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Biomedical subjects

A M Crawford

Publications and source records attributed to A M Crawford.

At least 19 recordsLinked to original sources
PubMed2006

Genomic analysis of Oryctes rhinoceros virus reveals genetic relatedness to Heliothis zea virus 1.

Oryctes rhinoceros virus (OrV) is an unassigned invertebrate dsDNA virus with enveloped and rod-shaped virions. Two cloned PstI fragments, C and D, of OrV DNA have been sequenced, consisting of 19,805 and 17,146 bp, respectively, and comprising about 30% of the OrV genome. For each of the two fragments, 20 open reading frames (ORFs) of 150 nucleotides or greater with no or minimal overlap were predicted. Ten of the predicted 40 ORFs revealed significant similarities to Heliothis zea virus 1 (HzV-1) ORFs, of which five, lef-4, lef-5, pif-2, dnapol and ac81, are homologues of conserved core genes in the family Baculoviridae, and one is homologous to baculovirus rr1. A baculovirus odv-e66 homologue is also present in OrV. Five ORFs encode proteins homologous to cellular thymidylate synthase (TS), patatin-like phospholipase, mitochondrial carrier protein, Ser/Thr protein phosphatase, and serine protease, respectively. TS is phylogenetically related to those of eukarya and nucleo-cytoplasmic large dsDNA viruses. However, the remaining 25 ORFs have poor or no sequence matches with the current databases. Both the gene content of the sequenced fragments and the phylogenetic analyses of the viral DNA polymerase suggest that OrV is most closely related to HzV-1. These findings and the re-evaluation of the relationship of HzV-1 to baculoviruses suggest that a new virus genus, Nudivirus, should be established, containing OrV and HzV-1, which are genetically related to members of the family Baculoviridae.

Animals↗
PubMed2003

The use of genetic modification technologies in the discovery of genes affecting production traits and disease resistance in animals.

Genetic modification technologies, developed initially in laboratory strains of selected bacteria and viruses, are essential tools for understanding the genomes of livestock. These tools allow researchers to: isolate, sequence and characterise any livestock gene; locate genes on chromosomes; follow the inheritance of any gene and/or chromosomal region in any pedigree; detect phenotypic variation due to, or associated with, variation in the DNA sequence of a gene and identify the genetic alteration causing this. Most of the many thousands of genes identified in livestock vary between individuals. Finding the best type of the key genes affecting animal productivity is an exciting and a daunting task. It is only possible with the use of laboratory-based genetic modification techniques. This review will briefly describe the technologies now in use and, using local examples, show how molecular geneticists are using these to help identify genetic alterations and breed healthier or more productive animals. As with any new technology, a new language evolves to describe new products and processes. The new language makes communication easier between participants in the field but more difficult for others to understand the technology. A glossary of terms has therefore been added to this review to help readers less familiar with molecular genetics.

Journal Article↗
PubMed2002

Linkage disequilibrium in domestic sheep.

The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D' were also explored. D' was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D' may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D' to determine the true extent of LD.

Animals↗
PubMed2002

Evaluation of single-nucleotide polymorphisms in CAPN1 for association with meat tenderness in cattle.

Micromolar calcium activated neutral protease (CAPN1) was evaluated as a candidate gene for a quantitative trait locus (QTL) on BTA29 affecting meat tenderness by characterization of nucleotide sequence variation in the gene. Single-nucleotide polymorphisms (SNP) were identified by sequencing all 22 exons and 19 of the 21 introns in two sires (Piedmontese x Angus located at the U.S. Meat Animal Research Center in Clay Center, NE; Jersey x Limousin located at AgResearch in New Zealand) of independent resource populations previously shown to be segregating meat tenderness QTL on BTA29. The majority of the 38 SNP were found in introns or were synonymous substitutions in the coding regions, with two exceptions. Exons 14 and 9 contained SNP that were predicted to alter the protein sequence by the substitution of isoleucine for valine in Domain III of the protein, and alanine for glycine in Domain II of the protein. The resource populations were genotyped for these two SNP in addition to six intronic polymorphisms and two silent substitutions. Analysis of genotypes and shear force values in both populations revealed a difference between paternal CAPN1 alleles in which the allele encoding isoleucine at position 530 and glycine at position 316 associated with decreased meat tenderness (increased shear force values) relative to the allele encoding valine at position 530 and alanine at position 316 (P < 0.05). The association of maternal alleles with meat tenderness phenotypes is consistent with the hypothesis of CAPN1 as the gene underlying the QTL effect in two independent resource populations and presents the possibility of using these markers for selective breeding to reduce the numbers of animals with unfavorable meat tenderness traits.

