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J N Derr

Publications and source records attributed to J N Derr.

At least 19 recordsLinked to original sources

Bison PRNP genotyping and potential association with Brucella spp. seroprevalence.

The implication that host cellular prion protein (PrP(C)) may function as a cell surface receptor and/or portal protein for Brucella abortus in mice prompted an evaluation of nucleotide and amino acid variation within exon 3 of the prion protein gene (PRNP) for six US bison populations. A non-synonymous single nucleotide polymorphism (T50C), resulting in the predicted amino acid replacement M17T (Met --> Thr), was identified in each population. To date, no variation (T50; Met) has been detected at the corresponding exon 3 nucleotide and/or amino acid position for domestic cattle. Notably, 80% (20 of 25) of the Yellowstone National Park bison possessing the C/C genotype were Brucella spp. seropositive, representing a significant (P = 0.021) association between seropositivity and the C/C genotypic class. Moreover, significant differences in the distribution of PRNP exon 3 alleles and genotypes were detected between Yellowstone National Park bison and three bison populations that were either founded from seronegative stock or previously subjected to test-and-slaughter management to eradicate brucellosis. Unlike domestic cattle, no indel polymorphisms were detected within the corresponding regions of the putative bison PRNP promoter, intron 1, octapeptide repeat region or 3'-untranslated region for any population examined. This study provides the first evidence of a potential association between nucleotide variation within PRNP exon 3 and the presence of Brucella spp. antibodies in bison, implicating PrP(C) in the natural resistance of bison to brucellosis infection.

Age Factors↗

Development of a linkage map and QTL scan for growth traits in North American bison.

PCR protocols incorporating fluorescently labeled multiplexed primer combinations were developed to produce a linkage map for bison. Three hundred fifty eight microsatellite loci spanning all 29 autosomes were genotyped via 83 PCR multiplexes and nine individual amplifications. A total of 292 markers were integrated into an autosomal linkage map for bison. The sex averaged bison map (2,647 cM) was approximately 9% longer than the corresponding USDA MARC map, which covered 2,415 cM. Utilizing weaning, yearling and 17-month weights from two private bison herds, a QTL scan was conducted using the developed linkage map. LOD peaks suggestive of QTL were identified on chromosomes 2, 7, 15, and 24 for weaning weight, chromosomes 4, 14, and 15 for yearling weight and chromosomes 8, 14, and 25 for 17-month weight. Four of the identified chromosomes have conserved synteny with regions harboring growth QTL in cattle.

Animals↗

Identification of a novel ovine PrP polymorphism and scrapie-resistant genotypes for St. Croix White and a related composite breed.

Susceptibility to scrapie is primarily controlled by polymorphisms in the ovine prion protein gene (PRNP). Here, we report a novel ovine exon three PRNP polymorphism (SNP G346C; P116), its association with the ovine ARQ allele (P116A136R154Q171), and two new genotypes (PARQ/ARR; PARQ/ARQ) for the St. Croix White (SCW) breed and a related composite (CMP) breed developed for meat production. The (P116) polymorphism occurs between the N-terminal cleavage site and the hydrophobic region of the ovine prion protein, a region which exhibits extreme conservation across mammalian taxa. The relatively high frequency (0.75) of resistant ARR alleles and the absence of ARQ alleles for the SCW ewes used as breeding stock for CMP resulted in significant genic differentiation (P = 0.0123; S.E. = 0.00113). Additionally, the majority of the SCW (66.7%) and CMP (65.4%) sampled possessed genotypes considered resistant or nearly resistant to scrapie and experimental BSE (bovine spongiform encephalopathy.

Alleles↗

Genetic diversity among Canadienne, Brown Swiss, Holstein, and Jersey cattle of Canada based on 15 bovine microsatellite markers.

