Biomedical subjects

N Reinsch

Publications and source records attributed to N Reinsch.

18 recordsLinked to original sources

PubMed2006

Mapping of quantitative trait loci for lactation persistency traits in German Holstein dairy cattle.

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.

Animals↗

PubMed2006

Characterization of the DGAT1 mutations and the CSN1S1 promoter in the German Angeln dairy cattle population.

The identification of quantitative trait loci (QTL) and genes with influence on milk production traits has been the objective of various mapping studies in the last decade. In the centromeric region of Bos taurus autosome (BTA) 14, the acyl-CoA:diacylglycerol acyltransferase1 gene (DGAT1) has been identified as the most likely causative gene underlying a QTL for milk fat yield and content. Recently, a second polymorphism in the promoter of DGAT1 emerged as an additional source of variation. In this study, the frequencies and the effects of alleles at the DGAT1 K232A and at the DGAT1 promoter variable number of tandem repeat (VNTR) locus on BTA14, and of alleles at the CSN1S1 (alpha(S1)-casein-encoding gene) promoter on BTA6 in the German Angeln dairy cattle population were investigated. Analyzed traits were milk, fat, protein, lactose, and milk energy yield, fat, protein, lactose, and milk energy content and somatic cell score. The lysine variant of the DGAT1 K232A mutation showed significant effects for most of the milk production traits. A specific allele of the DGAT1 promoter VNTR showed significant effects on the traits lactose yield and content, milk energy content, and SCS compared with the other alleles. Additionally, a regulation mechanism between the DGAT1 K232A mutation and the DGAT1 promoter VNTR was found for fat yield and content, which could be caused by an upper physiological bound for the effects of the DGAT1 gene. At the CSN1S1 promoter, 2 of 4 alleles showed significant allele substitution effects on the milk yield traits.

Alleles↗

PubMed2005

Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3.

BACKGROUND: In long QT syndrome (LQTS), prolongation of the QT-interval is associated with sudden cardiac death resulting from potentially life-threatening polymorphic tachycardia of the torsade de pointes (TdP) type. Experimental as well as clinical reports support the hypothesis that calcium channel blockers such as verapamil may be an appropriate therapeutic approach in LQTS. We investigated the electrophysiologic mechanism by which verapamil suppresses TdP, in a recently developed intact heart model of LQT3. METHODS AND RESULTS: In 8 Langendorff-perfused rabbit hearts, veratridine (0.1 microM), an inhibitor of sodium channel inactivation, led to a marked increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p < 0.05) thereby mimicking LQT3. In bradycardic (AV-blocked) hearts, simultaneous recording of up to eight epi- and endocardial MAPs demonstrated a significant increase in total dispersion of repolarization (56%, p < 0.05) and reverse frequency-dependence. After lowering potassium concentration, veratridine reproducibly led to early afterdepolarizations (EADs) and TdP in 6 of 8 (75%) hearts. Additional infusion of verapamil (0.75 microM) suppressed EADs and consecutively TdP in all hearts. Verapamil significantly shortened endocardial but not epicardial MAPs which resulted in significant reduction of ventricular transmural dispersion of repolarization. CONCLUSIONS: Verapamil is highly effective in preventing TdP via shortening of endocardial MAPs, reduction of left ventricular transmural dispersion of repolarization and suppression of EADs in an intact heart model of LQT3. These data suggest a possible therapeutic role of verapamil in the treatment of LQT3 patients.

Action Potentials↗

PubMed2005

Mapping and exclusion mapping of genomic imprinting effects in mouse F2 families.

Parent-of-origin effects were mapped by multimarker regression analysis in a cross between a high body weight selected line (DU6) and a control line (DUKs). The difference between F(2) progeny being heterozygous Qq and qQ (first allele is paternally derived) for grandpaternal Q and grandmaternal q alleles was genome-wide significant for the traits liver weight and spleen weight with a paternal imprinting effect at 1 cM on proximal chromosome 11. Suggestive imprinting effects (chromosome-wide error probability less than 0.05) were found for the traits body weight, liver weight, and kidney weight, and were located on chromosome 14 at 25 cM, 23 cM, and 32 cM, respectively. A genome-wide significant quantitative trait locus (QTL) for spleen weight at 26 cM slightly failed the suggestive significance level for imprinting. The effect was consistently maternal for all these traits on chromosome 14. Further suggestive imprinting effects were found for abdominal fat percentage on chromosome 3, for spleen weight on chromosome 5, and for liver weight on chromosome X. Our results are supported by a likely imprinting in a human genome region with homology to mouse chromosome 14 and agree well with the known imprinting of proximal chromosome 11 in the mouse.

