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A J Teale

Publications and source records attributed to A J Teale.

At least 19 recordsLinked to original sources

Sensitivity of segregation analysis to data structure and transformation: a case study of trypanotolerance in mice.

Sensitivity of segregation analysis for data structure and data transformation was studied using data from two trials in which mice were challenged at three months of age with a cloned isolate of Trypanosoma congolense and survival time was recorded. Data included records from three inbred strains (C57BL/6 (tolerant), A/J, and BALB/c (both susceptible)) and their crosses. Data were standardized and normalized using a modified power transformation. Segregation analysis was applied to both untransformed and transformed data to determine the genetic inheritance of trypanotolerance in these mice. Data from the two trials were analysed separately and combined. Four genetic models were compared; a one locus model, a polygenic model, a mixed model with common variance, and a mixed model with different variances for each major genotype. Even though the separate data sets and the combined data set all supported the hypothesis of a major gene (or a tightly linked cluster of genes) with different variances within each genotype, parameter estimates were highly sensitive to data transformation and several sets of parameter estimates gave similar likelihood values because of high dependency between parameters. Based on the results segregation analysis can be very sensitive to data structure in a crossbreeding design and to data transformation. Interpretation of the results can be misleading if the entire parameter space is not studied carefully.

Animals

Localization of genes controlling resistance to trypanosomiasis in mice.

Tsetse fly-transmitted trypanosomes (Trypanosoma spp.) cause "sleeping sickness' in man and have a serious impact on livestock-based agriculture in large areas of Africa. Multigene control of variation in susceptibility to trypanosomiasis is known to occur in mice, where the C57BI/6 (B6) strain is relatively resistant and the A/J (A) and Balb/c (B) strains are susceptible. Such resistance is also well described among several types of west African cattle. We report here the results of genome-wide scans for genes controlling this trait in the B6 mouse using crosses with two different susceptible strains. Regions on mouse chromosomes 5 and 17 were found to be important in determining resistance in both crosses while an additional region on chromosome 1 showed evidence of involvement in only one cross. We confirmed the size of the effect due to chromosome 17 in F3 intercross populations fixed for alternative parental chromosomes. The three loci are of large effect and account for most of the genetic variation in both F2 populations. We propose that they be designated Tir1, Tir2 and Tir3.

Animals

Polymorphism at the bovine tumor necrosis factor alpha locus and assignment to BTA 23.

We have identified four single-strand conformation variants of the bovine tumor necrosis factor alpha gene by analysis of PCR-amplified fragments. The variants are inherited in Mendelian fashion and are informative for linkage mapping. We have mapped the bovine gene to Chromosome (Chr) 23 in a panel of somatic cell hybrids and observed genetic linkage to the major histocompatibility complex (BoLA) genes and microsatellite markers on bovine Chr 23 in an international bovine reference family panel. The distribution of the alleles was determined in cattle of different breeds and of different geographical origins, which included trypano-susceptible and trypano-tolerant cattle.

Animals

Genetic control of resistance to trypanosomiasis.

To map the genetic sources of trypanotolerance in mice, a linkage analysis of survival following trypanosome challenge was performed by selective genotyping in a large F2 population produced by crossing the resistant C57BL/6 and susceptible BALB/c inbred mouse lines. We report evidence of a chromosomal region of large effect, possibly comprising more than one resistance locus, on Chromosome 17; and of further loci on Chromosomes 1 and 5. Together, these genes can account for all of the difference between the mean parental phenotypes.

Animals

Parasite strain specificity of bovine cytotoxic T cell responses to Theileria parva is determined primarily by immunodominance.

The parasite strain specificity of CTL responses to Theileria parva varies among cattle immunized with the same parasite stock. We have investigated the influence of class I MHC on the strain specificity of CTL responses to T. parva in 19 cattle of defined class I phenotype immunized with either of two T. parva populations, in which protection to subsequent reciprocal challenge correlated with CTL strain specificity. In the majority of animals the response was restricted by the products of one MHC haplotype and there was a consistent bias to some haplotypes in preference to others. In 10 of 13 cattle expressing the molecularly defined MHC specificities A10 and KN104 on one haplotype, the CTL response was restricted entirely by this haplotype, thus allowing a precise analysis of the MHC restriction specificities. The MHC restriction specificity and the parasite population used for immunization both influenced the strain specificity of the response. By examining responses in identical twins immunized with different parasites or in animals before and after challenge with heterologous parasites, animals that mounted a strain-specific response to primary infection were shown to be capable of responding to Ags shared by the two parasite populations. These findings indicate that the strain specificity of CTL responses to T. parva is not determined primarily by immune response genes that define the inherent capacity to respond, but rather is a consequence of the response in individual animals being biased toward a limited number of immunodominant peptide-MHC determinants.

