, which helped to define similar diseases in other species. Animals affected by bovine arthrogryposis-palatoschisis display similar symptoms to those of muscular dysgenesis, mouse mutants and animals with progressive ataxia to those of Long Evans Shaker rat mutants. Candidate regions are respectively human chromosome 1q32 (BTA16) containing the gene CACNA1S and human chromosome 18q23 (BTA24) containing the gene myelin basic protein (MBP). Primer pairs were designed for 15 loci around each candidate gene, in a region of about 20 megabases and were used to screen a bovine Bacterial Artificial Chromosome (BAC) library. Eighteen microsatellites were found in the identified BAC clones, 11 on BTA24 and seven on BTA16. The genes and microsatellites were mapped by radiation hybrid (RH) analysis and a RH map was obtained for each region with 18 new localizations on BTA16 and 23 on BTA24. Comparative human-bovine analysis of the MBP region shows a good conservation of gene order while that of the CACNA1S region shows several breakpoints.

Fatty acid synthesis differs considerably between monogastric and ruminant species. Fatty acid synthase (FASN) plays a central role in de novo lipogenesis in mammals. FASN has seven active sites which help to catalyse all the reaction steps in the conversion of acetyl-CoA and malonyl-CoA to palmitate. In this work, the bovine fatty acid synthase gene (FASN) was cloned, characterized and compared to the human and rat orthologs. Comparative analysis reveals evolutionarily conserved exon regions and gene flanking sequences. Analysis of the DNA sequence in the 5′ flanking region of the FASN bovine gene revealed a potential TATA box, CAAT box and 5 Sp1 binding sites located in a CpG island. RT-PCR and Western blot analysis showed that FASN expression was higher in brain, testis and adipose tissue than in liver and heart. The longer form of the FASN cDNA includes a 7,542-bp sequence which encodes a protein with 2,513 amino acids. An alternative transcript was discovered in bovine and ovine tissues devoid of part of exon 9. The removal of part of exon 9 by post-transcriptional splicing causes a frameshift in the open reading frame and results in a premature termination codon. We hypothesize that in ruminants, FASN may be regulated by the ratio between the two transcripts. The small transcript is mostly produced in tissues with low fatty acid synthesis.

Four microsatellite-containing bovine cosmids have been regionally localized by fluorescence in situ hybridization to bovine R-banded chromosome 29 (BTA29) and to the 1;29 translocated chromosomes. PCR-analyses of a somatic hybrid cell panel assigned the four microsatellites to synteny group U7. One of the cosmids (IDVGA7) has been previously mapped to G-banded BTA25 allowing to assign U7 to this chromosome. Hence, it is concluded that G-banded BTA25 corresponds to R-banded BTA29. The occurrence of other misleading nomenclatures for small bovine chromosomes is discussed.

A representational difference analysis was performed to identify genes expressed in the corpus luteum of cattle. The corpus luteum is an ovarian structure that is essential for the establishment and maintenance of pregnancy. Knowledge of gene expression and function of corpus luteum will be important to improve fertility in humans and domestic animals. Housekeeping genes were removed from the corpus luteum representation (tester) using skeletal muscle as the subtracting agent (driver). A total of 80 clones of the final subtraction product were analysed by sequencing and 11 new bovine gene sequences were identified (pBTCL1-11). The sequences were mapped to segments of 10 different chromosomes using a somatic cell hybrid panel and a radiation hybrid panel. With one exception the locations are in agreement with published comparative maps of cattle and man. Expression in corpus luteum was verified by RT-PCR for all the 11 clones.

Our on-going goal is to improve and update the comparative genome organization between cattle and man but also among the most detailed mammalian species genomes i.e. cattle, mouse, rat and pig. In this work, we localized 195 genes in cattle and checked all human/bovine non-concordant localizations found in the literature. Next, we compiled all the genes mapped in cattle, goat, sheep and pig (2,166) for which the human ortholog with its chromosomal position is known, added corresponding data in mouse and rat, and ordered the genes relatively to the human genome sequence. We estimate that our compilation provides bovine mapping information for about 89% of the human autosomes. Thus, a near complete, overall and detailed picture of the number, distribution and extent of bovine conserved syntenies (regardless of gene order) on human R-banded autosomes is proposed as well as a comparison with mouse, rat and pig genomes.

