Publications (25)83.61 Total impact
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Article: Imputation of high-density genotypes in the Fleckvieh cattle population.
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ABSTRACT: BACKGROUND: Currently, genome-wide evaluation of cattle populations is based on SNP-genotyping using ~ 54 000 SNP. Increasing the number of markers might improve genomic predictions and power of genome-wide association studies. Imputation of genotypes makes it possible to extrapolate genotypes from lower to higher density arrays based on a representative reference sample for which genotypes are obtained at higher density. METHODS: Genotypes using 639 214 SNP were available for 797 bulls of the Fleckvieh cattle breed. The data set was divided into a reference and a validation population. Genotypes for all SNP except those included in the BovineSNP50 Bead chip were masked and subsequently imputed for animals of the validation population. Imputation of genotypes was performed with Beagle, findhap.f90, MaCH and Minimac. The accuracy of the imputed genotypes was assessed for four different scenarios including 50, 100, 200 and 400 animals as reference population. The reference animals were selected to account for 78.03%, 89.21%, 97.47% and > 99% of the gene pool of the genotyped population, respectively. RESULTS: Imputation accuracy increased as the number of animals and relatives in the reference population increased. Population-based algorithms provided highly reliable imputation of genotypes, even for scenarios with 50 and 100 reference animals only. Using MaCH and Minimac, the correlation between true and imputed genotypes was > 0.975 with 100 reference animals only. Pre-phasing the genotypes of both the reference and validation populations not only provided highly accurate imputed genotypes but was also computationally efficient. Genome-wide analysis of imputation accuracy led to the identification of many misplaced SNP. CONCLUSIONS: Genotyping key animals at high density and subsequent population-based genotype imputation yield high imputation accuracy. Pre-phasing the genotypes of the reference and validation populations is computationally efficient and results in high imputation accuracy, even when the reference population is small.Genetics Selection Evolution 02/2013; 45(1):3. · 2.88 Impact Factor -
Article: Cytogenetic mapping ofDGAT1, PPARA, ADIPOR1 andCREB genes in the pig
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ABSTRACT: In the present study we show FISH localization of 4 porcine BAC clones harbouring potential candidate genes for fatness traits:DGAT1 (SSC4p15),PPARA (SSC5p15),ADIPOR1 (SSC10p13) andCREB (SSC15q24). Until now theCREB andADIPOR1 genes are considered to be monomorphic,DGAT1 is highly polymorphic, while for thePPARA gene only 1 SNP was identified. Assignment of the studied genes in relation to QTL chromosome regions for meat quality in pig chromosomes SSC4, SSC5, SSC10 and SSC15 is discussed. Keywordspig-lipid metabolism-fatness traits-FISH-DGAT1-PPARA-ADIPOR1-CREBJournal of applied genetics 04/2012; 48(1):73-76. · 1.66 Impact Factor -
Article: Genome-wide association study uncovers four QTL predisposing to supernumerary teats in cattle.
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ABSTRACT: Supernumerary teats (hyperthelia, SNTs) are a common abnormality of the bovine udder with a medium to high heritability and a postulated oligogenic or polygenic inheritance pattern. SNTs not only negatively affect machine milking ability but also act as a reservoir for bacteria. A genome-wide association study was carried out to identify genes involved in the development of SNTs in the dual-purpose Fleckvieh breed. A total of 2467 progeny-tested bulls were genotyped at 43 698 single nucleotide polymorphisms, and daughter yield deviations (DYDs) for 'udder clearness' (UC) were used as high-heritability phenotypes. Massive structuring of the study population was accounted for by principal components analysis-based and mixed model-based approaches. Four loci on BTA5, BTA6, BTA11 and BTA17 were significantly associated with the UC DYD. Three associated regions contain genes of the highly conserved Wnt signalling pathway. The four QTL together account for 10.7% of the variance of the UC DYD, whereas the major fraction of the DYD variance is attributable to chromosomes with no identified QTL. Our results support both an oligogenic and a polygenic inheritance pattern of SNTs in cattle. The identified candidate genes permit insights into the genetic architecture of teat malformations in cattle and provide clues to unravel the molecular mechanisms of mammary gland alterations in cattle and other species.Animal Genetics 03/2012; 43(6):689-95. · 2.40 Impact Factor -
Article: Combining evidence of selection with association analysis increases power to detect regions influencing complex traits in dairy cattle.
