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Background: Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH)., Results: We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHR and the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content., Conclusions: These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance, MAP2K6 is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass weight, back fat thickness and marbling score in Korean beef cattle. Based on the confirmation process and literature search we deduce that XP-EHH is able to uncover numerous artificial selection targets in subpopulations of domesticated animals.

A whole-genome association study of milk production traits: milk yield, protein yield, fat yield, protein percentage, and fat percentage, was performed on the population of Braunvieh cattle. Five hundred and fifty-four progeny-tested bulls and 36,219 autosomal single nucleotide polymorphism (SNP) markers on 29 Bos taurus autosomes (BTA) were included in the analysis. A principal component analysis was conducted to adjust for the effect of population stratification in the analyzed data set. For the principal component analysis, genome-wide relationships between individuals were calculated. Three different criteria (Horn's test, Kaiser's criterion, and Jolliffe's criterion) were tested to determine the number of significant principal components. Estimation of putative associations between SNP and milk production traits was carried out using a linear regression model in R software (R Foundation for Statistical Computing, Vienna, Austria). Significant principal components, adjusting for population stratification separately for each criterion and family relationships and genotypes at individual SNP were included as fixed effects in the model. The inflation factor λ and quantile-quantile plots were calculated to compare how the different criteria deal with stratification in our mapping population. Based on the analyses on all of the aforementioned criteria, we can conclude that Jolliffe's criterion deals the best with population stratification. Furthermore, significance thresholds for a given genome-wide false discovery rate of 5% were estimated and used for specific traits. Three of the analyzed traits showed genome-wide significant association with SNP. Two SNP had an effect on milk yield on BTA4, 2 SNP affected fat yield on BTA14 and BTA23, and 1 SNP was associated with fat percent on BTA1. Single nucleotide polymorphisms identified in this study as associated with milk production traits will further contribute to the mapping of corresponding quantitative trait loci and investigation of the genes responsible for polymorphisms in milk production traits in dairy cattle. Described comparison of different criteria for determination of significant principal components can provide important information for similar studies in stratified populations., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: In a previous study in the Fleckvieh dual purpose cattle breed, we mapped a quantitative trait locus (QTL) affecting milk yield (MY1), milk protein yield (PY1) and milk fat yield (FY1) during first lactation to the distal part of bovine chromosome 5 (BTA5), but the confidence interval was too large for positional cloning of the causal gene. Our objective here was to refine the position of this QTL and to define the candidate region for high-throughput sequencing., Methods: In addition to those previously studied, new Fleckvieh families were genotyped, in order to increase the number of recombination events. Twelve new microsatellites and 240 SNP markers covering the most likely QTL region on BTA5 were analysed. Based on haplotype analysis performed in this complex pedigree, families segregating for the low frequency allele of this QTL (minor allele) were selected. Single- and multiple-QTL analyses using combined linkage and linkage disequilibrium methods were performed., Results: Single nucleotide polymorphism haplotype analyses on representative family sires and their ancestors revealed that the haplotype carrying the minor QTL allele is rare and most probably originates from a unique ancestor in the mapping population. Analyses of different subsets of families, created according to the results of haplotype analysis and availability of SNP and microsatellite data, refined the previously detected QTL affecting MY1 and PY1 to a region ranging from 117.962 Mb to 119.018 Mb (1.056 Mb) on BTA5. However, the possibility of a second QTL affecting only PY1 at 122.115 Mb was not ruled out., Conclusion: This study demonstrates that targeting families segregating for a less frequent QTL allele is a useful method. It improves the mapping resolution of the QTL, which is due to the division of the mapping population based on the results of the haplotype analysis and to the increased frequency of the minor allele in the families. Consequently, we succeeded in refining the region containing the previously detected QTL to 1 Mb on BTA5. This candidate region contains 27 genes with unknown or partially known function(s) and is small enough for high-throughput sequencing, which will allow future detailed analyses of candidate genes.