Animals↗

PubMed2004

The DGAT1 K232A mutation is not solely responsible for the milk production quantitative trait locus on the bovine chromosome 14.

The gene, acyl-CoA:diacylglycerol acyltransferase1 (DGAT1), was recently identified as the one underlying the quantitative trait locus (QTL) for milk production traits in the centromeric region of the bovine chromosome 14. Until now, 2 alleles, the lysine variant (increasing fat yield, fat and protein percentage) and the alanine variant (increasing protein and milk yield), were postulated at DGAT1. This study investigated whether the diallelic DGAT1 polymorphism is responsible for all the genetic variation at the centromeric region of this chromosome for milk, fat, and protein yield and fat and protein percentage. A statistical model was applied to a granddaughter design to analyze 16 German Holstein families. The model included the diallelic DGAT1 effect and the QTL transition probability estimated for each chromosomal position by a multiple marker approach. Because the regression coefficient of this probability was corrected for the diallelic DGAT1 polymorphism, it represented a putative conditional QTL effect. The effect of the DGAT1 gene was always highly significant. The conditional QTL effect was significant genomewise for fat percentage at the proximal end of the chromosome and for protein percentage at a more distal chromosomal region. Additional chromosomewise significance was found for fat and protein yield. Our results suggest an additional source of genetic variance on this chromosome for these traits; either one or more additional alleles segregating at DGAT1 that were not previously detected, a second quantitative trait locus affecting these traits, or both.

Acyltransferases↗

PubMed2003

Quantitative trait loci mapping of functional traits in the German Holstein cattle population.

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.

Animals↗

PubMed2002

Mapping of the bovine blood group systems J, N', R', and Z show evidence for oligo-genetic inheritance.

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.

Animals↗

PubMed2002

Frequency and heritability of supernumerary teats in German simmental and German Brown Swiss cows.

The incidence of supernumerary teats has been recorded in 179,793 German Simmental and 37,460 German Brown Swiss cows. Data were collected from first-crop daughters of test bulls from 1987 to 1998. The number of sires was 4,298 and 1,039, respectively. The average frequency of affected animals was 44.3% in German Simmental and 31.2% in German Brown Swiss. A significant yet small effect was found for herd-book membership (yes/no) and, in the Simmental data only, for inspector. The impact of year of birth and year of inspection was also significant, and more important, reflected a decrease of the population averages with time. Surprisingly, the incidence of supernumerary teats increased significantly with the parity number of dams in both breeds. A Bayesian threshold animal model approach was used to estimate the heritability of the occurrence of supernumerary teats. The posterior mean for the heritability was h2 = 0.45 in German Simmental and h2 = 0.43 in Brown Swiss, with standard errors of 0.01 and 0.03, respectively. Ranks of sires obtained from threshold and linear models showed a rank correlation of roughly 0.8 in both breeds. For a sound identification of the worst sires, a threshold model is recommended.

Animals↗

PubMed2001

A whole genome scan for differences in recombination rates among three Bos taurus breeds.

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.

Animals↗

PubMed2001

A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14.

As part of a genome scan, ESTs derived from mammary gland tissue of a lactating cow were used as candidate genes for quantitative trait loci (QTL), affecting milk production traits. Resource families were genotyped with 247 microsatellite markers and 4 polymorphic ESTs. It was shown by linkage analysis that one of these ESTs, KIEL_E8, mapped to the centromeric region of bovine Chromosome (Chr) 14. Regression analysis revealed the presence of a QTL, with significant effect on milk production, in this chromosome region, and analysis of variance showed no significant interaction of marker genotype and family. The estimated significant differences between homozygous marker genotypes were 140 kg milk, -5.02 kg fat yield, and 2.58 kg protein yield for the first 100 days of lactation. Thus, there was strong evidence for a complete or nearly complete linkage disequilibrium between KIEL_E8 and the QTL. To identify the biological function of KIEL_E8, we extended the sequence for 869 bp by 5'-RACE. A 560-bp fragment of this shows a 90.9% similarity to a gene encoding a cysteine- and histidine-rich cytoplasmic protein in mouse. Although such a protein may have a regulatory function for lactation and a linkage disequilibrium between the EST marker and the QTL has been observed, it remains to be elucidated whether they are identical or not. Nevertheless, KIEL_E8 will be an efficient marker to perform marker-assisted selection in the Holstein-Friesian population.

