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Ivica Medugorac - One of the best experts on this subject based on the ideXlab platform.
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detection of two non synonymous snps in slc45a2 on bta20 as candidate causal mutations for oculocutaneous albinism in Braunvieh Cattle
Genetics Selection Evolution, 2017Co-Authors: Sophie Rothamme, Martina Wassertheure, Ruedi Fries, Doris Seichte, Elisabeth Kunz, Stefa Krebs, Ivica MedugoracAbstract:Cases of albinism have been reported in several species including Cattle. So far, research has identified many genes that are involved in this eye-catching phenotype. Thus, when two paternal Braunvieh half-sibs with oculocutaneous albinism were detected on a private farm, we were interested in knowing whether their phenotype was caused by an already known gene/mutation. Analysis of genotyping data (50K) of the two albino individuals, their mothers and five other relatives identified a 47.61-Mb candidate haplotype on Bos taurus chromosome BTA20. Subsequent comparisons of the sequence of this haplotype with sequence data from four Braunvieh sires and the Aurochs genome identified two possible candidate causal mutations at positions 39,829,806 bp (G/A; R45Q) and 39,864,148 bp (C/T; T444I) that were absent in 1682 animals from various bovine breeds included in the 1000 bull genomes project. Both polymorphisms represent coding variants in the SLC45A2 gene, for which the human equivalent harbors numerous variants associated with oculocutaneous albinism type 4. We demonstrate an association of R45Q and T444I with the albino phenotype by targeted genotyping. Although the candidate gene SLC45A2 is known to be involved in albinism in different species, to date in Cattle only mutations in the TYR and MITF genes were reported to be associated with albinism or albinism-like phenotypes. Thus, our study extends the list of genes that are associated with bovine albinism. However, further research and more samples from related animals are needed to elucidate if only one of these two single nucleotide polymorphisms or the combination of both is the actual causal variant.
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Detection of two non-synonymous SNPs in SLC45A2 on BTA20 as candidate causal mutations for oculocutaneous albinism in Braunvieh Cattle
Genetics Selection Evolution, 2017Co-Authors: Sophie Rothammer, Gottfried Brem, Doris Seichter, Stefan Krebs, Martina Wassertheurer, Ruedi Fries, Elisabeth Kunz, Ivica MedugoracAbstract:Background Cases of albinism have been reported in several species including Cattle. So far, research has identified many genes that are involved in this eye-catching phenotype. Thus, when two paternal Braunvieh half-sibs with oculocutaneous albinism were detected on a private farm, we were interested in knowing whether their phenotype was caused by an already known gene/mutation. Results Analysis of genotyping data (50K) of the two albino individuals, their mothers and five other relatives identified a 47.61-Mb candidate haplotype on Bos taurus chromosome BTA20. Subsequent comparisons of the sequence of this haplotype with sequence data from four Braunvieh sires and the Aurochs genome identified two possible candidate causal mutations at positions 39,829,806 bp (G/A; R45Q) and 39,864,148 bp (C/T; T444I) that were absent in 1682 animals from various bovine breeds included in the 1000 bull genomes project. Both polymorphisms represent coding variants in the SLC45A2 gene, for which the human equivalent harbors numerous variants associated with oculocutaneous albinism type 4. We demonstrate an association of R45Q and T444I with the albino phenotype by targeted genotyping. Conclusions Although the candidate gene SLC45A2 is known to be involved in albinism in different species, to date in Cattle only mutations in the TYR and MITF genes were reported to be associated with albinism or albinism-like phenotypes. Thus, our study extends the list of genes that are associated with bovine albinism. However, further research and more samples from related animals are needed to elucidate if only one of these two single nucleotide polymorphisms or the combination of both is the actual causal variant.
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genome wide association mapping of milk production traits in Braunvieh Cattle
Journal of Dairy Science, 2012Co-Authors: Jiří Maxa, Markus Neuditschko, Ingolf Russ, M Forste, Ivica MedugoracAbstract: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.
Marek Doležal - One of the best experts on this subject based on the ideXlab platform.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
BMC Genomics, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh Cattle resulting in a depletion of BH2 homozygous adult animals (P = 9.3x10−12). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P = 2.2x10−15). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh Cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh Cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh Cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed Cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
BMC Genomics, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Background Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
bioRxiv, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Background: Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. Results: The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh Cattle resulting in a depletion of BH2 homozygous adult animals (P=9.3x10-12). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P=2.2x10-15). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh Cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. Conclusions: A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh Cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh Cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed Cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
H Schwarzenbache - One of the best experts on this subject based on the ideXlab platform.
