Sex differentiation differs down under.
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Biomedical subjects
Publications and source records attributed to D W Cooper.
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This randomized, double-blind study of 40 patients was designed to determine if the predominant analgesic effect of extradural fentanyl is mediated by a direct spinal action or an indirect systemic one. After Caesarean section, postoperative analgesia was provided for 24 h by patient-controlled extradural analgesia (PCEA group) or by patient-controlled i.v. analgesia (PCIVA group). Both groups received a bolus dose of fentanyl 20 micrograms with a 10-min lockout interval. In the PCIVA group, nine patients stopped early (compared with none in the PCEA group) because of inadequate analgesia. Mean visual analogue pain scores (0-100 mm) at 8 and 12 h were lower for PCEA (23 (sd 13) mm at rest, 31 (23) mm on coughing) than for PCIVA (50 (25) mm at rest, 67 (24) mm on coughing) (P < 0.0005). The mean dose of fentanyl self-administered between 4 and 8 h was lower in the PCEA group (38 (sd 30) micrograms h-1) compared with the PCIVA group (59 (27) micrograms h-1) (P < 0.05). Our results support the hypothesis that the predominant analgesic effect of extradural administration of fentanyl is mediated by a direct spinal action rather than an indirect action from systemic absorption.
OBJECTIVE: To investigate a HLA-G deletion polymorphism in pre-eclamptic pedigrees and the general population. DESIGN: A population association study of HLA-G genotypes from pre-eclamptic/eclamptic patients and control groups. SETTING: Analyses undertaken in the School of Biological Sciences, Macquarie University. Patients were from Royal Women's Hospital, Melbourne, and controls were from Westmead Hospital and Macquarie University, Sydney. SUBJECTS: One hundred and ninety-six individuals, consisting of 29 pre-eclamptic/eclamptic (PE/E) patients, 13 individuals born of a PE/E pregnancy, 46 blood relatives of PE/E patients, 21 husbands of PE/E patients, 25 women normotensive in first pregnancy, 15 husbands of women normotensive in first pregnancy and 47 staff and students of Macquarie University. RESULTS: Genotypic and gene frequencies were not significantly different in the seven groups examined. CONCLUSION: There is no detectable relationship between susceptibility to pre-eclampsia or being born of a pre-eclamptic pregnancy and HLA-G genotype.
Previous work has shown that females have lower recombination rates than males in two distinctly related marsupial species, an American didelphid and an Australian dasyurid. We report here that the tammar wallaby (Macropus eugenii), which belongs to a third major group, has higher female recombination rates in two linked pairs. The nature of the sex differences in recombination rates in this species is thus similar to the situation in eutherian mammals.
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The ovine hair keratin-associated protein (KRTAP) genes are grouped into several families. In this study, we analyzed linkage relationships between members of four KRTAP families and growth hormone and beta-hemoglobin. Restriction fragment length polymorphisms and a microsatellite polymorphism were typed in 10 sire groups from a flock of Australian Merino sheep. Two linkages, both previously undetected in sheep or any other mammal, were found. They were between growth hormone (GH) and the high-sulfur keratin gene family KRTAP1 (previously called high-sulfur B2C) at theta = 0.10, Z = 3.01 and between two high-glycine-tyrosine class genes, KRTAP6 (previously high-glycine-tyrosine type II) and KRTAP8 (previously high-glycine-tyrosine type I-F), at theta = 0.15, Z = 5.0. The high level of conservation of the mammalian genome at these recombination values suggests that these linkages might be found in distantly related mammalian species.
Phosphoglycerate kinase (EC 2.7.2.3; PGK) exists in two forms in marsupials. PGK1 is an X-linked house-keeping enzyme, and PGK2 is a mainly testis-specific enzyme under autosomal control. We have used PGK1 probes derived from two closely related species of macropodid marsupials (kangaroos and wallabies) to demonstrate the existence of a large family of pseudogenes in the tammar wallaby (Macropus eugenii). Over 30 fragments are detectable after Taq digestion. We estimate that there are 25-30 copies per genome. Most are autosomally inherited and are apparently not closely linked. Only two restriction fragments that appeared to be sex linked could be detected. Varying degrees of hybridization of fragments to the probes suggest different levels of homology, and hence different ages of origin. The existence of two PGK1 homologous restriction fragments from the X and a large number from the autosomes was also demonstrated by somatic cell hybridization for two other macropodid species, the wallaroo (M. robustus) and the red kangaroo (M. rufus). These results are compared with those from human and mouse, and it is suggested that the propensity of PGK1 to form pseudogenes is an ancient (approximately 130 MYR BP) characteristic of mammals. The high level of polymorphism detected in the tammar makes these PGK1 probes potentially useful for measuring genetic variability in this species and other macropodids.