Sixty-four genomic BAC-clones mapping five type I (ADCYAP1, HRH1, IL3, RBP3B and SRY) and 59 type II loci, previously FISH-mapped to goat (63 loci) and cattle (SRY) chromosomes, were fluorescence in situ mapped to river buffalo R-banded chromosomes, noticeably extending the physical map of this species. All mapped loci from 26 bovine syntenic groups were located on homeologous chromosomes and chromosome regions of river buffalo and goat (cattle) chromosomes, confirming the high degree of chromosome homeologies among bovids. Furthermore, an improved cytogenetic map of the river buffalo with 293 loci from all 31 bovine syntenic groups is reported.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-2181-1) contains supplementary material, which is available to authorized users.

A comparative mapping approach was applied in order to refine the extent and the distribution of conserved segments between the long arm of human chromosome 10 (HSA10) and cattle chromosomes 26 and 28 (BTA26 and BTA28 respectively). Sixteen genes localised on the long arm of HSA10 were mapped using a bovine–hamster somatic cell hybrid panel: twelve represent new assignments in cattle; the four others are in agreement with previous published data. This study confirms and refines the boundaries of the disruption zones between HSA10 and, BTA26 and BTA28, at the level of the human cytogenetic band.

L. Iannuzzi, G. P. Di Meo , H. Hayes 2 , A. Perucatti, D. Incarnato , M. Gautier 2 & A. Eggen 2 1 National Research Council (CNR), IABBAM, Via Argine 1085, 80147 Naples, Italy; Tel: +39-081-5964977; Fax: +39-081-5965291; E-mail: L.Iannuzzi@iabbam.na.cnr.it ; 2 Research Center, INRA, Laboratory of Genetics and Cytogenetics, Department of Animal Genetics, 78352 Jouy-en-Josa,s, France *Technical assistance and microscope image processing

We have sequenced to high levels of accuracy 714-kb and 233-kb regions of the mouse and bovine X-inactivation centers (Xic), respectively, centered on the Xist gene. This has provided the basis for a fully annotated comparative analysis of the mouse Xic with the 2.3-Mb orthologous region in human and has allowed a three-way species comparison of the core central region, including theXist gene. These comparisons have revealed conserved genes, both coding and noncoding, conserved CpG islands and, more surprisingly, conserved pseudogenes. The distribution of repeated elements, especially LINE repeats, in the mouse Xic region when compared to the rest of the genome does not support the hypothesis of a role for these repeat elements in the spreading of X inactivation. Interestingly, an asymmetric distribution of LINE elements on the two DNA strands was observed in the three species, not only within introns but also in intergenic regions. This feature is suggestive of important transcriptional activity within these intergenic regions. In silico prediction followed by experimental analysis has allowed four new genes, Cnbp2, Ftx, Jpx, and Ppnx, to be identified and novel, widespread, complex, and apparently noncoding transcriptional activity to be characterized in a region 5′ of Xist that was recently shown to attract histone modification early after the onset of X inactivation.[The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ421478, AJ421479, AJ421480, andAJ421481. Online supplemental data are available athttp://pbil.univ-lyon1.fr/datasets/Xic2002/data.html andwww.genome.org.]