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exploring the potential genetic heterogeneity in the incidence of hoof and leg disorders in austrian fleckvieh and Braunvieh Cattle
bioRxiv, 2020Co-Authors: Arbara Kosinskaselbi, Tomasz Suchocki, Christa Eggerdanne, Magdalena Fraszczak, Joanna Szyda, H SchwarzenbacheAbstract:Background: Genetic heterogeneity denotes the situation when different genetic architectures underlying diverse populations result in the same phenotype. In this study, we explore the nature of differences in the incidence of the number of hoof and leg disorders between Braunvieh and Fleckvieh Cattle in the context of genetic heterogeneity between the breeds. Results: Despite potentially higher power of testing due to twice as large sample size, none of the SNPs was significantly associated with the number of hoof and leg disorders in Fleckvieh, while 16 SNPs were significant in Braunvieh. The most promising candidate genes in Braunvieh are: CBLB on BTA01, which causes arthritis in rats; CAV2 on BTA04, which in effects mouse skeletal muscles; PTHLH on BTA05, which causes disease phenotypes related to the skeleton in humans, mice and zebrafish; SORCS2 on BTA06, which causes decreased susceptibility to injury in the mouse. Some of the significant SNPs (BTA01, BTA04, BTA05, BTA13, BTA16) reveal allelic heterogeneity: i.e. differences due to different allele frequencies between Fleckvieh and Braunvieh. Some of the significant regions (BTA01, BTA05, BTA13, BTA16) correlate to inter breed differences in LD structure and may thus represent false positive heterogeneity. However, positions on BTA06 (SORCS2), BTA14 and BTA24 mark Braunvieh specific regions. Conclusions: We hypothesise that the observed genetic heterogeneity of hoof and leg disorders is a by product of multigenerational differential selection of the breeds towards dairy production in the case of Braunvieh and towards beef production in the case of Fleckvieh. Based on the current data set it is no possibly to unequivocally confirm/exclude the hypothesis of genetic heterogeneity in the susceptibility to leg disorders between Fleckvieh and Braunvieh because only explore it through associations and not the causal mutations. Rationales against genetic heterogeneity comprise a limited power of detection of true associations as well as differences in the length of LD blocks and in linkage phase between breeds. On the other hand, multigenerational differential selection of the breeds and no systematic differences in LD structure between the breeds favour the heterogeneity hypothesis at some of the significant sites. Keywords: Braunvieh, feet and leg disorders, Fleckvieh, genetic heterogeneity, GWAS, linkage disequilibrium, principal components
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
BMC Genomics, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Background Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
BMC Genomics, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh Cattle resulting in a depletion of BH2 homozygous adult animals (P = 9.3x10−12). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P = 2.2x10−15). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh Cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh Cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh Cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed Cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
bioRxiv, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Background: Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. Results: The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh Cattle resulting in a depletion of BH2 homozygous adult animals (P=9.3x10-12). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P=2.2x10-15). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh Cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. Conclusions: A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh Cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh Cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed Cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
Joanna Szyda - One of the best experts on this subject based on the ideXlab platform.
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exploring the potential genetic heterogeneity in the incidence of hoof disorders in austrian fleckvieh and Braunvieh Cattle
Frontiers in Genetics, 2020Co-Authors: Barbara Kosinskaselbi, Tomasz Suchocki, Christa Eggerdanner, Hermann Schwarzenbacher, Magdalena Frąszczak, Joanna SzydaAbstract:Genetic heterogeneity denotes the situation when different genetic architectures underlying diverse populations result in the same phenotype. In this study, we explore the genetic background underlying differences in the incidence of hoof disorders between Braunvieh and Fleckvieh Cattle in the context of genetic heterogeneity between the breeds. Despite potentially higher power of testing due to twice as large sample size, none of the SNPs was significantly associated with the total number of hoof disorders in Fleckvieh, while 15 SNPs were significant in Braunvieh. The most promising candidate genes in Braunvieh were as follows: CBLB on BTA1, which causes arthritis in rats; CAV2 on BTA4, which affects skeletal muscles in mice; PTHLH on BTA5, which causes disease phenotypes related to the skeleton in humans, mice, and zebrafish; and SORCS2 on BTA6, which causes decreased susceptibility to injury in mice. Some of the significant SNPs (BTA1, BTA4, BTA5, BTA13, and BTA16) revealed allelic heterogeneity-i.e., different allele frequencies between Fleckvieh and Braunvieh. Some of the significant regions (BTA1, BTA5, BTA13, and BTA16) correlated to inter-breed differences in linkage disequilibrium (LD) structure and may thus represent false-positive heterogeneity. However, positions on BTA6 (SORCS2), BTA14, and BTA24 mark Braunvieh-specific regions. We hypothesize that the observed genetic heterogeneity of hoof disorders is a by-product of different selection goals defined for the analyzed breeds-toward dairy production in Braunvieh and toward beef production in Fleckvieh. Based on the current dataset, it is not possible to unequivocally confirm or exclude the hypothesis of genetic heterogeneity in the susceptibility to hoof disorders between Fleckvieh and Braunvieh. The main reason for the problem is that the potential heterogeneity was explored through SNP-phenotype associations and not through causal mutations, due to a limited SNP density offered by the SNP-chip. The rationale against genetic heterogeneity comprises a limited power of detection of true associations as well as differences in the length of LD blocks and in linkage phase between breeds. On the other hand, different selection goals defined for the analyzed breeds accompanied by no systematic, genome-wide differences in LD structure between the breeds favor the heterogeneity hypothesis at some smaller genomic regions.
