Response to divergent selection for insulin-like growth factor-I concentration and correlated responses in growth traits in Angus cattle.

A divergent selection experiment for serum IGF-I concentration was established in 1989 at the Eastern Agricultural Research Station located in Belle Valley, Ohio. One hundred spring-calving (50 high line and 50 low line) and 100 fall-calving (50 high line and 50 low line) cows with unknown IGF-I concentrations were randomly assigned to the 2 divergent selection lines. Results of this study included 2,507 calves from the 1989 through 2005 calf crops. (Co)variance components were estimated for direct and maternal additive genetic effects using an animal model and multiple-trait, derivative-free, REML (MTDFREML) computer programs. Estimated breeding values were also obtained and regressed on years to estimate direct and correlated responses to divergent selection for serum IGF-I concentration. Estimates of direct heritability for growth traits from a single trait model were moderate and ranged from 0.33 ± 0.06 for birth weight to 0.42 ± 0.06 for preweaning BW gain. Heritability estimates for direct effects were 0.44 ± 0.07, 0.43 ± 0.07, 0.35 ± 0.06, and 0.48 ± 0.07 for IGF-I concentration at d 28, 42, and 56 of the 140-d postweaning period, and for mean IGF-I concentration, respectively. Maternal heritability and the proportion of phenotypic variance due to permanent environment effect of dam were ≤0.25 for growth traits and IGF-I concentrations. Cattle in the high line had significantly (P < 0.001) greater direct effects of mean IGF-I concentration than those in low line (high line: 66.92 ± 4.40 ng/mL vs. low line: -40.82 ± 5.18 ng/mL) in 2005. Direct responses per year for mean IGF were 5.18 ng/mL in the high line and -3.76 ng/mL in the low line. The regression of direct effects of preweaning BW gain on year were not significantly different from zero in either the high or low line. However, genetic trends were negative and significant for birth weight and postweaning BW gain in the high line and were positive and significant in the low line. Results demonstrated that divergent selection for serum IGF-I concentration in beef cattle will change the genetic potential for IGF-I concentration and that selection for lesser IGF-I concentration will result in increased birth weights and postweaning BW gains.

Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle.

The Pit-1 gene was studied as a candidate for genetic markers of growth and carcass traits. Angus beef cattle that were divergently selected for high- or low-blood serum IGF-I concentration were used in this study. The single-strand conformation polymorphism method was used to identify polymorphism in the Pit-1 gene including regions from intron 2 to exon 6. Two polymorphisms, Pit1I3H (HinfI) and Pit1I3NL (NlaIII), were detected in intron 3 of the Pit-1 gene. One polymorphism, Pit1I4N (BstNI), was found in intron 4, and a single nucleotide polymorphism, Pit1I5, was found in intron 5. The previously reported polymorphism in exon 6, Pit1E6H (HinfI), was also studied in 416 Angus beef cattle. Associations of the polymorphisms with growth traits, carcass traits, and IGF-I concentration were analyzed using a general linear model procedure. No significant associations were observed between these polymorphisms and growth and carcass traits.

Association of single nucleotide polymorphisms in the growth hormone and growth hormone receptor genes with blood serum insulin-like growth factor I concentration and growth traits in Angus cattle.

This study was conducted to identify polymorphisms in the promoter and coding regions of the bovine growth hormone and growth hormone receptor genes and to study association of polymorphisms identified in these genes with growth traits and serum insulin-like growth factor-I (IGF-I) concentration. The denaturing gradient gel electrophoresis method and sequencing were utilized to identify three new single nucleotide polymorphisms in the promoter region of the growth hormone gene in Angus cattle. Polymerase chain reaction-based restriction fragment length polymorphism procedures were developed for rapid determination of the single nucleotide polymorphism genotypes in the growth hormone and the growth hormone receptor genes among Angus calves from lines divergently selected for high or low blood serum IGF-I concentration. The IGF-I concentration and growth traits were analyzed using animal models. The single nucleotide polymorphism in the promoter region of the growth hormone receptor gene was associated with serum IGF-I concentration on d 42 of the postweaning test and with mean IGF-I concentration. The associated effects of the markers need to be verified in other populations.

Association of a genetic marker with blood serum insulin-like growth factor-I concentration and growth traits in Angus cattle.

