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Biomedical subjects

D J Hetzel

Publications and source records attributed to D J Hetzel.

At least 19 recordsLinked to original sources

Genetic diversity of Asian water buffalo (Bubalus bubalis): mitochondrial DNA D-loop and cytochrome b sequence variation.

Swamp and river buffalo mitochondrial DNA (mtDNA) was sequenced for 303 bp of the cytochrome b gene for 54 animals from 14 populations, and for 158 bp of the D-loop region for 80 animals from 11 populations. Only one cytochrome b haplotype was found in river buffalo. Of the four haplotypes identified in swamp buffalo, one found in all populations is apparently ancestral both to the other swamp haplotypes and to the river haplotype. The phylogenetic relationships among the 33 D-loop haplotypes, with a cluster of 11 found in swamp buffalo only, also support the evolution of domesticated swamp and river buffalo from an ancestral swamp-like animal, most likely represented today by the wild Asian buffalo (Bubalus arnee). The time of divergence of the swamp and river types, estimated from the D-loop data, is 28,000 to 87,000 years ago. We hypothesise that the species originated in mainland south-east Asia, and that it spread north to China and west to the Indian subcontinent, where the rive type evolved and was domesticated. Following domestication in China, the domesticated swamp buffalo spread through two separate routes, through Taiwan and the Philippines to the eastern islands of Borneo and Sulawesi, and south through mainland south-east Asia and then to the western islands of Indonesia.

Animals↗

New markers on bovine chromosome 1 are closely linked to the polled gene in Simmental and Pinzgauer cattle.

In this study, four new markers located on bovine Chromosome 1 were tested for linkage with the polled condition in the Simmental and Pinzgauer breeds. The microsatellites INRA212 (D1S42) and the gene for keratin-associated protein 8 (KAP8) show significant linkage with polled at theta = 0.00 (Lod = 6.92), and theta = 0.033 (Lod = 6. 52) respectively. The microsatellite INRA117 (D1S20) and the gene for interferon-alpha receptor (IFNAR) show maximum Lod scores of 2.1 and 1.8 at a recombination rate of zero.

Animals↗

Evidence for a major gene determining the resistance of Indonesian Thin Tail sheep against Fasciola gigantica.

The genetic basis of the high resistance of Indonesian Thin Tail (ITT) sheep against Fasciola gigantica has been studied by measuring the resistance levels of ITT sheep, St. Croix sheep and their F2 and F3 crossbreds. All of the sheep were bred and reared in the same environment. Approximately half of the F2 and F3 crossbreds were as resistant as the ITT parental breed, one-quarter had the low resistance of the St. Croix parental breed and the rest had an intermediate level of resistance. It is concluded that the high resistance is determined by a major gene with incomplete dominance. The prevalence of the gene in the ITT sheep population is estimated to be about 90%. The resistance may be innate or acquired; but, regardless of the mechanism, it could be used to control fasciolosis caused by F. gigantica by breed substitution or by crossbreeding with other breeds of sheep.

Animals↗

Genetic diversity of Asian water buffalo (Bubalus bubalis): microsatellite variation and a comparison with protein-coding loci.

Twenty-one microsatellite loci in 11 populations of Asian water buffalo (eight swamp, three river type) were analysed and, within and among populations, genetic variability was compared with results from 25 polymorphic protein-coding loci. Within-population mean heterozygosity ranged from 0.380-0.615, approximately twice that estimated from the protein-coding loci (0.184-0.346). Only eight significant departures from Hardy-Weinberg equilibrium (involving four loci) were detected; global tests showed significant heterozygote deficiencies for these four loci. Non-amplifying alleles are likely to be segregating in some or all populations for one of these loci, and probably for the other three. There was significant differentiation between the swamp and river types of water buffalo, and among populations within each buffalo type. Estimates of theta (measure of population differentiation) for each locus for the eight swamp populations were all highly significant (mean theta = 0.168 +/- 0.018). Mean theta for protein-coding loci was not significantly different (0.182 +/- 0.041). The variance among protein-coding loci was significantly higher than among microsatellite loci, suggesting balancing selection affecting allele frequencies at some protein-coding loci. Genetic distances show clear separation of the swamp and river types, which were estimated to have diverged at least 10,000-15,000 years ago. The topology of the swamp populations' microsatellite tree is consistent with their geographical distribution and their presumed spread through south-east Asia. By contrast, the tree based on the protein-coding loci distances is quite different, being clearly distorted by a bottleneck effect in one population, and possibly in at least two others. As many domestic livestock breeds are possibly descended from small numbers of founders, microsatellite-based trees are to be preferred in assessing breed genetic relationships.