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exploring the potential genetic heterogeneity in the incidence of hoof and leg disorders in austrian fleckvieh and Braunvieh Cattle
bioRxiv, 2020Co-Authors: Arbara Kosinskaselbi, Tomasz Suchocki, Christa Eggerdanne, Magdalena Fraszczak, Joanna Szyda, H SchwarzenbacheAbstract:Background: Genetic heterogeneity denotes the situation when different genetic architectures underlying diverse populations result in the same phenotype. In this study, we explore the nature of differences in the incidence of the number of hoof and leg disorders between Braunvieh and Fleckvieh Cattle in the context of genetic heterogeneity between the breeds. Results: Despite potentially higher power of testing due to twice as large sample size, none of the SNPs was significantly associated with the number of hoof and leg disorders in Fleckvieh, while 16 SNPs were significant in Braunvieh. The most promising candidate genes in Braunvieh are: CBLB on BTA01, which causes arthritis in rats; CAV2 on BTA04, which in effects mouse skeletal muscles; PTHLH on BTA05, which causes disease phenotypes related to the skeleton in humans, mice and zebrafish; SORCS2 on BTA06, which causes decreased susceptibility to injury in the mouse. Some of the significant SNPs (BTA01, BTA04, BTA05, BTA13, BTA16) reveal allelic heterogeneity: i.e. differences due to different allele frequencies between Fleckvieh and Braunvieh. Some of the significant regions (BTA01, BTA05, BTA13, BTA16) correlate to inter breed differences in LD structure and may thus represent false positive heterogeneity. However, positions on BTA06 (SORCS2), BTA14 and BTA24 mark Braunvieh specific regions. Conclusions: We hypothesise that the observed genetic heterogeneity of hoof and leg disorders is a by product of multigenerational differential selection of the breeds towards dairy production in the case of Braunvieh and towards beef production in the case of Fleckvieh. Based on the current data set it is no possibly to unequivocally confirm/exclude the hypothesis of genetic heterogeneity in the susceptibility to leg disorders between Fleckvieh and Braunvieh because only explore it through associations and not the causal mutations. Rationales against genetic heterogeneity comprise a limited power of detection of true associations as well as differences in the length of LD blocks and in linkage phase between breeds. On the other hand, multigenerational differential selection of the breeds and no systematic differences in LD structure between the breeds favour the heterogeneity hypothesis at some of the significant sites. Keywords: Braunvieh, feet and leg disorders, Fleckvieh, genetic heterogeneity, GWAS, linkage disequilibrium, principal components
F Seefried - One of the best experts on this subject based on the ideXlab platform.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
BMC Genomics, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh Cattle resulting in a depletion of BH2 homozygous adult animals (P = 9.3x10−12). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P = 2.2x10−15). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh Cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh Cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh Cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed Cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
BMC Genomics, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Background Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated.
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a missense mutation in tubd1 is associated with high juvenile mortality in Braunvieh and fleckvieh Cattle
bioRxiv, 2016Co-Authors: H Schwarzenbache, Joha Urgstalle, F Seefried, Christine Wurmse, Monika Hilbe, Simone Jung, Nora Dinhopl, Herbe Weissenbock, C Fuers, Marek DoležalAbstract:Background: Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh Cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. Results: The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh Cattle resulting in a depletion of BH2 homozygous adult animals (P=9.3x10-12). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P=2.2x10-15). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh Cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. Conclusions: A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh Cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh Cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed Cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
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Accuracy of 54K to HD gebotype imputation in Brown Swiss Cattle
2013Co-Authors: B. Gredler, Malihe Sargolzaei, Beat Bapst, Anna Bieber, Henner Simianer, F SeefriedAbstract:Imputation of genotypes can be used to reduce the implementation costs of genomic selection. In this study, we evaluated the accuracy of genotype imputation from Illumina 54k to Illumina High Density (HD) in Brown Swiss Cattle. Genotype data comprised 6,106 54k and 880 HD genotyped bulls and cows of Brown Swiss and Original Braunvieh Cattle. Genotype data was checked for parentage conflicts and SNP were excluded if MAF was below 0.5% and SNP call rate was lower than 90%. The final data set included 39,004 SNP for the 54k and 627,306 SNP for the HD chip. HD genotypes of animals born between 2004 and 2008 (n=365) were masked to mimic animals genotyped with the 54k chip. Methods used for imputation were FImpute and Findhap V2. Both programs use pedigree information for imputation. The accuracy of imputation was assessed by the correlation (r) between true and imputed genotypes, the percentage of correctly and incorrectly imputed genotypes. Both programs gave high imputation accuracy with FImpute outperforming Findhap. Accuracy of imputation increased with increasing relationship between the HD genotyped reference population and 54k genotyped imputation candidates. Average r for FImpute and Findhap were 0.992 and 0.988 when both parents of the 54k genotyped candidate were HD genotyped, respectively. Correlations were lower when no direct relatives were HD genotyped (0.971 and 0.918 for FImpute and Findhap, respectively). Accuracy of imputation highly depended on MAF of the imputed SNP. For FImpute, average r ranged between 0.89 (MAF