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ABSTRACT: Hitchhiking mapping and association studies are two popular approaches to map genotypes to phenotypes. In this study we combine both approaches to complement their specific strengths and weaknesses, resulting in a method with higher statistical power and fewer false positive signals. We applied our approach to dairy cattle as they underwent extremely successful selection for milk production traits and since an excellent phenotypic record is available. We performed whole genome association tests with a new mixed model approach to account for stratification, which we validated via Monte Carlo simulations. Selection signatures were inferred with the integrated haplotype score and a locus specific permutation based integrated haplotype score that works with a folded frequency spectrum and provides a formal test of signifance to identify selection signatures. About 1,600 out of 34,851 SNPs showed signatures of selection and the locus specific permutation based integrated haplotype score showed overall good accordance with the whole genome association study. Each approach provides distinct information about the genomic regions that influence complex traits. Combining whole genome association with hitchhiking mapping yielded two significant loci for the trait protein yield. These regions agree well with previous results from other selection signature scans and whole genome association studies in cattle. We show that the combination of whole genome association and selection signature mapping based on the same SNPs increases the power to detect loci influencing complex traits. The locus specific permutation based integrated haplotype score provides a formal test of significance in selection signature mapping. Importantly it does not rely on knowledge of ancestral and derived allele states.BMC Genomics 01/2012; 13:48. · 4.07 Impact Factor -
Article: Identification and dissection of four major QTL affecting milk fat content in the German Holstein-Friesian population.
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ABSTRACT: Milk composition traits exhibit a complex genetic architecture with a small number of major quantitative trait loci (QTL) explaining a large fraction of the genetic variation and numerous QTL with minor effects. In order to identify QTL for milk fat percentage (FP) in the German Holstein-Friesian (HF) population, a genome-wide association study (GWAS) was performed. The study population consisted of 2327 progeny-tested bulls. Genotypes were available for 44,280 SNPs. Phenotypes in the form of estimated breeding values (EBVs) for FP were used as highly heritable traits. A variance components-based approach was used to account for population stratification. The GWAS identified four major QTL regions explaining 46.18% of the FP EBV variance. Besides two previously known FP QTL on BTA14 (P = 8.91×10-(198)) and BTA20 (P = 7.03×10(-12)) within DGAT1 and GHR, respectively, we uncovered two additional QTL regions on BTA5 (P = 2.00×10(-13)) and BTA27 (P = 9.83×10(-5)) encompassing EPS8 and GPAT4, respectively. EPS8 and GPAT4 are involved in lipid metabolism in mammals. Re-sequencing of EPS8 and GPAT4 revealed 50 polymorphisms. Genotypes for five of them were inferred for the entire study population. Two polymorphisms affecting potential transcription factor binding sites of EPS8 (P = 1.40×10(-12)) and GPAT4 (P = 5.18×10(-5)), respectively, were highly significantly associated with the FP EBV. Our results provide evidence that alteration of regulatory sites is an important aspect of genetic variation of complex traits in cattle.PLoS ONE 01/2012; 7(7):e40711. · 4.09 Impact Factor -
Article: Identification of QTL for UV-protective eye area pigmentation in cattle by progeny phenotyping and genome-wide association analysis.
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ABSTRACT: Pigmentation patterns allow for the differentiation of cattle breeds. A dominantly inherited white head is characteristic for animals of the Fleckvieh (FV) breed. However, a minority of the FV animals exhibits peculiar pigmentation surrounding the eyes (ambilateral circumocular pigmentation, ACOP). In areas where animals are exposed to increased solar ultraviolet radiation, ACOP is associated with a reduced susceptibility to bovine ocular squamous cell carcinoma (BOSCC, eye cancer). Eye cancer is the most prevalent malignant tumour affecting cattle. Selection for animals with ACOP rapidly reduces the incidence of BOSCC. To identify quantitative trait loci (QTL) underlying ACOP, we performed a genome-wide association study using 658,385 single nucleotide polymorphisms (SNPs). The study population consisted of 3579 bulls of the FV breed with a total of 320,186 progeny with phenotypes for ACOP. The proportion of progeny with ACOP was used as a quantitative trait with high heritability (h(2) = 0.79). A variance component based approach to account for population stratification uncovered twelve QTL regions on seven chromosomes. The identified QTL point to MCM6, PAX3, ERBB3, KITLG, LEF1, DKK2, KIT, CRIM1, ATRN, GSDMC, MITF and NBEAL2 as underlying genes for eye area pigmentation in cattle. The twelve QTL regions explain 44.96% of the phenotypic variance of the proportion of daughters with ACOP. The chromosomes harbouring significantly associated SNPs account for 54.13% of the phenotypic variance, while another 19.51% of the phenotypic variance is attributable to chromosomes without identified QTL. Thus, the missing heritability amounts to 7% only. Our results support a polygenic inheritance pattern of ACOP in cattle and provide the basis for efficient genomic selection of animals that are less susceptible to serious eye diseases.PLoS ONE 01/2012; 7(5):e36346. · 4.09 Impact Factor -
Article: Genome-wide association study identifies two major loci affecting calving ease and growth-related traits in cattle.