Alleles↗

PubMed2000

A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle.

A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.

AMP-Activated Protein Kinases↗

PubMed2000

Consensus and comprehensive linkage maps of bovine chromosome 7.

The objective of this project was to integrate the currently available linkage maps for bovine chromosome 7 (BTA7) by combining data sets from eight research groups. A total of 54 unique markers were typed in eight pedigrees. Multilocus linkage analysis with CRI-MAP produced a bovine chromosome 7 consensus framework map of 27 loci ordered with odds greater than 1000:1. Furthermore, we present a bovine chromosome 7 comprehensive map integrating 54 loci. The locus order is in general agreement with the recently published linkage maps except for one discrepancy. The order of loci BM9289, BMS713, and ILSTS001 was reversed in the consensus framework map relative to the published USDA-MARC bovine chromosome 7 linkage map.

Animals↗

PubMed2000

[Study of mapping QTLs for milk traits on the German dairy cattle].

A total of 1,130 bulls belonging to 20 half-sib families of German dairy cattle were genotyped for 229 microsatellite markers on 30 chromosomes. The data were used in an attempt to map quantitative trait loci applying regression as multiple-marker regression. For association analysis with a granddaughter design, the estimated breeding values for 3 milk traits were used: milk production, fat production and protein production. The empirical values of significance thresholds were determined by using a permutation test on the experimental data. Several significant QTLs were found on some chromosomes, especially on the chromosome 14. The results give a strong support for the experiments of Coppieters et al. and Ron et al.

Animals↗

PubMed1999

Bovine chromosome 4 workshop: consensus and comprehensive linkage maps.

The report of the bovine chromosome 4 (BTA4) workshop is presented. Six laboratories contributed a total of 30,168 informative meioses from 62 loci. Twenty-two loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of BTA4. The remaining 40 loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 131.4 cM. The female map was 124.3 cM in length, while the male map was 134.3 cM. The comprehensive sex-averaged map spanned 141.6 cM. The length of the female and male comprehensive maps were 123.1 cM and 156.4 cM, respectively. Average genetic distance between loci was 6 and 2.3 cM for the consensus and comprehensive linkage maps, respectively.

Animals↗

PubMed1999

Monitoring daily milk yields with a recursive test day repeatability model (Kalman filter).

Mixed model methodology and recursive estimation techniques (Kalman filter) were combined to detect significant changes in the performance level of both individual cows and an entire herd. Yields were predicted for the next time of recording using all data available up to that time. Predicted yields were compared with actual measurements. If the error of prediction, or innovation, exceeded +/- 2 times its standard deviation, the observation was considered to be significantly different from the former yield level. The data comprised 30,199 records for 135 cows and 366 d. Effects fitted in the model were test day, breed, and lactation class as fixed effects and cow within lactation number as a random effect. A lactation curve was fitted within lactation class. Of the observed milk yields, 9.2% deviated significantly from the expected value in a negative direction. None of the innovation of the fixed-day effect exceeded the threshold of two standard deviations. Compared with the results of rolling average, which were calculated as the average of a 10-d period, over 20% of the observations of the daily milk yield were classified differently by the two methods. The mixed-model method for recursive estimation takes better account of environmental and lactational effects influencing daily milk yields as the rolling average. The mixed-model recursive estimation method was applicable for the detection of suspicious (i.e., outside a specified prediction interval) observations of individual cows at the time of the actual recording.

Animals↗

PubMedDate not supplied

A QTL for the degree of spotting in cattle shows synteny with the KIT locus on chromosome 6.

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.

Animals↗

PubMedDate not supplied

Mapping of QTL for Body Conformation and Behavior in Cattle.

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.

Animals↗

PubMedDate not supplied

A high-density linkage map of the RN region in pigs.

The porcine RN locus affects muscle glycogen content and meat quality. We previously mapped the RN locus to chromosome 15. This study describes the identification of polymorphisms for four class I and four class II markers located in the RN region. Resource families were genotyped with F-SSCP markers (fluorescent single strand conformation polymorphism) and microsatellite markers. Subsequent multipoint linkage analysis revealed the order FN1-IGFBP5-S1000-S1001-IL8RB-VIL1-RN-Sw936-Sw906. The gene order is identical to the previously reported porcine RH map of the same region. The described map will facilitate positional cloning of the RN gene.

Journal Article↗