Genetic mapping of BoLA-A, CYP21, DRB3, DYA, and PRL on BTA23.
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Biomedical subjects
Publications and source records attributed to Y Da.
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Polar body and oocyte typing is a new technique for gene-centromere mapping and for generating female linkage maps. A maximum likelihood approach is presented for ordering multiple markers relative to the centromere and for estimating recombination frequencies between markers and between the centromere and marker loci. Three marker-centromere orders are possible for each pair of markers: two orders when the centromere flanks the two markers and one order when the centromere is flanked by the two markers. For each possible order, the likelihood was expressed as a function of recombination frequencies for two adjacent intervals. LOD score for recombination frequency between markers or between the centromere and a marker locus was derived based on the likelihood for each gene-centromere order. The methods developed herein provide a general solution to the problem of multilocus gene-centromere mapping that involves all theoretical crossover possibilities, including four-strand double crossovers.
A panel of 81 new polymorphic bovine microsatellite markers is described, together with further information on a previously reported group of 16 markers. The mean polymorphism information content of the 97 markers determined in 20 cattle was 0.66. Seventy-three of these markers have been assigned to chromosomes by either linkage analysis or use of hybrid cell panels. Thirty-nine of the markers were polymorphic in sheep, and 32 were polymorphic in goat. This study identified a set of 18 robust markers that were polymorphic in all three species and that covered 14 bovine chromosomes. This provides a single group of markers, which would be suited to genetic distance analysis and parentage control in cattle, sheep and goat.
Individual loci affecting economic traits can be located using genetic linkage. Application of either daughter or granddaughter design requires determination of allele origin in the progeny. If only the sires and their progeny are genotyped, the paternal allele origin of progeny having the same genotype as the sire cannot be determined. The expected frequency of informative sons can be predicted for each sire and genetic marker from the allele frequencies in the population. The accuracy of a predictor of the frequency of informative progeny was tested on 103 grandsire x microsatellite combinations. Number of sons per grandsire varied from 24 to 129. Allele frequencies in the population were estimated by genotyping seven sires. The regression of the frequency of informative sons on the predicted frequency was 1.04 with a zero intercept model. Thus, considering the large number of genetic markers available for analysis, predicted informative frequency is a useful criterion for selection of genetic markers.
A male-specific genetic linkage map of nine loci on bovine Chromosome (Chr) 2 (BTA2) was constructed from 306 offspring belonging to six paternal half-sib families. Loci studied were the structural genes for liver/bone/kidney alkaline phosphatase (ALPL). Gardner-Rasheed feline sarcoma (v-fgr) oncogene homolog (FGR), alpha-L-fucosidase 1 (FUCA1), and fibronectin 1 (FN1), and the microsatellite loci ARO28, DU17S2, DU17S3, DU17S4, and DU17S5. Genotyping was performed by restriction fragment length polymorphism (RFLP) for structural genes and polymerase chain reaction (PCR) for the microsatellites. Two genetically independent linkage groups were identified. The order of genes in the first linkage group, L31, is (ARO28-FN1)-FGR-FUCA1-ALPL, covering a map distance of 34.1 cM between terminal markers. The second linkage group, L32, consists of DU17S2-DU17S5-DU17S4-DU17S3 and is 41.3 cM in length. Genetic linkage between FN1 and FGR confirms previous physical assignment of these genes to the same synteny group. Currently, the genetic linkage of FN1 and FGR is unique to cattle and thus localizes a site of chromosomal evolution to a 22-cM interval between the two loci.
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.
Effects of bovine leukemia virus (BLV) infection on milk and fat yields were studied by using data collected from Holstein cows over a 6-year period. Milk and fat yields in BLV-infected cows with persistent lymphocytosis (PL) declined significantly relative to their BLV-infected non-PL herdmates. Declines were most pronounced in cows older than 6 years. The estimated loss to the dairy industry due to PL is more than $42 million annually. A major histocompatibility complex class I (BoLA-A) allele that has been previously associated with resistance to PL was associated with longevity and realization of milk production potentials, indicating that genetic resistance to PL will have an economic benefit in herds where BLV is endemic.
