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G A Brockmann

Publications and source records attributed to G A Brockmann.

15 recordsLinked to original sources
PubMed2005

The map expansion obtained with recombinant inbred strains and intermated recombinant inbred populations for finite generation designs.

The generation of special crosses between different inbred lines such as recombinant inbred strains (RIS) and intermated recombinant inbred populations (IRIP) is being used to improve the power of QTL detection techniques, in particular fine mapping. These approaches acknowledge the fact that recombination of linked loci increases with every generation, caused by the accumulation of crossovers appearing between the loci at each meiosis. This leads to an expansion of the map distance between the loci. While the amount of the map expansion of RIS and IRIP is known for infinite inbred generations, it is not known for finite numbers of generations. This gap was closed here. Since the recursive evaluation of the map expansion factors turned out to be complex, a useful approximation was derived.

Chromosome Mapping↗
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↗
PubMed2003

A novel leptin receptor variant with a conservative amino acid substitution (I359 V) in body weight selected and unselected mouse lines.

Recently published results revealed linkage of obesity traits to a chromosomal region near the leptin receptor gene (Lepr) locus in high body weight selected big and fat DU6i mice. The purpose of this study was the search for variants of the Lepr gene in selected and unselected mouse lines as a candidate for different body composition traits. The complete Lepr cDNA sequence was analysed in DU6i mice. In addition, body weight, abdominal fat weight and serum leptin levels were measured in 42 day old, male mice of the strains DU6i, DUKs, Him : OF1 and DBA/2. Sequence comparison to the published wild type sequence revealed three silent mutations and an amino acid exchange (I359 V) in the C2 domain of the putative leptin binding site in the line DU6i. Compared to the high body weight selected mice also unselected lean control DUKs mice and Him : OF1 mice harbour the amino acid substitution, although they show significantly lower values for body weight, abdominal fat weight and serum leptin levels. Therefore, we assume that the mutation in the C2 domain of Lepr alone might not result in impaired leptin binding or signaling.

Amino Acid Sequence↗
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

Comparing mRNA levels of genes encoding leptin, leptin receptor, and lipoprotein lipase between dairy and beef cattle.

Body weight and fat mass vary distinctly between German Holstein (dairy cattle) and Charolais (beef cattle). The aim of this study was to determine whether the expression of the obese (Ob) gene and lipoprotein lipase (LPL) gene in fat tissues and expression of the long isoform leptin receptor (Ob-Rb) gene in the hypothalamus were different between these two cattle breeds. Body weight and the area of longissimus muscle cross-section of German Holstein were lower (P<0.001), while body fat content, as well as the omental and perirenal fat mass were higher (P<0.001), compared to Charolais. Plasma insulin and leptin levels between two cattle breeds were determined by radioimmunoassay. Compared to Charolais, plasma insulin concentrations were significantly higher (P<0.01), and plasma leptin levels were tended to be higher (P<0.1) in German Holstein. Ob mRNA levels in subcutaneous and perirenal fat depots, but not in the omental fat depot, were significantly higher (P<0.05) in German Holstein than in Charolais. LPL mRNA expression in the perirenal fat depot of German Holstein was greater in abundance than that of Charolais. No significantly different LPL mRNA levels were found in subcutaneous and omental fat depots, and Ob-Rb mRNA levels in the hypothalamus between these two cattle breeds (P<0.05). Both Ob and LPL expression was greater in perirenal and omental fat depots than in the subcutaneous fat depot (P<0.05). Data indicated that in bovine the Ob and LPL gene expression levels in perirenal fats are an important index that is associated with body fat content, while Ob-Rb in hypothalamus is not.

Adipose Tissue↗
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↗
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

Genome-wide search for loci controlling serum IGF binding protein levels of mice.

A segregating F(2) pedigree based on two mouse lines (DU6i and DBA/2) with extremely different growth characteristics was generated to search for loci affecting serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) and to estimate their effects on growth and body composition. DU6i is characterized by high body mass and obesity associated with hyperinsulinemia, hyperleptinemia, and elevated serum IGF-I concentrations. Furthermore, significantly elevated serum levels of IGFBP-2, IGFBP-3, and IGFBP-4 were found in DU6i vs. DBA/2 mice. Linkage analysis identified loci with major effects on the serum level of IGFBP-3 on Chromosome 5 at 58 cM (Igfbp3q1; F = 9.9) and on Chromosome 10 at 46 cM (Igfbp3q2; F = 33.8). A locus significantly influencing serum IGFBP-2 levels in males was found on Chromosome 7. Additional linkage was detected in males and females for IGFBP-2 on Chromosomes 8, 11, 14, 17, and X, and for IGFBP-4 on Chromosome 4. Additional loci affecting IGFBPs acted in a sex-specific manner. The identified loci coincide in part with chromosomal regions controlling growth and obesity. Thus, multiple genes or pleiotropic gene effects may be assumed for these chromosomal regions. The identification of quantitative trait loci for IGFBPs as subcomponents of growth regulation and differentiation will further improve the understanding of complex trait regulation.

Animals↗
PubMed2000

Models for chromatid interference with applications to recombination data.

