Biomedical subjects
S P Simpson
Publications and source records attributed to S P Simpson.
Probability of random sire exclusion using microsatellite markers for parentage verification.
Many microsatellite sequences have been described in the bovine genome. Being highly polymorphic these have been suggested as markers for parentage verification and individual identification in cattle. We have evaluated the use of five highly polymorphic microsatellite markers for parentage verification in 14 breeds of cattle in the UK. Three of the microsatellite loci occur within introns in genes: BoLA DRB3, steroid 21-hydroxylase, and the beta subunit of the follicle-stimulating hormone. The other two are anonymous sites ETH131 and HEL6. Results were analysed by a statistical approach that takes in to account deviations from Hardy-Wienberg equilibrium and linkage disequilibrium for multiple loci. The method of determining the probability of random sire exclusion uses observed genotype frequencies instead of allele frequencies. Independently, the markers used have a probability of between 0.72 and 0.62 of identifying a parentage error, while used together the five markers give, on average across breeds, a probability of 0.99 of excluding an incorrect sire.
Description of the effects of a single gene which inhibits the normal metabolic response of newborn lambs to exogenous noradrenaline.
A group of newborn Scottish Blackface lambs previously selected for low cold resistance failed to show the normal metabolic response to subcutaneous injection of exogenous noradrenaline. A subsequent study showed this failure to be due to a single major gene. Further studies on the thermogenic and physiological responses and on the inheritance of the trait, are described here. Two intercross matings between non-responders produced responder lambs indicating that the gene is not recessive. The increases in metabolic rate and rectal temperature after injection of noradrenaline were much greater in responder than in non-responder lambs (P less than 0.001), as were the increases in heart rate and respiration rate (P less than 0.001). Dissected brown adipose tissue from non-responders was apparently normal and indistinguishable from brown adipose tissue from responders. Although there was no apparent effect of the gene on birthweight or survival, survival under normal field conditions may be affected.
Associations between the bovine major histocompatibility complex (BoLA) and milk production in Icelandic dairy cattle.
Associations between BoLA type and milk production were investigated using information from 80 Icelandic cattle from four dairy farms in Iceland. The specificity w6 reduced milk, fat and protein yield. Although w6 has been shown to be associated with increased susceptibility to mastitis, there is no evidence to suggest that the reduced yields here were due to mastitis. The association may be due to increased disease susceptibility or due to a direct effect of BoLA Class I antigens.
The effect of dose and line on immunisation of cattle with lymphoblastoid cells infected with Theileria annulata.
Thirty-one Friesian calves in Morocco susceptible to tropical theileriosis were protected against a lethal sporozoite challenge by prior infection with lymphoblastoid cell lines infected and transformed in vitro by a Moroccan stock of Theileria annulata. The challenge infection of cryopreserved sporozoites killed all four susceptible control calves within 20 days. Four schizont-infected cell cultures at Passage 3 were inoculated at four different doses, 10(8), 10(6), 10(4) and 10(2), into pairs of calves. The recipient animals showed great variation in severity of disease symptoms, which did not show a linear correlation with the cell dose inoculated. The most severe disease symptoms were recorded, prior to challenge, in the 10(2) cell dose recipients; one animal died of acute theileriosis and another had to be treated. One of the four cell lines used was more virulent than the other three. Two years after the completion of this experiment, immunised animals have shown normal productivity traits.
The effect of MHC compatibility between parasite-infected cell line and recipient in immunization against tropical theileriosis.
Lymphoblastoid cell lines, infected and transformed in vitro by a Moroccan stock of Theileria annulata, infected and immunized susceptible taurine cattle, at cell doses of 10(8), 10(6), 10(4) and 10(2), regardless of whether the recipients were BoLA matched or mismatched to the donor cell line. The MHC relationship between the cell line and recipient did affect the severity of the clinical response to cell line immunization which may reflect differences in the specific priming of the immune response. At the highest cell doses the BoLA-mismatched recipients reacted more severely than the BoLA-matched. This study shows that, unlike the closely related parasite T. parva, there is no histocompatibility barrier to immunization using T. annulata-infected cell lines which could be achieved with as few as 10(2) allogeneic infected cells. The role of MHC compatibility between cell line and recipient in the priming of a protective immune response is discussed.
The inheritance of non-response to noradrenaline in newborn Scottish blackface lambs.
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Relationship between the bovine major histocompatibility complex (BoLA), erythrocyte markers and susceptibility to mastitis in Icelandic cattle.