Alleles↗

Gestational trophoblastic disease presenting as a large metastasis to the finger.

Cutaneous metastases of gestational trophoblastic disease are extremely uncommon. A patient with metastatic, poor prognosis disease and a large metastatic lesion on her left fifth digit is presented. The clinical course and complete response to EMACO chemotherapy are outlined. The presence of metastatic disease in a reproductive-age woman requires consideration of gestational trophoblastic disease in the differential diagnosis.

Adult↗

The cosmid CSSM25 assigns syntenic group U2 to bovine chromosome 9 and is localized to ovine chromosome 8.

The cosmid-derived microsatellite CSSM 25 has previously been shown to map to bovine syntenic group U2 by linkage and hybrid somatic cell analysis. We have mapped the cosmid by fluorescent in situ hybridization to bovine Chromosome (Chr) 9q17-21 and ovine Chr 8q17-21 and hence assign U2 to Chr 9 in cattle. Bovine Chr 9 and ovine Chr 8 show strong banding pattern homology, and the localization of CSSM 25 to the same region confirms the strong conservation of gene locations on these chromosomes.

Animals↗

A set of polymorphic DNA microsatellites useful in swamp and river buffalo (Bubalus bubalis).

DNA microsatellites have found widespread application in gene mapping, pedigree determination and population genetics. In closely related species such as bovids, heterologous polymerase chain reaction (PCR) primers may in some cases be used, bypassing the need to isolate and characterize microsatellite-containing sequences and design PCR primers. We report on the ability of a set of eighty bovine derived DNA microsatellite primers to amplify sequences in the two types (swamp and river) of water buffalo (Bubalus bubalis). Number of alleles and per cent heterozygosities in a large number of animals were determined on a subset of microsatellite loci selected on the robustness of the primers. These loci will form the basis of a set of polymorphic DNA markers for use in water buffalo.

Alleles↗

Isolation and mapping of a single-locus minisatellite sequence marker to 1q36-qter and synteny group 10 in cattle and to 1q36-qter in sheep.

A minisatellite sequence (RD1613) was isolated from a bovine cosmid genomic library and its chromosomal location determined in cattle and sheep. In cattle, somatic cell hybrid panel analysis assigned RD1613 to the syntenic group U10 with a concordancy of 100%. In situ hybridization placed RD1613 onto bovine chromosome 1 in the region of bands q36-qter. This is the first in situ localization to chromosome 1 in cattle and allows the provisional assignment of syntenic group U10 to this chromosome. It was also found that RD1613 hybridized strongly to sheep genomic DNA. In situ hybridization localized RD1613 to sheep chromosome 1q36-qter, which is consistent with homology between cattle chromosome 1 and sheep chromosome 1q. The RD1613 probe detects a polymorphic single locus marker (designated D1S1) in both cattle and sheep and will be very useful in linkage studies.

Animals↗

Characterization of 65 bovine microsatellites.

Microsatellites or simple sequence repeat (SSR) polymorphisms are used widely in the construction of linkage maps in many species. High levels of polymorphism coupled with the ease of analysis of the polymerase chain reaction (PCR) have resulted in this type of maker being one of the most widely used for genetic analysis. In this paper we describe 58 polymorphic bovine microsatellites that were isolated from insert size selected bovine genomic libraries. Primer sequences, number of alleles, and heterozygosity levels in cattle reference families are reported. Chromosomal locations for 47 of these microsatellites as well as for 7 previously described systems derived from entries in the Genbank or EMBL databases have been determined. The markers map to 24 syntenic or chromosomal locations. Polymorphic bovine microsatellites were estimated to occur, on average, every 320 kb, and there is no evidence of clustering in the genome. Thirty of the bovine-derived microsatellite systems gave specific and polymorphic products in sheep, adding to the number of useful markers in that species.