The objective of this research was to evaluate a biallelic genetic marker identified in the first promoter region of the bovine IGF-I gene. The point mutation was identified as a T-to-C transition by sequencing the polymorphic fragments. A PCR-RFLP procedure was developed for determining the marker genotypes. Marker genotypes were determined for 760 Angus calves from divergent lines that were created by selection for high or low serum IGF-I concentration (allele A: 63.9%, B: 36.1%). Data were analyzed using the multiple-trait derivative-free restricted maximum likelihood computer programs with animal models. The full animal model included fixed effects of marker genotype, birth year, season of birth, sex, age of dam, and selection line; random effects of animal, maternal genetic, and maternal permanent environmental effects; and a covariate for age of calf. Traits analyzed included blood serum IGF-I concentrations on d 28, 42, and 56 of the postweaning test, mean IGF-I concentration, birth weight, weaning weight, on-test weight, off-test weight, off-test hip height, postweaning gain, and weight gain during the 20-d period immediately after weaning. Results from the analysis across selection lines showed a significant association of the BB genotype with higher weight gain during the first 20 d after weaning and a slight dominance effect of the marker on postweaning gain. Analysis within the low IGF-I line also showed a significant association of the BB genotype with higher weight gain during the first 20 d after weaning and with on-test weight, although analysis within the high IGF-I line did not show any significant association. The associated effects of the marker need to be verified in other cattle populations.

Detection of nucleotide variations in the D-loop region of bovine mitochondrial DNA using polymerase chain reaction-based methodologies.

Allele-specific polymerase chain reaction (ASPCR) and single-strand conformation polymorphism (SSCP) were used to characterize 16 Holstein maternal lines. ASPCR was used to detect polymorphic nucleotides at eight different positions in the displacement loop (D-loop) of bovine mitochondrial DNA (mtDNA): 16022, 16057, 16074, 16231, 16247, 106, 169 and 363. ASPCR analysis of the maternal lines showed variations at nucleotide positions 106, 169, and 363 of the mtDNA. Within-line variation was observed in five maternal lines for nucleotide 363. SSCP analysis of the mtDNA D-loop region revealed variations that classified the maternal lines into six different genotypes. Based upon the variations observed by ASPCR and SSCP analysis, the animals representing the 16 maternal lines could be assigned to 10 different genotypic groups. These procedures provide a rapid, simple, non-radioactive, and reliable method of detecting polymorphism in the D-loop region of bovine mtDNA.

A male linkage map of the cattle (Bos taurus) genome.

A male linkage map of the cattle (Bos taurus) genome was constructed using nine large half-sib families. The map consists of 269 loci, of which 249 are microsatellites and 20 are structural genes. Among the 249 microsatellites, 140 are markers selected from other maps and 98 are new assignments. Chromosome assignment were established for 35 new markers by somatic cell hybrid analysis, of which 26 were confirmed by linkage analysis. Genome coverage is 1975 cM contained within terminal markers on all 29 autosomes. The average distance between adjacent loci is 9.7 cM, with 72.1% of the map intervals < or = 15 cM and 4.9% of the intervals > or = 25 cM. The inclusion of mapped markers permitted integration and comparisons with other maps, facilitating the identification of discrepancies in chromosome assignment, gene order, and map distance. The inclusion of Type I and blood group markers in the map was useful for comparative mapping, revealing possible blood group orthologies between humans and cattle. The map generated will serve as a useful tool for comparative mapping, mapping of quantitative trait loci and marker assisted selection.

Polymorphism of bovine MHC class I genes. Joint report of the Fifth International Bovine Lymphocyte Antigen (BoLA) Workshop, Interlaken, Switzerland, 1 August 1992.

The objectives of the Fifth International BoLA Workshop were to: standardize nomenclature, compare typing methods, and characterize BoLA haplotypes. The workshop was based on the distribution of blood samples (cells) from 60 selected cattle to 14 laboratories. Results for the class I (BoLA-A) region are presented in this paper while results for the class II regions are presented in a separate report. Thirty-six of the 50 previously established serological class I specificities were represented in the cell panel. However, only 30 specificities could be confirmed. Two specificities, A16 and A32, were upgraded from provisional, workshop (w) specificities to BoLA-A locus specificities and three new specificities, w51(w28), w52 and w53(w28), were defined. The 39 specificities distinguished 30 class I haplotypes in the 60 animals. Class I isoelectric focusing proved to be a useful adjunct to the serology. Isoelectric focusing confirmed several serologically defined splits and detected splits of A15(A8), A18(A6) and A22(w49) that had not been detected by serology. Subsequently, serological support for splits of A15(A8) and A22(w49) was found.

Linkage of bovine erythrocyte antigen loci B, C, L, S, Z, R' and T' and the serum protein loci post-transferrin 2 (PTF 2), vitamin D binding protein (GC) and albumin (ALB) to DNA microsatellite markers.