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ABSTRACT: Identifying quantitative trait loci (QTL) underlying complex, low-heritability traits is notoriously difficult. Prototypical for such traits, calving ease is an important breeding objective of cattle (Bos taurus)-improving programs. To identify QTL underlying calving ease, we performed a genome-wide association study using estimated breeding values (EBVs) as highly heritable phenotypes for paternal calving ease (pCE) and related traits. The massively structured study population consisted of 1800 bulls of the German Fleckvieh (FV) breed. Two pCE-associated regions on bovine chromosomes (BTA) 14 and 21 (P = 5.72 × 10(-15) and P = 2.27 × 10(-8), respectively) were identified using principal components analysis to correct for population stratification. The two most significantly associated SNPs explain 10% of the EBV variation. Since marker alleles with negative effect on pCE have positive effects on growth-related traits, the QTL may exert their effects on the birthing process through fetal growth traits. The QTL region on BTA14 corresponds to a human chromosome (HSA) region that is associated with growth characteristics. The HSA region corresponding to the BTA21 pCE QTL is maternally imprinted and involved in the Prader-Willi and Angelman syndromes. Resequencing of positional candidate genes on BTA14 revealed a highly significantly (P = 1.96 × 10(-14)) associated polymorphism ablating a polyadenylation signal of the gene encoding ribosomal protein S20 (RPS20). Our study demonstrates the leverage potential of EBVs in unraveling the genetic architecture of lowly heritable traits.Genetics 11/2010; 187(1):289-97. · 4.01 Impact Factor -
Article: A novel mutation in the maternally imprinted PEG3 domain results in a loss of MIMT1 expression and causes abortions and stillbirths in cattle (Bos taurus).
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ABSTRACT: Congenital malformations resulting in late abortions and stillbirths affect the economic wellbeing of producers and the welfare of cattle in breeding programs. An extremely high incidence of stillbirths of "half-sized" calves of normal karyotype and uninflated lungs was diagnosed in the progeny of the Finnish Ayrshire (Bos taurus) bull--YN51. No other visible anatomical abnormalities were apparent in the stillborn calves. We herein describe the positional identification of a 110 kb microdeletion in the maternally imprinted PEG3 domain that results in a loss of paternal MIMT1 expression and causes late term abortion and stillbirth in cattle. Using the BovineSNP50 BeadChip we performed a genome-wide half-sib linkage analysis that identified a 13.3 Mb associated region on BTA18 containing the maternally imprinted PEG3 domain. Within this cluster we found a 110 kb microdeletion that removes a part of the non-protein coding MER1 repeat containing imprinted transcript 1 gene (MIMT1). To confirm the elimination of gene expression in calves inheriting this deletion, we examined the mRNA levels of the three maternally imprinted genes within the PEG3 domain, in brain and cotyledon tissue collected from eight fetuses sired by the proband. None of the fetuses that inherited the microdeletion expressed MIMT1 in either tissue. The mutation, when inherited from the sire, is semi-lethal for his progeny with an observed mortality rate of 85%. The survival of 15% is presumably due to the incomplete silencing of maternally inherited MIMT1 alleles. We designed a PCR-based assay to confirm the existence of the microdeletion in the MIMT1 region that can be used to assist cattle breeders in preventing the stillbirths.PLoS ONE 01/2010; 5(11):e15116. · 4.09 Impact Factor -
Article: Dissection of genetic factors modulating fetal growth in cattle indicates a substantial role of the non-SMC condensin I complex, subunit G (NCAPG) gene.