It is widely accepted that autochthonous cattle breeds can be important genetic resources for unforeseeable environmental conditions in the future. Apart from that, they often represent local culture and tradition and thus assist in the awareness of ethnic identity of a country. In Croatia, there are only three indigenous cattle breeds, Croatian Buša, Slavonian Syrmian Podolian and Istrian Cattle. All of them are threatened but specialized in a particular habitat and production system. We analysed 93 microsatellites in 51 animals of each breed to get thorough information about genetic diversity and population structure. We further set them within an existing frame of additional 16 breeds that have been genotyped for the same marker set and cover a geographical area from the domestication centre near Anatolia, through the Balkan and alpine regions, to the north-west of Europe. The cultural value was evaluated regarding the role in landscape, gastronomy, folklore and handicraft. The overall results recognize Croatian Buša being partly admixed but harbouring an enormous genetic diversity comparable with other traditional unselected Buša breeds in the Anatolian and Balkan areas. The Podolian cattle showed the lowest genetic diversity at the highest genetic distance to all remaining breeds but are playing an important role as part of the cultural landscape and thus contribute to the tourist industry. The genetic diversity of the Istrian cattle was found in the middle range of this study. It is already included in the tourist industry as a local food speciality. Current and future conservation strategies are discussed., (© 2010 Blackwell Verlag GmbH.)

We analysed a QTL affecting milk yield (MY), milk protein yield (PY) and milk fat yield (FY) in the dual purpose cattle breed Fleckvieh on BTA5. Twenty-six microsatellite markers covering 135 cM were selected to analyse nine half-sib families containing 605 sons in a granddaughter design. We thereby assigned two new markers to the public linkage map using the CRI-MAP program. Phenotypic records were daughter yield deviations (DYD) originating from the routinely performed genetic evaluations of breeding animals. To determine the position of the QTL, three different approaches were applied: interval mapping (IM), linkage analysis by variance component analysis (LAVC), and combined linkage disequilibrium (LD) and linkage (LDL) analysis. All three methods mapped the QTL in the same marker interval (BM2830-ETH152) with the greatest test-statistic value at 118, 119.33 and 119.33 cM respectively. The positive QTL allele simultaneously increases DYD in the first lactation by 272 kg milk, 7.1 kg milk protein and 7.0 kg milk fat. Although the mapping accuracy and the significance of a QTL effect increased from IM over LAVC to LDL, the confidence interval was large (13, 20 and 24 cM for FY, MY and PY respectively) for the positional cloning of the causal gene. The estimated averages of pair wise marker LD with a distance <5 cM were low (0.107) and reflect the large effective population size of the Fleckvieh subpopulation analysed. This low level of LD suggests a need for increase in marker density in following fine mapping steps.

In times of rapid global and unforeseeable environmental changes, there is an urgent need for a sustainable cattle breeding policy, based on a global view. Most of the indigenous breeds are specialized in a particular habitat or production system but are rapidly disappearing. Thus, they represent an important resource to meet present and future breeding objectives. Based on 105 microsatellites, we obtained thorough information on genetic diversity and population structure of 16 cattle breeds that cover a geographical area from the domestication centre near Anatolia, through the Balkan and alpine regions, to the North-West of Europe. Breeds under strict artificial selection and indigenous breeds under traditional breeding schemes were included. The overall results showed that the genetic diversity is widespread in Busa breeds in the Anatolian and Balkan areas, when compared with the alpine and north-western European breeds. Our results reflect long-term evolutionary and short-term breeding events very well. The regular pattern of allele frequency distribution in the entire cattle population studied clearly suggests conservation of rare alleles by conservation of preferably unselected traditional breeds with large effective population sizes. From a global and long-term conservation genetics point of view, the native and highly variable breeds closer to the domestication centre could serve as valuable sources of genes for future needs, not only for cattle but also for other farm animals.

A whole genome scan to map quantitative trait loci (QTL) for persistency of milk yield (PMY), persistency of fat yield (PFY), persistency of protein yield (PPY) and persistency of milk energy yield (PEY) was performed in a granddaughter design in the German Holstein dairy cattle population. The analysis included 16 paternal half-sib families with a total of 872 bulls. The analysis was carried out for the first lactation and for the first three lactations combined using univariate weighted multimarker regression. Controlling the false discovery rate across traits and data sets at a level of 0.15 and treating the four persistency traits as different traits revealed 27 significant QTL. A total of 12 chromosomes showed significant QTL effects on a chromosomewise basis. The DGAT1 effect was highly significant for PPY and protein yield. A haplotype analysis using results of previous studies of the same design revealed a co-segregation of various persistency QTL and QTL affecting health traits like dystocia and stillbirth and functional traits like non-return rate 90 and somatic cell score.