A series of 31 marker genes (one per chromosome) were localized precisely to both Q- and R-banded bovine chromosomes by fluorescence in situ hybridization (FISH), as a contribution to the revised chromosome nomenclature of the three major domestic bovidae (cattle, sheep and goat). All marker genes except one (LDHA) are taken from the Texas Nomenclature of the cattle karyotype published in 1996. Homologous probes for each marker gene were obtained by screening a bovine BAC library by PCR with specific primer pairs. After labeling with biotin, each probe preparation was divided into two fractions and hybridized to bovine chromosomes identified either by Q or R banding. Clear signals and good quality band patterns were observed in all cases. Results of the two series of hybridizations are totally concordant both for Q and R band chromosome numbering and precise band localization. This work permits an unambiguous correlation between the Q/G- and R-banded 31 bovine chromosomes, including chromosomes 25, 27 and 29 which remained unresolved in the Texas Nomenclature (1996). Hybridization of the chromosome 29 marker gene to metaphase spreads from a 1;29 Robertsonian translocation bull carrier showed a positive signal on the short arm of this rearranged chromosome, confirming that the numbering of this long-known translocation in cattle is correct when referring to the Texas Nomenclature (1996). Taking into account that cattle, goat and sheep have very similar banded karyotypes, the data presented here will help to establish a definite and complete reference chromosome nomenclature for these species.

A clone for the bovine gene MAP1B was isolated from a bovine cosmid library with a probe obtained by cross-species PCR. The single positive cosmid clone was localized by FISH to chromosome region 20q14. Analysis of the cosmid revealed the presence of a microsatellite motif with a two-allele polymorphism detectable by PCR amplification of genomic DNA. However, the analysis of this polymorphism in a bovine family affected by SMA indicated absence of very close linkage of the phenotype for bovine SMA with MAP1B.

Four bovine BAC clones (0494F01, 0069D07, 0060B06, and 0306A12) containing MUC1, as confirmed by mapping MUC1 on a RH3000 radiation hybrid panel, were hybridised on R-banded chromosomes of cattle (BTA), river buffalo (BBU), sheep (OAR) and goat (CHI). MUC1 was FISH-mapped on BTA3q13, BBU6q13, OAR1p13 and CHI3q13 and both chromosomes and chromosome bands were homoeologous confirming the high degree of chromosome homoeologies among bovids and adding more information on the pericentromeric regions of these species’ chromosomes. Indeed, MUC1 was more precisely assigned to BTA3 and assigned for the first time to BBU6, OAR1p and CHI3. Moreover, detailed and improved cytogenetic maps of BTA3, CHI3, OAR1p and BBU6 are shown and compared with HSA1.

Chantier qualité GA; Despite massive research efforts, the molecular etiology of bovine polledness and the developmental pathways involved in horn ontogenesis are still poorly understood. In a recent article, we provided evidence for the existence of at least two different alleles at the Polled locus and identified candidate mutations for each of them. None of these mutations was located in known coding or regulatory regions, thus adding to the complexity of understanding the molecular basis of polledness. We confirm previous results here and exhaustively identify the causative mutation for the Celtic allele (PC) and four candidate mutations for the Friesian allele (PF). We describe a previously unreported eyelash-and-eyelid phenotype associated with regular polledness, and present unique histological and gene expression data on bovine horn bud differentiation in fetuses affected by three different horn defect syndromes, as well as in wild-type controls. We propose the ectopic expression of a lincRNA in PC/p horn buds as a probable cause of horn bud agenesis. In addition, we provide evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci. Our results represent a first and important step in understanding the genetic pathways and key process involved in horn bud differentiation in Bovidae.

During the twentieth century, with the rapid advancement in elucidating the mechanisms of heredity and in technologies giving direct access to the blueprint of an organism, the basis for a new discipline called ‘genomics’ was established. Phenotype differences between animals can now be studied from a completely different point of view, namely the nucleotide sequence. A major goal of genomics is to gain an exhaustive understanding of the structure and the function of genomes through a detailed molecular characterization of whole genomes. Therefore, genomic approaches can help in the dissection of the genetic components of a qualitative, quantitative and complex trait, and thus new possible applications for animal selection can be considered in the near future (for example, marker-assisted selection).