Alleles↗
PubMed2001

Fluid particle accelerations in fully developed turbulence.

The motion of fluid particles as they are pushed along erratic trajectories by fluctuating pressure gradients is fundamental to transport and mixing in turbulence. It is essential in cloud formation and atmospheric transport, processes in stirred chemical reactors and combustion systems, and in the industrial production of nanoparticles. The concept of particle trajectories has been used successfully to describe mixing and transport in turbulence, but issues of fundamental importance remain unresolved. One such issue is the Heisenberg-Yaglom prediction of fluid particle accelerations, based on the 1941 scaling theory of Kolmogorov. Here we report acceleration measurements using a detector adapted from high-energy physics to track particles in a laboratory water flow at Reynolds numbers up to 63,000. We find that, within experimental errors, Kolmogorov scaling of the acceleration variance is attained at high Reynolds numbers. Our data indicate that the acceleration is an extremely intermittent variable--particles are observed with accelerations of up to 1,500 times the acceleration of gravity (equivalent to 40 times the root mean square acceleration). We find that the acceleration data reflect the anisotropy of the large-scale flow at all Reynolds numbers studied.

Journal Article↗
PubMed2001

Familial predictors of treatment outcome in childhood anxiety disorders.

OBJECTIVE: To determine whether family factors are predictive of outcome in children with anxiety disorders who are receiving cognitive-behavioral treatment. METHOD: Participants were 61 children aged 8 to 12 years (mean = 10.0, SD = 1.4) with Axis I anxiety disorders who had been referred to a large Toronto children's hospital. Parents and children completed measures assessing family functioning, parenting stress, parental frustration, and parental psychopathology before and after treatment. Outcome measures included clinician-rated functioning (Children's Global Assessment Scale) and self- and parent-rated anxiety (Revised Children's Manifest Anxiety Scale). RESULTS: Child ratings of family dysfunction and frustration predicted clinician-rated improvement (total R2 = 0.28, p < .001). Mother and father reports of family dysfunction, and maternal parenting stress, predicted mother-rated child improvement (total R2 = 0.18, p < .01). Father-rated somatization and child reports of family dysfunction and frustration predicted child-rated improvement (total R2 = 0.25, p < .001). Several family factors improved with treatment. CONCLUSION: Family dysfunction appears to be related to less favorable treatment outcome in children with anxiety disorders.

Anxiety Disorders↗
PubMed2001

An enhanced linkage map of the sheep genome comprising more than 1000 loci.

A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) > or = 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of > 20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of > 1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community.

Animals↗
PubMed2001

Weight change and atypical antipsychotic treatment in patients with schizophrenia.

Schizophrenic patients who have been prescribed atypical antipsychotics have a potential risk of gaining weight. The implications of weight gain for clinical care may differ depending on whether a patient is underweight or overweight at baseline. The exact mechanism for weight gain is not known, but several factors have been identified that can help predict which patients are at risk for gaining weight. These factors include better clinical outcome, increased appetite, and low baseline body mass index. In patients treated with olanzapine for up to 3 years, weight gain trended toward a plateau at approximately 36 weeks. Weight gain interventions, including behavioral modifications, show promise in controlling or reducing weight in patients treated with antipsychotics.

Antipsychotic Agents↗
PubMed2001

Superior efficacy of olanzapine over haloperidol: analysis of patients with schizophrenia from a multicenter international trial.