Seven bovine erythrocyte antigen loci and three serum protein loci were tentatively assigned to chromosomes or synteny groups by linkage analysis to previously assigned microsatellite DNA markers. The erythrocyte antigen locus EAB was mapped to synteny group U27; EAC to chromosome 18, synteny group U9; EAL to chromosome 3, synteny group U6; EAS to chromosome 21, synteny group U4; EAZ to chromosome 10, synteny group U5; EAR' to chromosome 16, synteny group U1; and EAT' to chromosome 19, synteny group U21. The vitamin D binding protein (GC) and albumin (ALB) loci were assigned to chromosome 6, synteny group U15 and post-transferrin 2 (PTF 2) to chromosome 19, synteny group U21.

The bovine B and C blood group systems are not likely to be the orthologues of human RH: an interesting twist in the comparative map.

We tested the hypothesis that either the bovine B or C blood group system is the orthologue of human RH. A comparative linkage mapping strategy was applied, using blood typing and restriction fragment length polymorphism (RFLP) analysis of four loci linked to RH on HSA1; PGD, FGR, ALPL and FUCA1. Four sires with a total of 255 half-sib offspring were used for the linkage analysis. Strong support for linkage between ALPL, FUCA1 and FGR was obtained for all sire families (lod scores > 11 for all pairwise comparisons). This new linkage group was assigned to bovine synteny group U17 based on previous somatic cell mapping of the FGR locus. The most favoured order is ALPL-FUCA1-FGR (2.18:1), with ALPL and FGR 5.4 CM and 6.3 CM, respectively, from FUCA1. The B and C blood group systems and PGD were genetically independent of each other and all other markers, indicating that neither B nor C is likely to be the bovine orthologue of human RH. However, given available comparative mapping data, there is some chance that the bovine orthologue of RH is on bovine synteny group U6. Although gene order appears to be conserved with humans, the differences in recombination rates between these three loci in cattle, humans and mice strongly suggest that it is not possible to use human map distances to predict map distances in cattle, making it imperative that bovine gene mappers continue to emphasize adding type I markers to the bovine linkage map.

Association between the bovine major histocompatibility complex and chronic posterior spinal paresis--a form of ankylosing spondylitis--in Holstein bulls.

A highly significant association was found between the bovine MHC class I antigen BoLA-A8 and a form of vertebral osteophytosis/ankylosing spondylitis known as chronic posterior spinal paresis (PSP) in Holstein bulls (P < 0.001). In a population study, restricted to unrelated bulls, BoLA-A8 was significantly associated with PSP (P = 0.0015) with a relative risk of 34.6. In a family study, one PSP bull, BoLA A8/A20, sired 13 offspring. BoLA-A8 was significantly associated with PSP (P = 0.0008). All five PSP sons inherited the A8 allele and the eight healthy sons each inherited the A20 allele. In three other families a complete association of BoLA-A8 and PSP was observed. Lod score analysis, using all available families, indicated a significant linkage between BoLA and PSP (lod score = 6.9). Based on clinical observation, pathology, age/sex predilection, and a strong association with a class I MHC molecule, this inflammatory disease appears analogous to the human condition known as ankylosing spondylitis.

Joint Report of the Fourth International Bovine Lymphocyte Antigen (BoLA) Workshop, East Lansing, Michigan, USA, 25 August 1990.

Blood samples from 54 animals were exchanged between 15 laboratories in nine countries to improve and expand BoLA class I and class II typing. A total of 27 out of 33 (82%) of previously accepted BoLA-w specificities were represented within the cell panel. Seventeen new serum-defined BoLA specificities were accepted by the workshop participants, thus expanding the number of internationally recognized BoLA specificities to 50. The large number of new specificities detected resulted from the number of serological reagents used (n = 1139) and the genetic diversity of the cell panel. Confidence derived from the high percentage of agreement between the laboratories on antigen detection (97.3%; r = 0.84) permitted the removal of the workshop (w) notation from 23 BoLA-w specificities and their acceptance as full status BoLA-A antigens. Two new non-BoLA antigens were also detected, one completely included within the red blood cell factor S' (BoLy-S'), whereas a second (BoLy-w1) did not show any association with tested red blood cell factors. A comparison between serological, isoelectric focusing (IEF) and DNA typing for BoLA class II polymorphism was conducted with a subset of workshop cells. Correlation between the three methods was significant for three combinations of alleles. Three other serologically defined class II specificities were correlated with DR and/or DQ restriction fragment length polymorphism (RFLP) types, whereas six additional IEF types were correlated with DR and/or DQ RFLP types (r greater than or equal to 0.50). Several new IEF, DRB, DQA and DQB RFLP patterns were identified. In 46 animals that were typed for BoLA-DR and DQ genes by RFLP analysis, 46 different BoLA haplotypes were tentatively defined. These 46 haplotypes were distinguished by 31 serologically-defined BoLA-A alleles (and 2 'blanks'), 15 DRB RFLP types (plus up to 10 new DRB RFLP patterns) and 23 DQA-DQB haplotypes.