Summary Bovine BAC clones containing the 31 genes, referred to as the Texas markers used earlier to definitively assign the 31 bovine syntenic groups (U) to cattle chromosomes, were mapped by fluorescent in situ hybridization to sheep and goat R-banded chromosomes according to ISCNDB2000. All 31 markers were localized on homoeologous chromosomes and chromosome bands of the two species in agreement with previous localizations obtained both in cattle and river buffalo, definitively confirming chromosome homoeologies between Caprinae and Bovinae. In addition, we have extended physical maps of sheep and goat as 11 genes (HSD3B1, INHBA, CSN10, IGF2R, PIGR, MAP1B, DSC1, ELN, TNFRSF6, CGN1, IGF2) and 14 genes (SOD1, HSD3B1, CSN10, IGF2R, RB1, TG, PIGR, MAP1B, IGH@, LTF, DSC1, TNFRSF6, CGN1, IGF2) were assigned for the first time to goat and sheep chromosomes, respectively.

Background Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases. Results In this study using the high density BovineHD SNP array, we performed high resolution CNV analyses on both Btau_4.0 and UMD3.1 with 674 animals of 27 cattle breeds. We first compared CNV results derived from these two different SNP array platforms on Btau_4.0. With two thirds of the animals shared between studies, on Btau_4.0 we identified 3,346 candidate CNV regions representing 142.7 megabases (~4.70%) of the genome. With a similar total length but 5 times more event counts, the average CNVR length of current Btau_4.0 dataset is significantly shorter than the previous one (42.7 kb vs. 205 kb). Although subsets of these two results overlapped, 64% (91.6 megabases) of current dataset was not present in the previous study. We also performed similar analyses on UMD3.1 using these BovineHD SNP array results. Approximately 50% more and 20% longer CNVs were called on UMD3.1 as compared to those on Btau_4.0. However, a comparable result of CNVRs (3,438 regions with a total length 146.9 megabases) was obtained. We suspect that these results are due to the UMD3.1 assembly's efforts of placing unplaced contigs and removing unmerged alleles. Selected CNVs were further experimentally validated, achieving a 73% PCR validation rate, which is considerably higher than the previous validation rate. About 20-45% of CNV regions overlapped with cattle RefSeq genes and Ensembl genes. Panther and IPA analyses indicated that these genes provide a wide spectrum of biological processes involving immune system, lipid metabolism, cell, organism and system development. Conclusion We present a comprehensive result of cattle CNVs at a higher resolution and sensitivity. We identified over 3,000 candidate CNV regions on both Btau_4.0 and UMD3.1, further compared current datasets with previous results, and examined the impacts of genome assemblies on CNV calling.

Cattle microsatellite clones (136) were isolated from cosmid (10) and plasmid (126) libraries and sequenced. The dinucleotide repeats were studied in each of these sequences and compared with dinucleotide repeats found in other vertebrate species where information was available. The distribution in cattle was similar to that described for other mammals, such as rat, mouse, pig, or human. A major difference resides in the number of sequences present in the bovine genome, which seemed at best one-third as large as in other species. Oligonucleotide primers (117 pairs) were synthesized, and a PCR product of expected size was obtained for 88 microsatellite sequences (75%). Synteny or chromosome assignment was searched for each locus with PCR amplification on a panel of 36 hamster/bovine somatic cell hybrids. Of our bovine microsatellites, eighty-six could be assigned to synteny groups of chromosomes. In addition, 10 other microsatellites--HEL 5, 6, 9, 11, 12, 13 (Kaukinen and Varvio 1993), HEL 4, 7, 14, 15--as well as the microsatellite found in the kappa-casein gene (Fries et al. 1990) were mapped on the hybrids. Microsatellite polymorphism was checked on at least 30 unrelated animals of different breeds. Almost all the autosomal and X Chr microsatellites displayed polymorphism, with the number of alleles varying between two and 44. We assume that these microsatellites could be very helpful in the construction of a primary public linkage map of the bovine genome, with an aim of finding markers for Economic Trait Loci (ETL) in cattle.