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ABSTRACT: The increasing evidence of fetal developmental effects on postnatal life, the still unknown fetal growth mechanisms impairing offspring generated by somatic nuclear transfer techniques, and the impact on stillbirth and dystocia in conventional reproduction have generated increasing attention toward mammalian fetal growth. We identified a highly significant quantitative trait locus (QTL) affecting fetal growth on bovine chromosome 6 in a specific resource population, which was set up by consistent use of embryo transfer and foster mothers and, thus, enabled dissection of fetal-specific genetic components of fetal growth. Merging our data with results from other cattle populations differing in historical and geographical origin and with comparative data from human whole-genome association mapping suggests that a nonsynonymous polymorphism in the non-SMC condensin I complex, subunit G (NCAPG) gene, NCAPG c.1326T>G, is the potential cause of the identified QTL resulting in divergent bovine fetal growth. NCAPG gene expression data in fetal placentomes with different NCAPG c.1326T>G genotypes, which are in line with recent results about differential NCAPG expression in placentomes from studies on assisted reproduction techniques, indicate that the NCAPG locus may give valuable information on the specific mechanisms regulating fetal growth in mammals.Genetics 08/2009; 183(3):951-64. · 4.01 Impact Factor -
Article: Cytogenetic mapping of DGAT1, PPARA, ADIPOR1 and CREB genes in the pig.
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ABSTRACT: In the present study we show FISH localization of 4 porcine BAC clones harbouring potential candidate genes for fatness traits: DGAT1 (SSC4p15), PPARA (SSC5p15), ADIPOR1 (SSC10p13) and CREB (SSC15q24). Until now the CREB and ADIPOR1 genes are considered to be monomorphic, DGAT1 is highly polymorphic, while for the PPARA gene only 1 SNP was identified. Assignment of the studied genes in relation to QTL chromosome regions for meat quality in pig chromosomes SSC4, SSC5, SSC10 and SSC15 is discussed.Journal of applied genetics 02/2007; 48(1):73-6. · 1.66 Impact Factor -
Article: Alleles of the bovine DGAT1 variable number of tandem repeat associated with a milk fat QTL at chromosome 14 can stimulate gene expression.
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ABSTRACT: A quantitative trait locus (QTL) affecting milk fat percentage has been mapped to the centromeric end of the bovine chromosome 14 (BTA14). This genomic area includes the DGAT1 gene, which encodes acyl-CoA:diacylglycerol acyltransferase 1, the key enzyme of triglyceride biosynthesis. Genetic and biochemical studies led to the identification of the nonconservative DGAT1-K232A polymorphism as a causal mutation for the QTL. In addition to this, another polymorphism in the 5'-regulatory region of this gene, the DGAT1 variable number of tandem repeat (VNTR), also showed a strong association with milk fat percentage. This promoter VNTR polymorphism affects the number of potential Sp1 binding sites and therefore might have an impact on DGAT1 expression and also milk fat content. Hence, the DGAT1 VNTR polymorphism might be another causal mutation for the BTA14 QTL. However, evidence for Sp1 binding to this polymorphic site and for the capability of DGAT1 VNTR alleles to stimulate gene expression was lacking. In the current work Sp1-VNTR interactions were analyzed by EMSA. In addition, effects of DGAT1 VNTR alleles on gene expression were measured with reporter gene analyses. Conclusions from the results are that 1) the DGAT1 VNTR sequence is indeed a target for Sp1 binding; 2) DGAT1 VNTR alleles can stimulate gene expression in vitro and probably in vivo as well; and 3) although the stimulating effects of the different DGAT1 VNTR alleles did not show significant differences in vitro, their effects on transcription might be different in the chromatin context existing in vivo.Physiological Genomics 04/2006; 25(1):116-20. · 2.73 Impact Factor -
Article: The mutation causing the black-and-tan pigmentation phenotype of Mangalitza pigs maps to the porcine ASIP locus but does not affect its coding sequence.
