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Biomedical subjects

J P Gibson

Publications and source records attributed to J P Gibson.

At least 19 recordsLinked to original sources

Combination of multiple microsatellite data sets to investigate genetic diversity and admixture of domestic cattle.

Microsatellite markers are commonly used for population genetic analyses of livestock. However, up to now, combinations of microsatellite data sets or comparison of population genetic parameters from different studies and breeds has proven difficult. Often different genotyping methods have been employed, preventing standardization of microsatellite allele calling. In other cases different sets of markers have been genotyped, providing differing estimates of population genetic parameters. Here, we address these issues and illustrate a general two-step regression approach in cattle using three different sets of microsatellite data, to combine population genetics estimates of diversity and admixture. This regression-based method is independent of the loci genotyped but requires common breeds in the data sets. We show that combining microsatellite data sets can provide new insights on the origin and geographical distribution of genetic diversity and admixture in cattle, which will facilitate global management of this livestock species.

Animals↗

Genetic variation in resistance to repeated infections with Heligmosomoides polygyrus bakeri, in inbred mouse strains selected for the mouse genome project.

Since the publication of the mouse genome, attention has focused on the strains that were selected for sequencing. In this paper we report the results of experiments that characterized the response to infection with the murine gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J, C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well-characterized CBA (poor responder) and SWR (strong responder) as our controls. We employed the repeated infection protocol (consisting of 7 superimposed doses of 125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and 6 and assessment of worm burdens in week 6) that was used successfully to identify quantitative trait loci for genes involved in resistance to H. polygyrus. SWR, SJL and NIH mice performed indistinguishably and are confirmed as strong responder strains to H. polygyrus. CBA, C3H and A/J mice all tolerated heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J and BALB/c mice performed variably between experiments, some tolerating heavy worm burdens comparable to those in poor responders, and some showing evidence of resistance, although only in one experiment with female 129/J females and one with female BALB/c was the pattern and extent of worm loss much like that in SWR mice. Because the genetic relationships between six of the strains exploited in this study are now well-understood, our results should enable analysis through single nucleotide polymorphisms and thereby provide more insight into the role of the genes that control resistance to H. polygyrus.

Animals↗

Use of molecular markers to enhance resistance of livestock to disease: a global approach.

The improvement and utilisation of host genetic resistance to disease is an attractive option as a component of livestock disease control in a wide range of situations. This paper reviews the situations where genetic resistance of the host is likely to be a useful component of disease control and provides a framework for deciding whether genetic improvement of resistance is likely to be worthwhile. Discussion is focused on low-input production systems in the developing world, where disease resistance is particularly important. The authors propose an integrated strategy for the use of molecular markers in assessing genetic diversity and in utilising and improving host genetic resistance to disease. The integrated approach assures that there is value in the molecular genetic information whether or not it proves useful in genetic selection, a feature that should prove attractive to funding and executing agencies.

Animals↗

No detectable association of the ESR PvuII mutation with sow productivity in a Meishan x Large White F2 population.

The polymorphism at the PvuII recognition site in the ESR gene showed no statistically significant association with sow productivity traits in a Meishan x Large White F2 population. Estimates of the effect on litter size were, however, in the opposite direction and statistically different from previously published estimates. Taken together with results from other publications, results here indicate that this PvuII polymorphism displays different degrees of linkage disequilibrium with a gene or genes controlling litter size in different populations.

Animals↗

Detection of QTL for milk production on Chromosomes 1 and 6 of Holstein cattle.

Seventy to 75 sons of each of six Holstein sires were assayed for genotypes at a number of microsatellite loci spanning Chromosomes (Chrs) 1 and 6. The number of informative loci varied from three to eight on each chromosome in different sire families. Linkage order and map distance for microsatellite loci were estimated using CRI-MAP. Estimates of QTL effect and location were made by using a least squares interval mapping approach based on daughter yield deviations of sons for 305-d milk, fat, protein yield, and fat and protein percentage. Thresholds for statistical significance of QTL effects were determined from interval mapping of 10,000 random permutations of the data across the bull sire families and within each sire family separately. Across-sire analyses indicated a significant QTL for fat and protein yield, and fat percentage on Chr 1, and QTL effects on milk yield and protein percentage that might represent one or two QTL on Chr 6. Analyses within each sire family indicated significant QTL effects in five sire families, with one sire possibly being heterozygous for two QTLs. Statistically significant estimates of QTL effects on breeding value ranged from 340 to 640 kg of milk, from 15.6 to 28.4 kg of fat, and 14.4 to 17.6 kg of protein.