Chantier qualité GA; The developmental pathways involved in horn development are complex and still poorly understood. Here we report the description of a new dominant inherited syndrome in the bovine Charolais breed that we have named type 2 scurs. Clinical examination revealed that, despite a strong phenotypic variability, all affected individuals show both horn abnormalities similar to classical scurs phenotype and skull interfrontal suture synostosis. Based on a genome-wide linkage analysis using Illumina BovineSNP50 BeadChip genotyping data from 57 half-sib and full-sib progeny, this locus was mapped to a 1.7 Mb interval on bovine chromosome 4. Within this region, the TWIST1 gene encoding a transcription factor was considered as a strong candidate gene since its haploinsufficiency is responsible for the human Saethre-Chotzen syndrome, characterized by skull coronal suture synostosis. Sequencing of the TWIST1 gene identified a c.148_157dup (p.A56RfsX87) frame-shift mutation predicted to completely inactivate this gene. Genotyping 17 scurred and 20 horned founders of our pedigree as well as 48 unrelated horned controls revealed a perfect association between this mutation and the type 2 scurs phenotype. Subsequent genotyping of 32 individuals born from heterozygous parents showed that homozygous mutated progeny are completely absent, which is consistent with the embryonic lethality reported in Drosophila and mouse suffering from TWIST1 complete insufficiency. Finally, data from previous studies on model species and a fine description of type 2 scurs symptoms allowed us to propose different mechanisms to explain the features of this syndrome. In conclusion, this first report on the identification of a potential causal mutation affecting horn development in cattle offers a unique opportunity to better understand horn ontogenesis.

International audience

Cette étude a été réalisée en 2009. Les affiliations indiquées sont celles des auteurs à cette époque. Aujourd’hui l’UNCEIA est devenue ALLICE, F. Guillaume travaille chez Evolution, M.Y. Boscher à l’INRA, L. Journaux à IDELE, A. Eggen à Illumina, et D. Dupassieux est agriculteur.; National audience; Genomic selection was simulated in a large dairy cattle population in comparison with a breeding scheme based on bull progeny-testing. The maximum increase of genetic gain (about 80% without cost increase) was obtained when bull sires, in much larger number, were selected only based on genomic information, without progeny-testing. In spite of a shorter generation interval, annual inbreeding and coancestry rates were decreased because these bull sires were much more numerous than in the reference scheme. The general recommendation to the AI industry is to pick-up a quite large batch of commercial sires (for breeding regular females) within the set of genomic bull sires, in total contrast with the conventional practice where few bull sires are a selected set of commercial sires, themselves in limited number because selected after progeny-testing. These results obtained in 2009 paved the way for a sustainable genomic selection of French dairy cattle, and are still up to date. Indeed, it is critical for selection and dairy cattle production sustainability to maintain a high enough effective size of the breeds to limit the inbreeding trend. An overview of the first years of activity shows that these recommendations have been well respected on average.; Cet article présente une simulation de sélection génomique dans une grande population de bovins laitiers en comparaison à un programme basé sur le testage des taureaux sur descendance. L’accroissement de progrès génétique est maximum (au moins 80% sans augmentation de coût) quand les pères à taureaux, dont les effectifs sont en forte augmentation, sont sélectionnés uniquement sur information génomique, sans testage sur descendance. Avec ce nombre élevé de pères à taureaux, les coefficients de consanguinité et de parenté diminuent, contrairement à ce qu’on aurait pu craindre compte tenu du raccourcissement de l’intervalle entre générations. Au niveau des éleveurs, la recommandation est de choisir les taureaux d’insémination de service (pères des femelles) en nombre suffisant dans l’ensemble des nombreux pères à taureaux génomiques, en opposition complète avec la pratique générale qui, jusqu’en 2009, consistait au contraire à sélectionner un nombre relativement réduit de taureaux de service parmi les taureaux testés et un nombre encore plus faible de pères à taureaux parmi les taureaux de service. Ces résultats, obtenus en 2009, ont jeté les bases de la gestion des populations bovines laitières en France en sélection génomique, mais ils restent tout à fait d’actualité aujourd’hui. Il est en effet essentiel pour la durabilité de la sélection et de la production que le nombre efficace de reproducteurs soit élevé pour limiter l’augmentation de la consanguinité. L’observation des premières années d’application montre que ces préconisations sont relativement bien suivies en moyenne.