Animals

A panel of polymorphic bovine, ovine and caprine microsatellite markers.

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.

Animals

A polymorphism in randomly amplified DNA that differentiates the Y chromosomes of Bos indicus and Bos taurus.

A small number of west African Bos taurus cattle breeds, including the N'Dama, constitute a valuable genetic resource by virtue of their ability to remain productive under trypanosomiasis challenge. However, introgression of Bos indicus genes into the trypanotolerant breeds, particularly by introduction of zebu bulls, is a threat to this resource. This work describes the characterization and cloning of a bovine randomly amplified polymorphic DNA (RAPD) that is generated in polymorphic DNA (RAPD) that is generated in polymerase chain reaction (PCR) with the 10 base primer ILO1065 from Bos indicus male templates, but not from B. taurus male templates or female templates of either type. Male-specific sequences with homology to the RAPD also occur in B. taurus breeds. This suggests that the polymorphism may be due to base substitution(s) in an ILO1065 priming site, or insertion/deletion events either affecting priming sites or occurring between sites on the cattle Y chromosome. We have shown that cattle, whether of B. indicus or B. taurus phenotype, which possess a typically B. indicus metaphase Y chromosome on the basis of QFQ banding, have a B. indicus ILO1065-generated genotype. The ILO1065-primed RAPD can be used in a simple dot blot assay as a probe of RAPD-PCR products, to provide a convenient, reliable and effective means of detecting introgression of zebu genes in B. taurus cattle populations.

Africa, Western

MHC class I molecules are an essential cell surface component involved in Theileria parva sporozoite binding to bovine lymphocytes.

The major histocompatibility complex (MHC) class I molecules are ubiquitous cell surface molecules involved in the cell-mediated immune response. We show here, using a number of different, independent approaches, that these proteins are an essential component of the host cell surface receptor involved in Theileria parva sporozoite invasion. Monoclonal antibodies (mAbs) reactive with common determinants on MHC class I molecules and with beta-2 microglobulin inhibited sporozoite entry by specifically preventing the initial binding event. However, in experiments using lymphocytes from heterozygous cattle in which at least four MHC class I gene products are expressed, mAbs which reacted with only one of these products did not inhibit entry. Using a series of bovine deletion mutant cell lines from which one or both MHC class I haplotypes had been lost, sporozoite binding and entry clearly correlated with the level of class I surface expression. While the level of sporozoite entry into cells in which one of the MHC class I haplotypes was lost was only slightly lower than into the parent cells, in a double deletion cell line having less than 5% of the class I expression of the parent cells the level of infection was only 4.3% of that into the parent cells. Furthermore, sporozoite entry into cells from a spontaneously arising mutant cell line exhibiting low levels of class I expression was correspondingly low. Treatment of lymphocytes with IL-2 produced a significant increase in host cell susceptibility and sporozoite entry and this increase correlated with either an increase in the number of target molecules per host cell, or in the binding of bovine MHC class I molecules to the mAbs. In particular, a significant increase in the level of reactivity with mAb W6/32 was observed. Lastly, we show that parasite entry can be competitively inhibited with an isolated sporozoite surface protein, p67. However, p67 binds weakly to lymphocyte surface molecules and initial attempts to use p67 to isolate the relevant host cell molecule(s) have not been successful.

Animals

Randomly primed PCR amplification of pooled DNA reveals polymorphism in a ruminant repetitive DNA sequence which differentiates Bos indicus and B. taurus.

By amplification of pools of DNA representative of different bovine populations with single short oligonucleotide primers of random sequence, we were able rapidly to identify markers which distinguish the two major subspecies of domestic cattle, Bos taurus and B. indicus. One of the marker polymorphisms was found to be in a novel, dispersed DNA sequence which occurs in several ruminant species. The marker will assist in the detection of crossbreeding between Zebu and B. taurus types where this threatens a potentially valuable trypanosomiasis-resistant B. taurus genetic resource in West Africa. In addition, the marker will be useful for exploration of the evolutionary relationships of the major subspecies of domestic cattle. The general approach used to identify population-specific DNA polymorphisms has potentially broad application in definition of species, breeds and populations and will be of generic value in studies of genome evolution.

Animals

Characterization of Zebu cattle breeds in Tanzania using random amplified polymorphic DNA markers.

A total of 141 short primers, of arbitrary nucleotide sequence, were used singly in polymerase chain reactions to amplify DNA fingerprints in pools of DNA representing three Zebu cattle breeds. Two primers, which discriminated between the breed-specific DNA pools were used further to amplify individual pool components in order to establish band frequencies of the amplified fingerprints. One of the primers (ILO 1127) amplified a RAPD fingerprint in 61% of TSZ animals but less than 6% in the other breeds, while another primer (ILO 1065) revealed a DNA sequence common to 89% of the Boran animals and less than 30% in the other two breeds. Bandsharing and mean average percentage difference calculated within and between the three breeds using RAPD fingerprint data showed a higher degree of homogeneity within than across the breeds and indicated measurable divergence between the three breeds. It is concluded that RAPD polymorphisms are useful as genetic markers for cattle breed differentiation.