The major histocompatibility complex (MHC) loci have been shown to be highly polymorphic in most eutherian ('placental') species studied. Several hypotheses have been advanced for the maintenance of this exceptional level of genetic variation, one of which suggests that it is necessary for successful eutherian reproduction. Marsupials (metatherians) and eutherians are the only two groups of viviparous mammals, but their modes of reproduction are quite distinct. Although marsupials have placentae, they are generally shorter lived and less invasive than in eutherians. Other investigations have shown that genetic variation at marsupial MHC class I loci is probably high. Weak or non-existent mixed lymphocyte culture responses previously reported in several marsupial species have suggested a lack of class II variation. Data have therefore been collected on the level of restriction fragment length polymorphism at MHC class II beta-chain encoding loci of a marsupial, Macropus eugenii (the tammar wallaby). This level is shown to be low, between the level of MHC variation found in cheetahs and a population of lions with a restricted genetic base. Attention is drawn to the need to collect more data on the level of class II variability in both eutherians and marsupials, and to the potential of marsupials for understanding the relation, if any, between mode of reproduction and MHC variability.
Candidate genes for quantitative trait loci have been studied in a Medium Peppin Merino flock. Obvious candidates for effects on wool production traits are genes for the major proteins expressed in the wool fibre, the keratin and keratin-associated protein genes. Two keratin-associated protein loci, KRTAP6 and KRTAP8, have previously been shown to be linked. The results of analyses between these two loci and production traits gave significant evidence of linkage with wool fibre diameter in one out of eight half-sib groups tested. High-glycine-tyrosine proteins (KRTAP6, 7 and 8) are known to vary considerably in abundance in wool fibres and it is possible that a gene for major effect on fibre diameter is located within the same chromosomal region as KRTAP6 and KRTAP8.
An X-linked clone encoding exons 4-9 of the hypoxanthine phosphoribosyltransferase (HPRT) gene was isolated from a kangaroo (Macropus robustus: Marsupialia) lambda EMBL4 genomic library. Sequence similarity between the kangaroo and eutherian HPRT coding sequences was high; however, intron sizes varied significantly between the kangaroo and other eutherian species. HpaII and HhaI sites in the body of the gene were generally hypermethylated in vivo on the active, relative to the inactive X, with sites within intron 3 showing essentially complete correspondence of activity with methylation and inactivity with unmethylation. At approximately 5 kb downstream from the gene, a switch to unmethylation of active X-linked sites occurred. This switch occurred within a cluster of HpaII and HhaI sites that may represent a CG island associated with a subsequent gene.
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In mammals, testis determination is under the control of the testis-determining factor borne by the Y chromosome. SRY, a gene cloned from the sex-determining region of the human Y chromosome, has been equated with the testis-determining factor in man and mouse. We have used a human SRY probe to identify and clone related genes from the Y chromosome of two marsupial species. Comparisons of eutherian and metatherian Y-located SRY sequences suggest rapid evolution of these genes, especially outside the region encoding the DNA-binding HMG box. The SRY homologues, together with the mouse Ube1y homologues, are the first genes to be identified on the marsupial Y chromosome.
cDNA clones for the X-linked PGK-1 were obtained from a tammar wallaby liver by PCR and sequenced. The PGK-1 gene published here is the consensus sequence of those clones. The sequence represents an open reading frame of 1251 bp. Sequence comparisons to X-linked and autosomal sequences showed the greatest homology with the X-linked PGK-1 genes in eutherian species. This sequence opens the way for studying the paternal X inactivation phenomenon in marsupials and will assist in defining the time course of mammalian evolution.
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A cohort of 139 hemophiliacs was typed for HLA D region genes by means of restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene probes. Disease progression was studied in the 65 HIV antibody-positive patients, who were infected by contaminated clotting factor before 1985. Strong associations were found between disease progression in HIV-infected patients and allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was reduced in frequency and a 4.6 kb fragment increased in frequency (p less than 0.005) in the faster progressing group, as measured both by development of CDC Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These results correlate with DR types deduced from the RFLP patterns revealed by DR beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease progression (p less than 0.05).
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