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ABSTRACT: The gene for agouti signaling protein (ASIP) is centrally involved in the expression of coat color traits in animals. The Mangalitza pig breed is characterized by a black-and-tan phenotype with black dorsal pigmentation and yellow or white ventral pigmentation. We investigated a Mangalitza x Piétrain cross and observed a coat color segregation pattern in the F2 generation that can be explained by virtue of two alleles at the MC1R locus and two alleles at the ASIP locus. Complete linkage of the black-and-tan phenotype to microsatellite alleles at the ASIP locus on SSC 17q21 was observed. Corroborated by the knowledge of similar mouse coat color mutants, it seems therefore conceivable that the black-and-tan pigmentation of Mangalitza pigs is caused by an ASIP allele a(t), which is recessive to the wild-type allele A. Toward positional cloning of the a(t) mutation, a 200-kb genomic BAC/PAC contig of this chromosomal region has been constructed and subsequently sequenced. Full-length ASIP cDNAs obtained by RACE differed in their 5' untranslated regions, whereas they shared a common open reading frame. Comparative sequencing of all ASIP exons and ASIP cDNAs between Mangalitza and Piétrain pigs did not reveal any differences associated with the coat color phenotype. Relative qRT-PCR analyses showed different dorsoventral skin expression intensities of the five ASIP transcripts in black-and-tan Mangalitza. The a(t) mutation is therefore probably a regulatory ASIP mutation that alters its dorsoventral expression pattern.Mammalian Genome 02/2006; 17(1):58-66. · 2.89 Impact Factor -
Article: A major genetic component of BSE susceptibility.
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ABSTRACT: Coding variants of the prion protein gene (PRNP) have been shown to be major determinants for the susceptibility to transmitted prion diseases in humans, mice and sheep. However, to date, the effects of polymorphisms in the coding and regulatory regions of bovine PRNP on bovine spongiform encephalopathy (BSE) susceptibility have been considered marginal or non-existent. Here we analysed two insertion/deletion (indel) polymorphisms in the regulatory region of bovine PRNP in BSE affected animals and controls of four independent cattle populations from UK and Germany. In the present report, we show that two previously reported 23- and 12-bp insertion/deletion (indel) polymorphisms in the regulatory region of bovine PRNP are strongly associated with BSE incidence in cattle. Genotyping of BSE-affected and control animals of UK Holstein, German Holstein, German Brown and German Fleckvieh breeds revealed a significant overrepresentation of the deletion alleles at both polymorphic sites in diseased animals (P = 2.01 x 10(-3) and P = 8.66 x 10(-5), respectively). The main effect on susceptibility is associated with the 12-bp indel polymorphism. Compared with non-carriers, heterozygous and homozygous carriers of the 12-bp deletion allele possess relatively higher risks of having BSE, ranging from 1.32 to 4.01 and 1.74 to 3.65 in the different breeds. These values correspond to population attributable risks ranging from 35% to 53%. Our results demonstrate a substantial genetic PRNP associated component for BSE susceptibility in cattle. Although the BSE risk conferred by the deletion allele of the 12-bp indel in the regulatory region of PRNP is substantial, the main risk factor for BSE in cattle is environmental, i.e. exposure to feedstuffs contaminated with the infectious agent.BMC Biology 02/2006; 4:33. · 5.75 Impact Factor -
Article: Genomewide scan for anal atresia in swine identifies linkage and association with a chromosome region on Sus scrofa chromosome 1.
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ABSTRACT: Anal atresia is a rare and severe disorder in swine occurring with an incidence of 0.1-1.0%. A whole-genome scan based on affected half-sibs was performed to identify susceptibility loci for anal atresia. The analysis included 27 families with a total of 95 animals and 65 affected piglets among them. Animals were genotyped for 126 microsatellite markers distributed across the 18 autosomal porcine chromosomes and the X chromosome, covering an estimated 2080 cM. Single-point and multipoint nonparametric linkage scores were calculated using the computer package ALLEGRO 1.0. Significant linkage results were obtained for chromosomes 1, 3, and 12. Markers on these chromosomes and additionally on chromosomes for which candidate genes have been postulated in previous studies were subjected to the transmission disequilibrium test (TDT). The test statistic exceeded the genomewide significance level for adjacent markers SW1621 (P = 7 x 10(-7)) and SW1902 (P = 3 x 10(-3)) on chromosome 1, supporting the results of the linkage analysis. A specific haplotype associated with anal atresia that could prove useful for selection against the disorder was revealed. Suggestive linkage and association were also found for markers S0081 on chromosome 9 and SW957 on chromosome 12.Genetics 12/2005; 171(3):1207-17. · 4.01 Impact Factor -
Article: Characterization of the bovine ampkgamma1 gene.