BACKGROUND: Previously, a double-blind, 6-week, parallel-group trial compared the therapeutic profiles of olanzapine (5-20 mg/day; N = 1,336) and haloperidol (5-20 mg/day; N = 660) in 1996 patients with DSM-III-R schizophrenia (83.1%) or schizophreniform (1.9%) or schizoaffective disorders (15.0%) and showed olanzapine to have a superior, broader spectrum of efficacy as well as a more favorable adverse event profile. The present post hoc analysis examined the efficacy of olanzapine compared with haloperidol in the schizophrenic cohort of that study and in subgroups of schizophrenic patients defined by baseline symptom profile and course of illness. METHOD: A total of 1,658 patients were included. Patients were included in analyses of change if they had both a baseline and at least 1 postbaseline measurement (N = 1,622; 1,096 olanzapine-treated patients, 526 haloperidol-treated patients). An analysis of variance was used to compare treatment effects on efficacy measurements including the Brief Psychiatric Rating Scale (BPRS; scored 0-6) and the Positive and Negative Syndrome Scale (total, positive subscale, and negative subscale scores). RESULTS: Olanzapine-treated patients exhibited statistically significantly greater improvements from baseline (last observation carried forward) on all efficacy measurements. Olanzapine-treated patients with predominantly positive, predominantly negative, or mixed symptoms had statistically significantly greater improvements in BPRS total scores compared with similar haloperidol-treated patients. Patients with primarily chronic negative symptoms and patients with chronic or subchronic courses of illness had statistically significantly greater mean improvements from baseline on the BPRS total with olanzapine compared with haloperidol. Furthermore, within the olanzapine treatment group, patients with a subchronic course of illness had greater mean improvements than patients with a chronic course of illness. CONCLUSION: Olanzapine was more effective than haloperidol in treating a varied spectrum of patients with schizophrenia, including patients with positive, negative, or mixed symptom profiles and either a chronic or subchronic course of illness.

Adult↗
PubMed2000

Genetic variation within the Merino sheep breed: analysis of closely related populations using microsatellites.

Genetic relationships among six populations of Merino sheep were investigated using microsatellites. The history of the six populations is relatively well documented, with all being derived from the Spanish Merino breed within the last 400 years. Genetic variation was highest amongst the Spanish and Portuguese populations, although the preservation of genetic diversity within the other populations was high. By a variety of different statistical tests the French Mutton, German Mutton and New Zealand Merino populations could be differentiated from each other and the Iberian Merinos, indicating that microsatellites are able to track relatively recent changes in the population structure of sheep breeds. The dendrograms constructed on the basis of microsatellite allelic frequencies showed that populations that have shared selection criteria (meat vs. wool) tend to cluster together.

Animals↗
PubMed1999

Genetic characterisation of protective vaccine responses in sheep using multi-valent Dichelobacter nodosus vaccines.

Protective vaccine responses to nine distinct serogroups of Dichelobacter nodosus (serogroups A-I) can be readily measured by serogroup-specific K-agglutinating antibody titres. On the basis of a large quantitative genetic experiment (1200 progeny from 129 sire groups), it was shown that variation in antibody responses following vaccination with a multi-valent pilus antigen D. nodosus vaccine (serogroups A-I) is, in part, under genetic control and thus heritable. Based on the genetic relationships between antibody responses to all nine antigens, results suggested that both genes for a broad-based and genes for serogroup-specific response contributed to genetic variation in vaccine response. Furthermore, preliminary data in 389 progeny showed that polymorphism within the ovine major histocompatibility (MHC) based on serological classification accounted for a significant proportion of the variation in vaccine responses. In subsequent experimentation, we examined the importance of genetic polymorphism within the ovine MHC, and the possibility of genes outside the MHC for their involvement in antigen-specific and broad-based vaccine response. Within two large half sib families(131, and 143 progeny), four MHC haplotypes were investigated and found to be associated with differential antibody responses to six out of eight distinct vaccine-antigens presented to the host in a multi-valent vaccine. The model used here shows how well characterised immunogens, quantitative genetic experimentation, and molecular gene mapping tools can be used to unravel genetic differences in host responses to commercial vaccines.

Agglutination Tests↗
PubMed1999

Isolation and mapping of the first ruminant multidrug resistance genes.

The first ruminant multiple drug resistance gene (MDR1) has been cloned and sequenced from sheep. Sequence data revealed the sheep MDR1 gene to have high sequence and structural similarity to other characterized MDR proteins from humans and rodents. A restriction fragment length polymorphism was discovered using the EcoRI enzyme and used to map the MDR1 gene to sheep chromosome 4. Physical mapping using fluorescent in situ hybridisation confirmed this map placement and assigned the MDR1 locus in the region 4q15-q21. The ovine MDR2 gene was also cloned and found to map to the same region as MDR1.

ATP Binding Cassette Transporter, Subfamily B↗