Alleles↗

Multi-primer target PCR for rapid identification of bovine DRB3 alleles.

Multi-primer target polymerase chain reaction (MPT-PCR) is a rapid method for the identification of specific BoLA-DRB3 alleles. In a single PCR reaction, the presence of two alleles associated with increased risk, DRB3.2*23 (DRB3*2701-2703, 2705-2707) and decreased risk, DRB3.2*16 (DRB3*1501, 1502), of mastitis in Canadian Holstein can be detected. Two outer primers amplify exon 2 of DRB3. Simultaneously, two inner, allele-specific primers amplify individual alleles. Initially, 40 cows previously typed by PCR-restriction fragment length polymorphism (PCR-RFLP) were genotyped using the multi-primer approach. An additional 30 cows were first genotyped by multi-primer target PCR, then by PCR-RFLP. All animals were correctly identified and there were no false positives. This technique can readily be modified to identify other BoLA alleles of interest.

Alleles↗

Quantitative trait loci for upper thermal tolerance in outbred strains of rainbow trout (Oncorhynchus mykiss).

The expression of three putative QTL for upper thermal tolerance (UTT) was examined in two strains of outbred rainbow trout unselected for this trait using simple-sequence repeat (SSR; microsatellite) markers associated with UTT in backcrosses of lines selected on this trait. Two-way diallel lots in the third generation of an outbred pedigree were exposed to an acute thermal challenge. QTL detection was performed separately by each second-generation parent within each diallel lot, incorporating the effects of full sib families and correlated traits. Inheritance of different alleles at the SSR Ssa20.19NUIG from the sire 93-32-1 was strongly associated with the thermal tolerance of his half sib progeny, explaining 7.5% of their phenotypic variance in this trait. A hierarchical linear model incorporating allelic inheritance from all four grandsires of the experimental diallels (in addition to family specific and covariate trait effects) was also used to detect associations between the SSR and thermal tolerance in their third-generation grandprogeny. Ssa20.19NUIG was strongly associated with thermal tolerance in the grandprogeny of the grandsire G(0)SVM2. The generally stronger marker-trait associations found in male parents may be partially due to reduced chromosomal recombination rates in male salmonids compared to females. These results indicate the effects of a QTL on a fitness-related trait in unselected populations of rainbow trout.

Alleles↗

The porcine gonadotropin-releasing hormone receptor gene (GNRHR): genomic organization, polymorphisms, and association with the number of corpora lutea.

The interaction of gonadotropin-releasing hormone (GNRH) and its receptor (GNRHR) is critical in the endocrine regulation of reproduction. The gene (GNRHR) encoding the receptor has been mapped to porcine chromosome 8. There is evidence for three quantitative trait loci (QTL) influencing ovulation rate on this chromosome. We obtained an almost complete sequence (3993 bp, excluding intron 1) of the porcine GNRHR gene using PCR-based comparative genomic walking and inverse genomic walking approaches. Twelve polymorphisms were detected by sequencing of pooled DNA of Chinese Taihu and European Large White pigs, including 7 base substitutions and 5 insertions-deletions (indels). A F2 population of Meishan x European Large White pigs was genotyped for a TG indel in the promoter region, and a C/G substitution in the 3' UTR (untranslated region). A significant association of the C/G substitution with number of corpora lutea at first parity was observed.

3' Untranslated Regions↗

Detection of quantitative trait loci affecting milk production traits on 10 chromosomes in Holstein cattle.