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ABSTRACT: AMP-activated protein kinase (AMPK) represents the mammalian form of the core component of a kinase cascade that is conserved between fungi, plants, and animals. AMPK plays a major role in protecting mammalian cells from metabolic stress by switching off biosynthetic pathways that require ATP and switching on ATP-regenerating pathways. In this report, we describe the isolation and characterization of the gene for the noncatalytic bovine gamma1 subunit of AMPK. The bovine ampkgamma1 (PRKAG1) gene spans in excess of 14 kb and is located at BTA 5q21-q22. It consists of 12 exons ranging in size from 38 b to 166 b, interspersed with 11 introns that range between 97 b and 6753 b in length. The coding region of the bovine gene shares 93% and 90% nucleotide sequence similarity with its human and rat counterparts, and the bovine AMPKgamma1 protein is 98% and 95% identical to its human and rat homologs, respectively, in amino acid sequence. SNP discovery using a cattle DNA panel revealed a number of polymorphisms that may be useful for the evaluation of ampkgamma1 as a candidate gene for energy metabolism-related production traits.Mammalian Genome 04/2005; 16(3):194-200. · 2.89 Impact Factor -
Article: Characterization of the bovine ampkγ1 gene
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ABSTRACT: AMP-activated protein kinase (AMPK) represents the mammalian form of the core component of a kinase cascade that is conserved between fungi, plants, and animals. AMPK plays a major role in protecting mammalian cells from metabolic stress by switching off biosynthetic pathways that require ATP and switching on ATP-regenerating pathways. In this report, we describe the isolation and characterization of the gene for the noncatalytic bovine 1 subunit of AMPK. The bovine ampk1 (PRKAG1) gene spans in excess of 14 kb and is located at BTA 5q21–q22. It consists of 12 exons ranging in size from 38 b to 166 b, interspersed with 11 introns that range between 97 b and 6753 b in length. The coding region of the bovine gene shares 93% and 90% nucleotide sequence similarity with its human and rat counterparts, and the bovine AMPK1 protein is 98% and 95% identical to its human and rat homologs, respectively, in amino acid sequence. SNP discovery using a cattle DNA panel revealed a number of polymorphisms that may be useful for the evaluation of ampk1 as a candidate gene for energy metabolism-related production traits.Mammalian Genome 01/2005; 16(3):194-200. · 2.89 Impact Factor -
Article: Evidence for multiple alleles at the DGAT1 locus better explains a quantitative trait locus with major effect on milk fat content in cattle.
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ABSTRACT: A quantitative trait locus (QTL) for milk fat percentage has been mapped consistently to the centromeric region of bovine chromosome 14 (BTA14). Two independent studies have identified the nonconservative mutation K232A in the acylCoA-diacylglycerol-acyltransferase 1 (DGAT1) gene as likely to be causal for the observed variation. Here we provide evidence for additional genetic variability at the same QTL that is associated with milk fat percentage variation within the German Holstein population. Namely, we show that alleles of the DGAT1 promoter derived from the variable number of tandem repeat (VNTR) polymorphism are associated with milk fat content in animals homozygous for the allele 232A at DGAT1. Our results present another example for more than two trait-associated alleles being involved in a major gene effect on a quantitative trait. The segregation of multiple alleles affecting milk production traits at the QTL on BTA14 has to be considered whenever marker-assisted selection programs are implemented in dairy cattle. Due to the presence of a potential transcription factor binding site in the 18mer element of the VNTR, the variation in the number of tandem repeats of the 18mer element might be causal for the variability in the transcription level of the DGAT1 gene.Genetics 09/2004; 167(4):1873-81. · 4.01 Impact Factor -
Article: DGAT1 polymorphism in Bos indicus and Bos taurus cattle breeds.