The genetic diversity among Canadienne, Brown Swiss, Holstein, and Jersey cattle was estimated from relationships determined by genotyping 20 distantly related animals in each breed for 15 microsatellites located on separate chromosomes. The Canadienne, Holstein, and Jersey cattle had an average of six alleles per loci compared with five alleles for Brown Swiss. Furthermore, a number of potentially breed-specific alleles were identified. The allele size variance among breeds was similar, but varied considerably among loci. All of the loci studied were equally heterozygous, as were Brown Swiss, Canadienne, and Holstein cattle (0.68-0.69) whereas Jersey cattle showed lower heterozygosity (0.59). The within-breed estimates of genetic distance were greater than zero and significant. The genetic distance between Canadienne and Holstein (0.156), Brown Swiss (0.243), and Jersey (0.235) was negligible, suggesting close relationship. Concurrently, Brown Swiss and Holstein (0.211) cattle also demonstrated close relationship. In contrast, the Jersey breed was genetically distant from the Brown Swiss and Holstein cattle (0.427 and 0.320, respectively). The characterization of Canadienne cattle, as part of the genetic resource conservation effort currently underway in Canada, underscores the difficulty in scientifically establishing unique breeds. Therefore, the need to consider all relevant morphological characteristics and production performance in combination with available cultural, historical, pedigree, and molecular information becomes relevant when identifying breeds for conservation.

Alleles↗

Differential introgression of uniparentally inherited markers in bison populations with hybrid ancestries.

Historical hybridization between Bison bison (bison) and Bos taurus (cattle) has been well documented and resulted in cattle mitochondrial DNA (mtDNA) introgression, previously identified in six different bison populations. In order to examine Y chromosome introgression, a microsatellite marker (BYM-1) with non-overlapping allele size distributions in bison and cattle was isolated from a bacterial artificial chromosome (BAC) clone, and was physically assigned to the Y chromosome by fluorescence in situ hybridization. BYM-1 genotypes for a sample of 143 male bison from 10 populations, including all six populations where cattle mtDNA haplotypes were previously identified, indicated that cattle Y chromosome introgression had not occurred in these bison populations. The differential permeability of uniparentally inherited markers to introgression is consistent with observations of sterility among first generation hybrid males and a sexual asymmetry in the direction of hybridization favouring matings between male bison and female cattle.

Animals↗

Historical population size change of bowhead whales inferred from DNA sequence polymorphism data.

Nucleotide sequence data from the mitochondrial control region were used from a phylogenetic context to investigate the long-term history of a population of bowhead whales (Balaena mysticetus). In addition, the coalescence time of these sequences was used to estimate the age of the inferred patterns of population size change. The results indicate that mitochondrial genetic polymorphism was not affected by a recent bottleneck that occurred near the turn of the 20th century, thereby preserving the signature of historical population size change in the mitochondrial genome. Further analysis showed that this population underwent an expansion initiated in the Middle to Late Pleistocene. As such, early Holocene changes in Arctic sea ice distribution appear to have had little influence on patterns of genetic variability in this population.

Animals↗

Validation of 15 microsatellites for parentage testing in North American bison, Bison bison and domestic cattle.

Fifteen bovine microsatellites were evaluated for use in parentage testing in 725 bison from 14 public populations, 178 bison from two private ranches and 107 domestic cattle from five different breeds. The number of alleles per locus ranged from five to 16 in bison and from five to 13 in cattle. On average, expected heterozygosity, polymorphism information content (PIC) and probability of exclusion values were slightly lower in bison than in cattle. A core set of 12 loci was further refined to produce a set of multiplexed markers suitable for routine parentage testing. Assuming one known parent, the core set of markers provides exclusion probabilities in bison of 0.9955 and in cattle of 0.9995 averaged across all populations or breeds tested. Tests of Hardy-Weinberg and linkage equilibrium showed only minor deviations. This core set of 12 loci represent a powerful and efficient method for determining parentage in North American bison and domestic cattle.

Animals↗

mtDNA affinities of the peoples of North-Central Mexico.

mtDNA haplotypes of representatives of the cosmopolitan peoples of north-central Mexico were studied. Two hundred twenty-three samples from individuals residing in vicinities of two localities in north-central Mexico were analyzed. A combination of strategies was employed to identify the origin of each haplotype, including length variation analysis of the COII and tRNALYS intergenic region, nucleotide sequence analysis of control region hypervariable segment 1, and RFLP analysis of PCR products spanning diagnostic sites. Analysis of these data revealed that the majority of the mtDNA haplotypes were of Native American origin, belonging to one of four primary Native American haplogroups. Others were of European or African origin, and the frequency of African haplotypes was equivalent to that of haplotypes of European derivation. These results provide diagnostic, discrete character, molecular genetic evidence that, together with results of previous studies of classical genetic systems, is informative with regard to both the magnitude of African admixture and the relative maternal contribution of African, European, and Native American peoples to the genetic heritage of Mexico. Phylogenetic analysis revealed that African sequences formed a basal, paraphyletic group.