Sons (n = 71 to 75) of each of six Holstein sires were genotyped at 69 microsatellite loci covering a total of 676 cM on chromosomes 3, 5, 9, 10, 13, 15, 17, 20, 23, and 26. Estimates of quantitative trait loci (QTL) effect and location were made using a least squares interval mapping approach based on daughter yield deviations of sons for 305 d milk, fat, and protein yield and fat and protein percentage. Thresholds for statistical significance of QTL effects were determined from interval mapping of 10,000 random permutations of the data across the bull sire families and within each sire family separately. Analyses combining data across sires indicated the presence of QTL affecting milk, fat, and protein yield on chromosomes 20 and 26 and a QTL affecting fat and protein percentage on chromosome 3. Analyses within each sire family separately indicated the presence of segregating QTL in at least one family on 7 of the 10 chromosomes. Statistically significant estimates of QTL effects on breeding value ranged from 438 to 658 kg of milk, from 17.4 to 24.9 kg of fat, 13.0 to 17.0 kg of protein, 0.04 to 0.17% fat, and 0.07 to 0.10% protein.

Animals↗

Bayesian segregation analysis of somatic cell scores of Ontario Holstein cattle.

Bayesian segregation analysis using a Gibbs sampling approach was applied to four sets of simulated data and one set of field data to detect evidence of major genes affecting the evaluated trait. The substitution effect of a major gene and its allelic frequency were estimated for each set of data. For two datasets simulated with a model with no major gene effect, the resulting estimates of polygenic variance and heritability agreed with the simulated values and tests for the presence of a major gene were not significant. Analyses of two sets of data simulated with a major gene produced posterior distributions that gave significant evidence of major gene effects but underestimated the substitution values of the major gene. The segregation analysis of field data suggested that a major gene significantly affected somatic cell score (SCS) in the population of Ontario Holstein cattle. The estimated heritability of SCS was approximately 0.16. The major gene variance accounted for about 17% of the total genetic variance and the point estimate of the frequency of the allele having a positive effect on SCS was 0.30. However, the precision of these estimates is questionable based on the simulation results. The effect of the major gene may be underestimated.

Animals↗

Bi-PASA genotyping of a new polymorphism in the APOB gene shows no evidence for an association with fatness in pigs.

Sequence analysis of PCR products of a 343-bp fragment from exon 29 of the porcine APOB gene of four Erhualian and four Landrace pigs revealed a missense G/C substitution at position of 6117 in this gene. Two allele-specific primers were designed to genotype this polymorphism using the Bi-PASA technique. Genotyping of 146 animals from Erhualian, Hampshire, Large White, Landrace and Duroc breeds revealed large breed differences in allele frequency. No association with fatness was observed within each of the four European breeds, where animals had been selected to be those with the highest and those with the lowest backfat depth at 100 kg liveweight from a large carcass dissection project.

Animals↗

The effect of using different culling regimens on genetic response with two-trait, two-stage selection in a nucleus broiler stock.

Stochastic simulation was used to study the effect on genetic response and inbreeding of various two-stage two-trait culling strategies. Four different parameter sets were considered for the two traits, BW and egg number. Selection of replacement animals was based on animal model best linear unbiased prediction (BLUP) to obtain estimated breeding values (EBV) at the second stage. Culling at Stage 1 was based on either animal model BLUP or phenotypes, and information from culled animals was either available or not available for calculation of second stage EBV. Besides founder individuals, six discrete generations were considered. Culling based on BLUP of two traits at Stage 1 produced higher response than culling on phenotypic evaluations. It was found that culling based on phenotypic evaluation and not carrying information to the second stage reduce rates of response by 9 to 17% and produced inbreeding higher than or close to that of BLUP selection. This study clearly shows that a double penalty of less response and higher inbreeding is generally paid for not using all information. Optimum selection schemes will depend on relative costs and benefits of collecting and processing the extra information required for full BLUP selection schemes.

Animals↗

Using recent versus complete pedigree data in genetic evaluation of a closed nucleus broiler line.