Animals

Differential in vitro and in vivo expression of MHC class II antigens in bovine lymphocytes infected by Theileria parva.

The expression of major histocompatibility complex class II (MHC II) non-polymorphic antigens detected by four monoclonal antibodies was investigated in Theileria parva-infected and non-infected cloned lymphoid cell lines, bulk cultures, and in peripheral blood mononuclear cells (PBMC) and lymph node cells (LNC) of experimentally infected calves. Compared with non-infected cell lines, both immunofluorescence microscopy and flow cytofluorometry analysis of infected lines of alpha beta T-cell, gamma delta T-cell and B-cell origin revealed high expression of MHC II MHC molecules. After T. parva infection in vitro, three alloreactive T cell clones, three interleukin-2 (IL-2)-dependent cell lines and a concanavalin A (Con A)-stimulated bulk culture all had an increase both in the proportion of MHC II+ cells and in their mean fluorescence intensity. Radioimmunoprecipitation of class II molecules biosynthesized in infected and non-infected cells revealed that they were constitutively produced in infected cells, and were a slightly larger relative mass than the MHC II molecules of uninfected cells. In a study of the serial expression of MHC II antigens in PBMC and LNC of six calves inoculated with a lethal dose of T.parva, MHC II expression by non-parasitized cells peaked at Days 7 (LNC) or 9 (PBMC) following inoculation and, subsequently, MHC II non-expressing parasitized lymphocytes progressively outnumbered MHC II-expressing parasitized cells. In two calves studied in detail, MHC II expression in PBMC and LNC generally, and in T cells particularly, increased during the course of the disease. Finally, among LNC sorted for MHC II expression at 11 and 17 days after parasite inoculation, the proportion of parasitized cells increased markedly in MHC II non-expressing populations and was reduced or increased only slightly in MHC II-expressing populations. These findings indicate that: (1) enhanced MHC II antigen expression by parasitized lymphocytes may be important in the pathogenesis of the lymphoproliferation that characterizes T. parva infection; (2) the in vivo preponderance of MHC II non-expressing over MHC II-expressing T. parva-infected cells may reflect host-mediated destruction or antigenic modulation of parasitized MHC II-expressing cells.

Animals

A polymorphism in the bovine gamma-S-crystallin gene revealed by allele-specific amplification.

A polymorphism was detected in the 3' untranslated region of the bovine gamma-S-crystallin gene by direct sequencing of polymerase chain reaction (PCR) products from genomic DNA of an N'Dama bull and a Boran cow. A set of three PCR primers was designed to detect this difference and thus give allele-specific amplification. The two allele-specific primers differ in length by 20 nucleotides so that the allelic products may be distinguished by simple agarose gel electrophoresis following a single PCR reaction. This provides a simple and rapid assay for this polymorphism.

Alleles

Polymerase chain reaction analysis of mitochondrial DNA polymorphism in N'Dama and Zebu cattle.

A study of polymorphisms of mitochondrial DNA (mtDNA) of West African N'Dama (Bos taurus) and East African Zebu (B. indicus) cattle was carried out to obtain information on maternal phylogenetic relationships between these breeds. A relatively large sample size was made possible by using polymerase chain reaction (PCR) amplification of DNA prepared from small blood samples to generate fragments of two known polymorphic mtDNA regions, one within the gene encoding subunit 5 of NADH dehydrogenase and one encompassing the entire D-loop. This approach allowed us to achieve a higher resolution restriction analysis on mtDNA from more animals than would have been possible by conventional methods. PCR-amplified mtDNA of 58 animals from five populations was examined at 26 restriction sites by 16 enzymes. In this way 154 nucleotides of mtDNA were scanned for polymorphism. Six polymorphic sites were located by this means, five of which were within the D-loop and one of which was within the NADH dehydrogenase 5 gene. None of the polymorphisms observed could be considered typical of breed or type.

Africa, Western

A panel of bovine, ovine and caprine polymorphic microsatellites.

We report a set of six new bovine microsatellite polymorphisms based on (CA)n repeats. They are highly polymorphic and thus represent valuable markers for genome mapping. Four of the six are polymorphic in sheep and two are polymorphic in goats. One, which is polymorphic in cattle and sheep and apparently monomorphic in goats, is X-chromosome specific and has potential value in, for example, sex determination and detection of chimaerism.

Alleles