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ABSTRACT: As a result of multiple QTL-mapping projects in recent years, a quantitative trait locus for milk fat percentage and milk yield has been described on BTA14. Recent reports name the acyl-CoA : diacylglycerol acyltransferase (DGAT1) gene on BTA14 as a potential candidate gene, with a nonconservative substitution of lysine by alanine (K232A) producing a major effect on milk composition and yield. DGAT1K appears to be the ancestral allele and the K232A substitution probably occurred after the divergence of the Bos indicus and Bos taurus lineages. These findings prompted us to genotype 1748 DNA samples of 38 different Bos taurus and Bos indicus cattle breeds from 13 countries on five continents (Europe, Africa, Asia, North America and South America), to examine the occurrence of the DGAT1 polymorphism and characterize the K232A substitution in cattle breeds of different origins and selected for different purposes (e.g., beef, dairy and dual purpose). Calculating pairwise FST values for pooled subpopulations showed least divergence for Bos indicus breeds with high milk fat percentage. Fixation of DGAT1A was found in some Bos taurus breeds and fixation of DGAT1K in one Bos indicus breed. Breeds of no known organized breeding background from the Near East domestication centre of Bos taurus and taurine African N'Dama cattle were found to possess intermediate frequencies of DGAT1K. While beef breeds tended to harbour higher DGAT1A levels, dairy cattle showed everything from very low levels of DGAT1K to unexpectedly high frequencies of this allele.J Dairy Res 06/2004; 71(2):182-7. · 1.57 Impact Factor -
Article: Assessment of the gene content of the chromosomal regions flanking bovine DGAT1.
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ABSTRACT: As a first step towards verifying the candidate status of DGAT1 as the causal gene for milk fat percentage in cattle, we constructed a bovine BAC contig spanning 576 kb of the chromosomal region containing DGAT1. High content of NotI sites (21 within the contig) indicated that the region is gene-rich. Twenty-three genes neighboring DGAT1 were mapped, including two bovine cDNA sequences that have no orthologous sequences within the NCBI sequence databases. On average, 2015 bp for each of the 23 neighboring genes were sequenced and entered into EMBL. Likewise, 10 new STS markers were established by BAC-end sequencing. Within the genes and STS markers, 55 polymorphisms were discovered. These will form the basis of future linkage disequilibrium studies to test whether any genes neighboring DGAT1 are associated with variation in milk fat percentage, thereby testing the candidate status of DGAT1.Genomics 02/2004; 83(1):172-80. · 3.02 Impact Factor -
Article: Molecular cloning, mapping, and functional analysis of the bovine sulfate transporter SLC26a2 gene.
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ABSTRACT: Sulfate is one of the most important macronutrients in cells and the major sulfur source in many organisms as well as one of the most abundant anions in the serum. As sulfate is a hydrophilic anion, movement across the lipid bilayer is mediated by transporters that regulate efflux and influx. Here, we report the molecular cloning, mapping, and functional analysis of the bovine solute carrier/sulfate transporter SLC26a2 gene, the first member of this family to be cloned in cattle. A recombinant phage library was screened, and single phages harbouring the SLC26a2 gene was isolated and sequenced. A fragment of 6295 base pairs (bp) of the bovine SLC26a2 gene harbouring exon 2 and exon 3 was used for further analysis. Similar to the human, ovine, mouse, and rat SLC26a2 gene, the bovine ortholog consists of two coding exons. The open reading frame harbours 2202 nucleotides (nt), coding for a protein of 734 amino acids with a calculated molecular weight of 81.5 kilodaltons (kDa) and a statistical isoelectric point (pI) of 8.77. The bovine SLC26a2 gene was mapped to chromosome 7q23-q24 (BTA 7q23-q24) by fluorescence in situ hybridisation (FISH) analysis. Two point mutations were identified comparing the DNAs of 300 Holstein Frisian cattle, one of them resulting in an isoleucine to serine amino acid exchange at position 520. The Ile520Ser exchange influences the sulfate uptake as measured in primary fibroblasts isolated from testis and in immortalized fibroblastoid bovine cell lines.Gene 12/2003; 319:161-6. · 2.34 Impact Factor
Top co-authors
Top Journals
- Mammalian Genome (5)
- PLoS ONE (3)
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- Journal of applied genetics (2)
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Institutions
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2010–2012
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Technische Universität München
- Chair of Plant Breeding
München, Bavaria, Germany
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2000–2004
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Deutsches Herzzentrum München
München, Bavaria, Germany
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1992–1993
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Texas A&M University
College Station, TX, USA
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