Stochastic simulation was used to study the effect of using full data and pedigree structure vs more recent data and pedigree structure to obtain best linear unbiased predictors (BLUP) of breeding values for single trait selection. Simulations used heritabilities of 0.10 and 0.50, with a population structure of 20 sires each mated to two dams, each producing 10 progeny, with 11 hatches from an unselected base population under both discrete and overlapping generations. Selection of parents was based on BLUP of breeding values using an animal model. The use of the last two generations of data and pedigrees gave the same selection response as when using full data and pedigree structure, for both heritabilities. Under discrete generations with use of only the last generation data and pedigree, which is similar to phenotypic evaluation, response to selection decreased by 21 and 3.8% at Generation 10 compared to selection response when using the full data and pedigree for heritabilities of 0.10 and 0.50, respectively. Corresponding decreases in inbreeding were 72 and 37%. The amount of central processing unit time for genetic evaluation when using the last six, four, and two generations of data and pedigree was reduced to 70, 40, and 11% of that when using the full data set, for a heritability of 0.10 and discrete generations. Very similar values were observed for a heritability of 0.50 and also under overlapping generations.

Animals↗

The tyrosine-17 residue of Nef in SIVsmmPBj14 is required for acute pathogenesis and contributes to replication in macrophages.

The variant simian immunodeficiency virus termed SIVsmmPBj14 induces a rapidly fatal disease in pig-tailed macaques. The acute pathogenic effects of this virus appear to be associated with at least two in vitro characteristics: the ability to induce lymphocyte proliferation; and the ability to replicate in unstimulated PBMC. Two of the amino acids in Nef of PBj14 (the No. 17 residue, tyrosine, and the No. 18 residue, glutamic acid) appear to be linked to the virus' ability to induce lymphocyte activation. To further study the effects of these amino acids on PBj14-induced pathogenesis, we generated two mutant viruses from our molecular clone, PBj6.6, containing either changes in both the No. 17 and No. 18 residues (termed PBj6.6YE-RQ), or a single change in the No. 17 residue (termed PBj6.6Y-R). In vitro analyses of these viruses showed that while their replicative abilities in stimulated peripheral blood mononuclear cells (PBMC) were altered, they still maintained the ability to replicate in unstimulated PBMC. Replication of these viruses in macrophage populations was impaired relative to the wild-type virus. Both mutant viruses were unable to induce proliferation of macaque PBMC in vitro. Virus derived from PBj6.6Y-R was unable to induce acute disease in macaques, but did maintain the ability to induce lymphopenia and intestinal lymphoid hyperplasia. These results show that the tyrosine-17 residue of Nef is linked to lymphocyte proliferation and disease development, but also suggest that the pathogenic characteristics of SIVsmmPBj14 are dependent upon multiple genetic determinants.

Alleles↗

Associations between milk-protein production and reproduction, health, and culling.

Associations between protein production and individual-cow reproductive performance, health, and culling were investigated in a 2-year observational study involving a convenience sample of 75 Ontario, 5 Alberta, and 3 Nova Scotia dairy farms. Protein production was defined by 305-day lactation protein yields and by estimated breeding values for protein yield. After controlling for the level of milk production, herd, parity, breed, and season of calving, there were no significant associations between either measure of protein production and days open or days to first breeding. The only associations between protein production and disease were small positive associations between the estimated breeding value for protein yield and cystic ovaries and mean lactation somatic cell count. The risk of culling, after controlling for the level of milk production, was negatively associated with previous-lactation 305-day protein yield for parity three animals only. The estimated breeding value for protein yield had a small negative association with the overall risk of culling, although the associations were not significant for individual lactations.

Alberta↗

Associations between individual cow factors and milk-protein production.

Associations between stage of lactation, cow characteristics, and protein production were evaluated using data from a 2-year period on 75 Ontario, 5 Alberta, and 3 Nova Scotia dairy farms. Individual-cow protein production was defined by 305-day protein yield and by the estimated breeding value for protein yield. Lactation curves for average daily protein yield were computed by parity, breed, and season of calving. Mean protein yield was highest in early lactation. However, there was no pronounced peak in daily protein yield. Parity was positively associated with 305-day protein yield and negatively associated with the estimated breeding values for protein yield. First-calf heifers had lower protein yields in early lactation and a slower rate of decline in protein yield in late lactation, as compared to later parity cows. Holstein cows had higher unadjusted protein yields and lower protein yields after adjusting for milk yield than other breeds. Holstein cows had significantly higher protein yields early in lactation compared to other breeds, but the rate of decline in protein production in late lactation was also greater. Season was associated with 305-day protein yield; the highest protein yields occurred in cows calving in the fall and winter months, but these cows had the greatest rate of decline in protein production in late lactation.

Animals↗