Genetic interference means that the occurrence of one crossover affects the occurrence and/or location of other crossovers in its neighborhood. Of the three components of genetic interference, two are well modeled: the distribution of the number and the locations of chiasmata. For the third component, chromatid interference, there exists only one model. Its application to real data has not yet been published. A further, new model for chromatid interference is presented here. In contrast to the existing model, it is assumed that chromatid interference acts only in the neighborhood of a chiasma. The appropriateness of this model is demonstrated by its application to three sets of recombination data. Both models for chromatid interference increased fit significantly compared to assuming no chromatid interference, at least for parts of the chromosomes. Interference does not necessarily act homogeneously. After extending both models to allow for heterogeneity of chromatid interference, a further improvement in fit was achieved.

Animals↗
PubMed2000

Single QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F(2) variance of growth and obesity in DU6i x DBA/2 mice.

Genes influencing body weight and composition and serum concentrations of leptin, insulin, and insulin-like growth factor I (IGF-I) in nonfasting animals were mapped in an intercross of the extreme high-growth mouse line DU6i and the inbred line DBA/2. Significant loci with major effects (F > 7.07) for body weight, obesity, and muscle weight were found on chromosomes 1, 4, 5, 7, 11, 12, 13, and 17, for leptin on chromosome 14, for insulin on chromosome 4, and for IGF-I on chromosome 10 at the Igf1 gene locus itself and on chromosome 18. Significant interaction between different quantitative trait loci (QTL) positions was observed (P < 0.01). Evidence was found that loci having small direct effect on growth or obesity contribute to the obese phenotype by gene-gene interaction. The effects of QTLs, epistasis, and pleiotropy account for 64% and 63% of the phenotypic variance of body weight and fat accumulation and for over 32% of muscle weight and serum concentrations of leptin, and IGF-I in the F(2) population of DU6i x DBA/2 mice. [The quantitative trait loci described in this paper have been submitted to the Mouse Genome Database.]

Animals↗
PubMed1999

Fat storage capacity in growth-selected and control mouse lines is associated with line-specific gene expression and plasma hormone levels.

OBJECTIVE: For a detailed understanding of the complex traits growth and fat storage, a dissection into single genetic entities is mandatory. Therefore, blood plasma concentrations of hormones and the expression of selected genes were measured in extremely differentiated mouse lines. Genes were selected as candidates which might influence the complex traits body weight and fat accumulation, and which are located in chromosomal regions recently identified to affect trait differences between the lines. SUBJECTS AND MEASUREMENTS: The mouse lines were selected for high body weight (DU6), high carcass protein content (DU6P) and unselected controls (DUKs). In the selected lines DU6 and DU6P, mean body weights at the age of six weeks were about twice as high as the DUKs, whereas total fat weight was increased 2.2-fold in DU6 mice compared to DU6P and 3.2-fold in comparison to DUKs. Blood plasma concentrations of insulin-like growth factor 1 (IGF-1), growth hormone (GH), insulin and leptin, were measured in all lines at three weeks and at six weeks of age. Expression patterns of the genes encoding growth hormone (Gh), insulin-like growth factor 1 (Igf1), lipoprotein lipase (Lpl), glycerolphosphate dehydrogenase 1 (GDC-1), and adipocyte protein 2 (Ap2) were analyzed by Northern blot hybridization. RESULTS: In line DU6, highly significant increased concentrations of insulin and leptin were observed at six weeks of age; at this stage, IGF-1 concentrations were elevated in the two selected lines compared to controls with maximal concentrations of IGF-1 and GH in DU6P. The amount of mRNA for GH in the pituitary gland, for Igf1 in the liver and for LPL in epididymal fat tissue was significantly elevated in the two selected lines compared to controls at the age of three weeks, but not at six weeks. IGF-1 and GDC-1 mRNA concentrations were significantly higher in the DU6 mice than in the DU6P (P < 0.01) and the DUKs (P < 0.001) mice examined at both ages. CONCLUSIONS: The results prove line-specific concentrations of the analyzed hormones and the transcription amounts of Gh, Igf1, GDC-1 and Lpl. The measured differences are either direct genetic effects or secondary changes, resulting from different food consumption.

Adipocytes↗
PubMed1998

Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth.

Quantitative trait loci (QTL) influencing body weight were mapped by linkage analysis in crosses between a high body weight selected line (DU6) and a control line (DUKs). The two mouse lines differ in body weight by 106% and in abdominal fat weight by 100% at 42 days. They were generated from the same base population and maintained as outbred colonies. Determination of line-specific allele frequencies at microsatellite markers spanning the genome indicated significant changes between the lines on 15 autosomes and the X chromosome. To confirm these effects, a QTL analysis was performed using structured F2 pedigrees derived from crosses of a single male from DU6 with a female from DUKs. QTL significant at the genome-wide level were mapped for body weight on chromosome 11; for abdominal fat weight on chromosomes 4, 11, and 13; for abdominal fat percentage on chromosomes 3 and 4; and for the weights of liver on chromosomes 4 and 11, of kidney on chromosomes 2 and 9, and of spleen on chromosome 11. The strong effect on body weight of the QTL on chromosome 11 was confirmed in three independent pedigrees. The effect was additive and independent of sex, accounting for 21-35% of the phenotypic variance of body weight within the corresponding F2 populations. The test for multiple QTL on chromosome 11 with combined data from all pedigrees indicated the segregation of two loci separated by 36 cM influencing body weight.

Alleles↗
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↗