Background Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Results Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc) reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families). Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4%) and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%). This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Conclusion Our results suggest the existence of unknown genetics factors modifying the expression of the scurs locus in double heterozygous Hereford and Angus males. The specific inheritance pattern of the scurs locus in the French Charolais breed represents an opportunity to map this gene and to identify the molecular mechanisms regulating the growth of horns in cattle.

International audience; Breeding indigenous African taurine cattle tolerant to trypanosomosis is a straightforward approach to control costs generated by this disease. A recent study identified quantitative trait loci (QTL) underlying trypanotolerance traits in experimental crosses between tolerant N'Dama and susceptible Boran zebu cattle. As trypanotolerance is thought to result from local adaptation of indigenous cattle breeds, we propose an alternative and complementary approach to study the genetic architecture of this trait, based on the identification of selection signatures within QTL or candidate genes. A panel of 92 microsatellite markers was genotyped on 509 cattle belonging to four West African trypanotolerant taurine breeds and 10 trypanosusceptible European or African cattle breeds. Some of these markers were located within previously identified QTL regions or candidate genes, while others were chosen in regions assumed to be neutral. A detailed analysis of the genetic structure of these different breeds was carried out to confirm a priori grouping of populations based on previous data. Tests based on the comparison of the observed heterozygosities and variances in microsatellite allelic size among trypanotolerant and trypanosusceptible breeds led to the identification of two significantly less variable microsatellite markers. BM4440, one of these two outlier loci, is located within the confidence interval of a previously described QTL underlying a trypanotolerance-related trait. Detection of selection signatures appears to be a straightforward approach for unravelling the molecular determinism of trypanosomosis pathogenesis. We expect that a whole genome approach will help confirm these results and achieve a higher resolving power.

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production. Fil: Bovine Genome Sequencing and Analysis Consortium. Bovine Genome Sequencing And Analysis Consortium; Estados Unidos Fil: Amadio, Ariel Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; Argentina Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; Argentina

International audience; The growth hormone secretagogue receptor (GHSR) is involved in the regulation of energetic homeostasis and GH secretion. In this study, the bovine GHSR gene was mapped to BTA1 between BL26 and BMS4004. Two different bovine GHSR CDS (GHSR1a and GHSR1b) were sequenced. Six polymorphisms (five SNPs and one 3-bp indel) were also identified, three of them leading to amino acid variations L24V, D194N, and Del R242. These variations are located in the extracellular N-terminal end, the exoloop 2, and the cytoloop 3 of the receptor, respectively.

International audience; Summary Caprine-like Generalized Hypoplasia Syndrome (or SHGC) is a new hereditary disorder described in the Montbe´liarde breed. We report here the characterization of this new disease, based on the visual examination of animals affected by SHGC, and on physiological and biochemical studies undertaken on samples of both SHGC and normal animals. Biological samples for more than 150 affected calves and their parents have been collected over the past 4 years within the framework of the Bovine Genetic Disease Observatory. First, pedigree analyses showed that the mode of inheritance is most probably autosomal recessive. Then, a genome scan with 113 animals and 140 microsatellite markers revealed a single locus within a 35-cM region on bovine chromosome 13. Genotypes of 261 animals for 18 new microsatellite markers from the region confirmed the localization of the disorder to a 6-cM interval. Finally, based on the analysis of haplotypes in 463 Montbe´liarde sires, we estimated the frequency of the SHGC mutated allele in the population and could propose a strategy for the systematic eradication of this disorder in the near future.