Africa↗

Evaluating a putative bottleneck in a population of bowhead whales from patterns of microsatellite diversity and genetic disequilibria.

A size-selected Balaena mysticetus genomic library was screened for clones containing simple sequence repeat, or microsatellite, loci. A total of 11 novel loci was identified. These loci were combined with a set of 9 published loci, for a total of 20 markers, and were scored across a sample of 108 bowhead whales from the Bering-Chukchi-Beaufort Seas population of bowhead whales. Genetic variability was measured in terms of polymorphism information content values and unbiased heterozygosity. From the latter, estimates of long-term effective population size were obtained. In addition, gametic phase disequilibrium among loci was investigated. Moderate to high levels of polymorphism were found overall, and the long-term effective size estimates were large relative to total population size. Tests of heterozygosity excess (Cornuet and Luikart 1996) and allele frequency distribution (Luikart et al. 1998) indicated that the possibility of a recent genetic bottleneck in the Bering-Chukchi-Beaufort Seas population of bowhead whales is highly unlikely. However, the fact that five loci displayed a statistically significant heterozygote deficiency remains to be explained.

Animals↗

Nucleotide sequence evolution at the kappa-casein locus: evidence for positive selection within the family Bovidae.

Kappa-casein is a mammalian milk protein involved in a number of important physiological processes. In the gut, the ingested protein is split into an insoluble peptide (para kappa-casein) and a soluble hydrophilic glycopeptide (caseinomacropeptide). Caseinomacropeptide is responsible for increased efficiency of digestion, prevention of neonate hypersensitivity to ingested proteins, and inhibition of gastric pathogens. Variation within this peptide has significant effects associated with important traits such as milk production. The nucleotide sequences for regions of kappa-casein exon and intron four were determined for representatives of the artiodactyl family Bovidae. The pattern of nucleotide substitution in kappa-casein sequences for distantly related bovid taxa demonstrates that positive selection has accelerated their divergence at the amino acid sequence level. This selection has differentially influenced the molecular evolution of the two kappa-casein split peptides and is focused within a 34-codon region of caseinomacropeptide.

Animals↗

Genetic characterization of the bovine leukaemia inhibitory factor (LIF) gene: isolation and sequencing, chromosome assignment and microsatellite analysis.

The bovine leukaemia inhibitory factor was isolated from a phage library and sequences for the gene, in addition to 1213 bp of 5' and 432 bp of 3' sequences, were obtained and compared with other mammalian leukaemia inhibitory factor genes. Comparisons indicated amino acid homologies ranging from 89.6% to 77.2% with the human and mouse homologues, respectively. Analysis of 500 bp of 5' regulatory regions indicated homologies ranging from 83.6% to 74.4% with the corresponding human and sheep sequences, respectively. Additionally, bovine leukaemia inhibitory factor-specific primers were prepared, and a panel of bovine x hamster somatic cell lines were analysed by the polymerase chain reaction (PCR). Data indicated 93% concordance of leukaemia inhibitory factor with aldehyde dehydrogenase 2 located on bovine chromosome 17, and concordance of 81% with myelin basic protein situated on bovine chromosome 24. Southern analysis of selected hybrids confirmed the PCR results, thus conclusively assigning the bovine leukaemia inhibitory factor gene to chromosome 17. Sequence analysis also revealed a microsatellite in intron 2 of the bovine leukaemia inhibitory factor. Analysis of this region by PCR in 22 unrelated Bos taurus and 19 unrelated Bos indicus cattle detected nine different alleles. Polymorphic information content values were 0.53 and 0.80 in B. taurus and B. indicus, respectively. Additionally, the same leukaemia inhibitory factor primers successfully detected allelic variants at this locus in Bos javanicus, Bos guarus and Bison bison but not in Odocoileus virginianus.

Amino Acid Sequence↗

Dietary modulation of rat colonic cAMP-dependent protein kinase activity.