Milk and blood samples were obtained from three Icelandic dairy herds. The herds were monitored regularly for mastitis incidence. Cell counts, adenosine triphosphate (ATP) and antitrypsin levels of the milk samples were recorded. In addition, red cell and BoLA typing were performed on the blood. Although cell counts and ATP levels showed significant associations with mastitis, antitrypsin levels did not. Red blood cell antigens N'2 and S1 and the lymphocyte antigen detected by the monoclonal antibody M7 were associated with low cell counts, whilst BoLA w6 and w6.1 were associated with high cell counts. BoLA w6.2 and w11 showed significant association with high antitrypsin levels. Only ED116 showed a significant association with mastitis.
Plasma pyruvate kinase activity vs creatine kinase activity as an indicator of the porcine stress syndrome.
Plasma pyruvate kinase (PK) and creatine kinase (CK) activities were increased significantly (P less than 0.001 and P less than 0.05, respectively) in homozygote halothane-reacting pigs (nn), compared with those activities in homozygote nonreacting pigs (NN). Pyruvate kinase activity was less variable within groups than was CK activity, allowing more effective discrimination between nn and NN geno-types. The PK and CK activities in plasma increase with age in halothane-reacting pigs and the nonreacting pigs. Enzyme activities in heterozygote (Nn) nonreacting pigs did not differ significantly (P greater than 0.05) from enzyme activities of homozygote (NN) nonreacting pigs. Although PK was better than CK in identifying stress-susceptible pigs, age-related effects and the failure to identify heterozygotes may restrict the use of plasma PK activity as a diagnostic test for the stress syndrome.
Bovine alloreactive cytotoxic cells generated in vitro detect BoLA w6 subgroups.
Alloreactive cytotoxic T cells (CTL) were generated in mixed lymphocyte culture against cells bearing subgroups of BoLA w6, as well as in BoLA w4, w10 and w16. Primary cultures were restimulated at weekly intervals with irradiated stimulator cells and tested in a 51Cr-release assay with target cells derived from Theileria annulata-infected cell lines. Generation of CTL was accelerated in animals that had been previously primed in vivo by skin grafting. CTL were generated that were specific for BoLA w6 subgroups and not w6. With w6.1 the specific killing was significant at the 5% level, and with w6.2, 6.3 and 6.4 it was significant at the 0.1% level. Where CTL were potentially generated against two BoLA-A locus allele products at the same time (i.e. with heterozygous stimulator cells), one of which was a w6 subgroup, there was similar CTL activity against both products when w6.4 and w16 or w6.1 and w4 were the combinations involved. In two generations against w10 and either w6.1 or w6.2 there was significantly more killing of w10-bearing targets than those with the w6 subgroup.
Causal analysis of infant deaths in Hawaii.
Infant mortality among the 34,330 births registered in Hawaii during 1978-1979 was analyzed by means of several methods. Path analysis showed the Apgar score to be the best predictor of mortality, although the effects of birth weight, gestation time and preconceptional and postconceptional factors were all highly significant. Commingling analysis attributed 41% of the deaths to high risk factors recognized from the birth certificate. The infant mortality was lowest in tracts with the highest socioeconomic and health standards, but individual variation in socioeconomic standards was a poor predictor of mortality.
Kinship mapping of multilocus systems.
The linear order of loci in a complex system can be determined by recombination, physical assignment, and correspondence of rare haplotypes with double recombinants. An independent approach is based on the concept of kinship between pairs of loci which gives the apparently correct order for the Rhesus system. Noise due to drift, selection, recent hybridization, and errors of haplotype frequency estimation can be controlled by averaging over populations.
Estimation of haplotype frequencies.
Maximum likelihood estimates of haplotype frequencies in multilocus systems are often zero and so may be genetically inacceptable. Estimation problems are discussed, and preferable estimates are derived.
Estimating the ascertainment probability from the number of ascertainments per proband.
Several methods of estimating the ascertainment probability from the distribution of the number of ascertainments per proband have been presented in the literature. Here these methods are compared. The Skellam often gives the best fit, but there are counter examples. The estimate from a Poisson distribution is generally close to the best solution.
Variation in infant mortality rates among census tracts in Hawaii.
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Complex segregation analysis of the locus for beta-aminoisobutyric acid excretion (BAIB).
High excretion of BAIB is determined by an incompletely recessive gene jointly with other familial factors. The parameters estimated from a Japanese sample are: gene frequency = 0.6, displacement between homozygotes = 2.1 sigma, dominance = 0.2, and polygenic heritability = 0.1. Supplementary tests support this mixed model and (unlike classical analysis) give no evidence of segregation disturbance. Complexity of BAIB inheritance should be allowed for in population comparisons and linkage studies, which can be performed reliably under the mixed model.