Genome scans for quantitative trait loci (QTL) in farm animals have concentrated on primary production and health traits, and information on QTL for other important traits is rare. We performed a whole genome scan in a granddaughter design to detect QTL affecting body conformation and behavior in dairy cattle. The analysis included 16 paternal half-sib families of the Holstein breed with 872 sons and 264 genetic markers. The markers were distributed across all 29 autosomes and the pseudoautosomal region of the sex chromosomes with average intervals of 13.9 cM and covering an estimated 3155.5 cM. All families were analyzed jointly for 22 traits using multimarker regression and significance thresholds determined empirically by permutation. QTL that exceeded the experiment-wise significance threshold (5% level) were detected on chromosome 6 for foot angle, teat placement, and udder depth, and on chromosome 29 for temperament. QTL approaching experiment-wise significance (10% level) were located on chromosome 6 for general quality of feet and legs and general quality of udder, on chromosome 13 for teat length, on chromosome 23 for general quality of feet and legs, and on chromosome 29 for milking speed. An additional 51 QTL significant at the 5% chromosome-wise level were distributed over 21 chromosomes. This study provides the first evidence for QTL involved in behavior of dairy cattle and identifies QTL for udder conformation on chromosome 6 that could form the basis of recently reported QTL for clinical mastitis.

A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89-94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.

A joint analysis of five paternal half-sib Holstein families that were part of two different granddaughter designs (ADR- or Inra-design) was carried out for five milk production traits and somatic cell score in order to conduct a QTL confirmation study and to increase the experimental power. Data were exchanged in a coded and standardised form. The combined data set (JOINT-design) consisted of on average 231 sires per grandsire. Genetic maps were calculated for 133 markers distributed over nine chromosomes. QTL analyses were performed separately for each design and each trait. The results revealed QTL for milk production on chromosome 14, for milk yield on chromosome 5, and for fat content on chromosome 19 in both the ADR- and the Inra-design (confirmed within this study). Some QTL could only be mapped in either the ADR- or in the Inra-design (not confirmed within this study). Additional QTL previously undetected in the single designs were mapped in the JOINT-design for fat yield (chromosome 19 and 26), protein yield (chromosome 26), protein content (chromosome 5), and somatic cell score (chromosome 2 and 19) with genomewide significance. This study demonstrated the potential benefits of a combined analysis of data from different granddaughter designs.

A whole-genome scan to detect quantitative trait loci (QTL) for functional traits was performed in the German Holstein cattle population. For this purpose, 263 genetic markers across all autosomes and the pseudoautosomal region of the sex chromosomes were genotyped in 16 granddaughter-design families with 872 sons. The traits investigated were deregressed breedingvalues for maternal and direct effects on dystocia (DYSm, DYSd) and stillbirth (STIm, STId) as well as maternal and paternal effects on nonreturn rates of 90 d (NR90m, NR90p). Furthermore, deregressed breeding values for functional herd life (FHL) and daughter yield deviation for somatic cell count (SCC) were investigated. Weighted multimarker regression analyses across families and permutation tests were applied for the detection of QTL and the calculation of statistical significance. A ten percent genomewise significant QTL was localized for DYSm on chromosome 8 and for SCC on chromosome 18. A further 24 putative QTL exceeding the 5% chromosomewise threshold were detected. On chromosomes 7, 8, 10, 18, and X/Yps, coincidence of QTL for several traits was observed. Our results suggest that loci with influence on udder health may also contribute to genetic variance of longevity. Prior to implementation of these QTL in marker assisted selection programs for functional traits, information about direct and correlated effects of these QTL as well as fine mapping of their chromosomal positions is required.

Genes determining the bovine erythrocyte antigens were mapped by linkage analysis. In total 9591 genotypes of 20 grandsire families with 1074 sires from a grand-daughter design were elucidated for the genes determining the erythrocyte antigens EAA, EAB, EAC, EAF, EAJ, EAL, EAM, EAN', EAR', EAS, EAT', and EAZ according to standard paternity testing procedures in the blood typing laboratories. Linkage analyses were performed with 248 microsatellite markers, eight SSCP markers and four polymorphic proteins and enzymes covering the 29 autosomes and the pseudoautosomal region of the sex chromosomes. The number of informative meioses for the blood group systems ranged from 76 to 947. Blood group systems EAM and EAT' were non-informative. Most of the erythrocyte antigen loci showed significant linkage to a single chromosome and were mapped unequivocally. The genes determining erythrocyte antigen EAA, EAB, EAC, EAL, and EAS were mapped to chromosomes 15, 12, 18, 3, and 21, respectively. Lod-score values ranged from 11.43 to 107.83. Moreover, the EAF system could be mapped to chromosome 17. However, the EAN' system previously known as part of the EAF system could be mapped to chromosome 5. In addition, the blood group systems EAJ, the new EAN', EAR', and EAZ, showed significant linkage to microsatellite markers on various chromosomes and also to other blood groups. The appearance of a single blood group system might be therefore either dependent on the existence of other blood group systems or because of an interaction between different loci on various chromosomes as is known in humans and in pigs.