We have developed a method of analyzing individual cells to detect proviral DNA of the bovine leukemia virus (BLV) using flow cytometry and PCR. Individual cells of the BL3* cell line, which contain multiple integrated copies of the BLV provirus, and the uninfected cell line BL3(0), were sorted into wells of a 96-well plate. Following cell lysis, portions of the BLV envelope (ENV) and cellular prolactin (PRL) genes were amplified simultaneously using PCR. Viral and cellular products of first-round PCR were amplified separately in a second round of PCR using "heminested" primers. Separation of the PCR products by polyacrylamide gel electrophoresis yielded distinct fragments of the predicted sizes. The operational sensitivity of this method for the detection of virus was > 90% when testing single infected cells. In addition, we were able to reliably amplify DNA from a single BL3* cell among as many as 10(5) BL3(0) cells and established that the sensitivity for detecting a single infected cell among 20, 100, or 1000 uninfected cells was at least 90%. Estimates of low percentages of infected cells were obtained by applying probability theory to results of experiments conducted on wells containing more than one cell. Using these methods, B lymphocytes obtained from the peripheral blood of BLV-infected cattle were tested for proviral DNA. BLV ENV was identified in 76.9 +/- 4.9% of single B cells tested from a seropositive animal with persistent lymphocytosis (PL), but in only 0.033 +/- 0.009% of B cells from another seropositive cow without PL.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic parameters of somatic cell scores for Holstein cows were estimated using an animal model and REML for two data sets. Set 1, with 13,017 records from 5278 cows, was used to obtain variance components, heritability, and repeatability for two lactation measures: the simple average and the weighted average of test day data. Set 2, with 14,418 records from 4806 cows, was used to obtain genetic correlations for the simple average between lactations 1 and 2, between lactations 1 and 3, and between lactations 2 and 3. Simple and weighted average of test day somatic cell scores had the same heritabilities (.12) and repeatabilities (.35). Phenotypic variances were about 1.2, and herd-sire interaction variances were small (.002). Genetic correlation for somatic cell score was about .55 between lactations 1 and 2 and between lactations 1 and 3 and .65 between lactations 2 and 3. Phenotypic correlation was .20 between lactations 1 and 2, .16 between lactations 1 and 3, and .31 between lactations 2 and 3.
Genetic groups of unknown parents are extended to the multitrait animal model. Computationally feasible mixed model equations are obtained. A strategy to include genetic groups for missing data is proposed. Canonical and triangular transformations can be applied to the multitrait animal model with groups if the transformations can be applied to the same model without groups. Formulations for REML estimation with groups are derived, and the results are almost as feasible as REML estimation without groups. A numerical example is given to illustrate computations of REML formulations.
Genetic evaluation using animal model with relationship grouping has been shown to be feasible. However, algorithms were unavailable for prediction error variance and REML estimation of variance components. This paper shows that prediction error variance of an estimable function of the total merit of additive genetic and group effects is a simple function of a generalized inverse of the coefficient matrix for a transformed mixed model equation or of the inverse of the coefficient matrix when it is restricted to full rank. The REML algorithms, using the transformed equation, having slightly more complicated expressions than usual but could be more feasible computationally. Formulae for prediction error variance apply in general. The REML algorithms are extended to an animal model with an arbitrary number of random factors and can be extended to estimate covariance components.
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.
A strategy of multi-step minimal conditional regression analysis has been developed to determine the existence of statistical testing and parameter estimation for a quantitative trait locus (QTL) that are unaffected by linked QTLs. The estimation of marker-QTL recombination frequency needs to consider only three cases: 1) the chromosome has only one QTL, 2) one side of the target QTL has one or more QTLs, and 3) either side of the target QTL has one or more QTLs. Analytical formula was derived to estimate marker-QTL recombination frequency for each of the three cases. The formula involves two flanking markers for case 1), two flanking markers plus a conditional marker for case 2), and two flanking markers plus two conditional markers for case 3). Each QTL variance and effect, and the total QTL variance were also estimated using analytical formulae. Simulation data show that the formulae for estimating marker-QTL recombination frequency could be a useful statistical tool for fine QTL mapping. With 1,000 observations, a QTL could be mapped to a narrow chromosome region of 1.5 cM if no linked QTL is present, and to a 2.8 cM chromosome region if either side of the target QTL has at least one linked QTL.