Animals↗

Genetic markers for the Booroola fecundity (Fec) gene in sheep.

Animals from the Booroola line of Australian Merino sheep are characterized by a high ovulation rate that can be attributed to the presence of a codominant allele (FecB). The specific function of the gene has not been identified. Effective use of the trait within the sheep breeding industry requires one or more genetic markers that can distinguish between alternative alleles at the locus Fec. With a combination of DNA minisatellite markers and polymorphic protein markers, a cluster of seven minisatellite fragments has been identified as being linked to the Fec gene and to the ovine A blood group locus. The minisatellite fragments have been derived from multilocus probes and hence cannot be used to define the chromosomal location of the Fec gene or to serve as diagnostic markers for Fec. The derivation of cloned single locus markers from the minisatellite fragments will enable finer scale mapping of the Fec and the A blood group locus in sheep.

Animals↗

Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.

Adolescent↗

Biochemical genetics of glycogenosis type II in Brahman cattle.

Glycogenosis type II is an inherited lysosomal storage disorder caused by acid alpha-glucosidase deficiency. The disorder is inbred in Brahman cattle, and the incidence of carriers in Australian herds averages 15%. Affected animals are lethargic and die typically in the eighth or ninth month after birth. A complete lack of acid alpha-glucosidase synthesis was demonstrated in cultured fibroblasts and muscle tissue of affected animals. Moreover, the tissue was found to be devoid of acid alpha-glucosidase mRNA. Gross abnormalities of the acid alpha-glucosidase gene itself were not detected by Southern blot analysis. These results suggest Brahman glycogenosis type II to be caused by a point mutation or a micro deletion/insertion in the acid alpha-glucosidase gene.

Animals↗

Physically mapped, cosmid-derived microsatellite markers as anchor loci on bovine chromosomes.

To identify physical and genetic anchor loci on bovine chromosomes, 13 cosmids, obtained after the screening of partial bovine cosmid libraries with the (CA)n microsatellite motif, were mapped by fluorescence in situ hybridization (FISH). Eleven cosmid probes yielded a specific signal on one of the bovine chromosomes and identified the following loci: D5S2, D5S3, D6S3, D8S1, D11S5, D13S1, D16S5, D17S2, D19S2, D19S3, D21S8. Two cosmids produced centromeric signals on many chromosomes. The microsatellite-containing regions were subcloned and sequenced. The sequence information revealed that the two centromeric cosmids were derived from bovine satellites 1.723 and 1.709, respectively. A cosmid located in the subtelomeric region of Chromosome (Chr) 17 (D17S2) had features of a chromosome-specific satellite. Primers were designed for eight of the nonsatellite cosmids, and seven of these microsatellites were polymorphic with between three and eight alleles on a set of outbred reference families. The polymorphic and chromosomally mapped loci can now be used to physically anchor other bovine polymorphic markers by linkage analysis. The microsatellite primers were also applied to DNA samples of a previously characterized panel of somatic hybrid cell lines, allowing the assignment of seven microsatellite loci to defined syntenic groups. These assignments confirmed earlier mapping results, revealed a probable case of false synteny, and placed two formerly unassigned syntenic groups on specific chromosomes.

Animals↗

The gamma fibrinogen gene (FGG) maps to chromosome 17 in both cattle and sheep.

The gamma fibrinogen gene (FGG) was localised in both cattle and sheep using in situ hybridisation. The probe employed was a 1-kb bovine cDNA fragment. Based on observations of QFQ-banded chromosome preparations, this locus is on bovine chromosome 17q12-->q13 and on the homologous sheep chromosome 17. This localisation is, to our knowledge, the first assignment to chromosome 17 in either the bovine or ovine genome. In addition to localising FGG to this chromosome, the assignment provisionally maps the previously unassigned syntenic group U23, containing (besides FGG) the genes for mitochondrial aldehyde dehydrogenase 2 (ALDH2), interleukin 2 (IL2), immunoglobulin lambda (IGL), and beta fibrinogen (FGB), to chromosome 17 in cattle and probably to the same chromosome in sheep.

Animals↗