Twenty paternal half-sib families of a granddaughter design were genotyped for 265 genetic markers, most of them microsatellites. These were 16 Holstein families, 3 Simmental families, and 1 Brown Swiss family. The number of sires per breed was 872, 170, and 32, respectively. Two-point recombination rates were estimated both jointly for all breeds and each single breed separately. Of 1168 marker intervals, 865 provided estimates for at least two breeds. Differences between breeds were tested by likelihood ratio tests. Four marker intervals, representing three genomic regions on BTA19, BTA24, and BTA27, show a significant impact of the breed at a false discovery rate of 0.23 and indicate a genetic component of observed heterogeneity of recombination. The variability of recombination rates between cattle breeds might not be a common feature of the whole genome, but rather might be restricted to certain chromosomal segments. Thus, attention should be paid to heterogeneities when pooling data of such regions from different breeds.

The complete cDNA sequence of a ribonuclease k6 gene of Bos Taurus has been determined. It codes for a protein with 154 amino acids and contains the invariant cysteine, histidine and lysine residues as well as the characteristic motifs specific to ribonuclease active sites. The deduced protein sequence is 27 residues longer than other known ribonucleases k6 and shows amino acids exchanges which could reflect a strain specificity or polymorphism within the bovine genome. Based on sequence similarity we have termed the identified gene bovine ribonuclease k6 b (brk6b).

The proportion of unpigmented coat on the trunk was determined from photographs of 38 German Simmental and 627 German Holstein bulls distributed over three generations. All 665 animals were members of 18 Holstein and 3 Simmental half-sib families. A Bayesian estimation of heritability yielded a posterior mean of 0.88 and a standard error of 0.08. A quantitative trait loci (QTL) scan over all chromosomes covered by 229 microsatellite marker loci (2926 cM) was performed by fitting a multiple marker regression model to 625 observations from the youngest generation in 18 families. On chromosome 6 a QTL for the proportion of white coat with large effects (experiment-wise error probability < .0001) was found and a less important one on chromosome 3 (chromosome-wise error probability < .009). Chromosome 6 is known to harbor the KIT locus (receptor tyrosinase kinase), which is associated with various depigmentation phenotypes in mice, humans, and pigs. Similarity of phenotypic KIT effects in other species and synteny with the reported QTL suggest that KIT is a serious candidate gene for the degree of spotting in cattle. The results are also discussed with respect to resistance to solar radiation, heat stress, and photosensitization.

Different autosomal chromosome fusions at piebald cattle and brown cattle are described. In randomly investigated breeds of cattle in Germany, we found 1/25 translocation in piebald cattle and a 1/29 Robertsonian fusion in brown cattle. Fertility differences were investigated.

Naturally, hornless cattle are called polled. Although the POLL locus could be assigned to a c. 1.36-Mb interval in the centromeric region of BTA1, the underlying genetic basis for the polled trait is still unknown. Here, an association mapping design was set up to refine the candidate region of the polled trait for subsequent high-throughput sequencing. The case group comprised 101 homozygous polled animals from nine divergent cattle breeds, the majority represented by Galloway, Angus, Fleckvieh and Holstein Friesian. Additionally, this group included some polled individuals of Blonde d' Aquitaine, Charolais, Hereford, Jersey and Limousin breeds. The control group comprised horned Belgian Blue, Fleckvieh, Holstein Friesian and Illyrian Buša cattle. A genome-wide scan using 49 163 SNPs was performed, which revealed one shared homozygous haplotype block consisting of nine neighbouring SNPs in all polled animals. This segment defines a 381-kb interval on BTA1 that we consider to be the most likely location of the POLL mutation. Our results further demonstrate that the polled-associated haplotype is also frequent in horned animals included in this study, and thus the haplotype as such cannot be used for population-wide genetic testing. The actual trait-associated haplotype may be revealed by using higher-density SNP arrays. For the final identification of the causal mutation, we suggest high-throughput sequencing of the entire candidate region, because the identification of functional candidate genes is difficult owing to the lack of a comparable model. [ABSTRACT FROM AUTHOR]