Malignant transformation of cells is associated with enhanced proliferation and alterations in cAMP-dependent protein kinase (PKA) activity. To investigate the role of PKA in normal colonic cell proliferation, PKA was characterized in rat colonic mucosa. In addition, rats were fed diets containing different fats (corn oil, fish oil) and fibers (pectin, cellulose, fiber free) to elicit varying levels of colonic cell proliferation in order to study this signaling system under normal physiologic conditions. Overall, PKA activities were higher in cytosolic compared to membrane fractions. PKA type II (PKA II) isozyme contributed 89 +/- 1% and 96 +/- 1% of total PKA activity in cytosolic and membrane fractions, respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of mRNA for both the alpha and beta isoforms of the regulatory subunits of PKA II. PKA activities were 21-33% higher in distal membrane and total distal fractions in rats fed a cellulose/corn oil diet compared to animals consuming the other fiber/fat diets. These effects were seen only in the distal colon, where the number of cells per crypt column was elevated only in animals fed the cellulose/corn oil diet relative to other diets. Diet-induced mitogenic responses did not involve significant changes in the relative activity of PKA I and II isozymes. These data demonstrate that dietary effects on PKA activity in the distal colon may be related to changes in cell differentiation as indicated by the number of cells per crypt column.

Animals↗

Protein kinase C isoforms in human and rat colonic mucosa.

The protein kinase C (PKC) family of enzymes plays a key role in the regulation of cellular events, including cell proliferation and differentiation. Work from our laboratory has shown that the effects of dietary fat and fiber on colonic cell proliferation were positively correlated with membrane/cytosol PKC activity ratios (Chapkin et al., 1993, J. Nutr. 123, 649-655). The presence and subcellular distribution of specific PKC isoforms in rat and human colon were therefore determined in cytosolic and membrane extracts. Tissue extracts were probed with antibodies to individual PKC isoforms. PKC alpha, beta, delta, epsilon, and zeta were detected in both rat and human colonic mucosa, while PKC eta was detected in human colonic mucosa only. PKC alpha, beta, and zeta were predominantly localized in the cytosolic fraction, whereas the majority of PKC delta, epsilon, and eta were found in the membrane-associated fraction. Presence of mRNA for individual PKC isoforms was determined by reverse transcriptase PCR (RT-PCR). Using rat colonic mucosa, mRNA for PKC alpha, beta, delta, epsilon, eta, and zeta were detected by RT-PCR with identity confirmed by sequencing. The relative steady-state levels of PKC isoforms in human colon adenocarcinoma as compared with normal colonic mucosa were determined, with adenocarcinomas having higher amounts of cytosolic PKC beta, delta, epsilon, eta, and zeta. PKC isoforms were also detected in viable, exfoliated colonic cells isolated from human feces, demonstrating that this noninvasive method can be utilized to examine PKC expression in colonic cells. These results demonstrate that colonic mucosa expresses both calcium-dependent (classical) and calcium-independent (novel and atypical) PKC isoforms with distinct subcellular distributions for each. The dynamics of these PKC isoforms may have implications in the development of colon carcinogenesis.

Adenocarcinoma↗

Further flow cytometric studies of the effects of triethylenemelamine on somatic and testicular tissues of the rat.

Exposure to the mutagen triethylenemelamine on rat bone marrow, blood, and testis was studied using flow cytometry of DAPI-stained nuclei. Increased coefficients of variation (CVs) of the G1 peaks were observed in bone marrow and blood after both 1 d and 5 d exposures. After 5 d exposure and 7 d recovery both tissues had recovered, in some cases to significantly lower CVs. Increased CVs of the 1C peak of testis were observed only after 5 d exposure to the high dose with no subsequently observed recovery. Bone marrow cells also were stained with Hoechst 33258 and Propidium Iodide. No differences among dyes were observed indicating that increased CVs likely are due to DNA damage resulting from interactions with the mutagen rather than differences in how the dyes bind to DNA relative to mutagen binding. This study demonstrates that differences occur among tissues in how quickly they respond and recover from mutagen exposure. Increased CVs, cell cycle alterations, and decreased CVs after recovery are all potentially useful biomarkers of effect for laboratory and field studies in environmental toxicology.

Animals↗