Complete mitochondrial DNA (mtDNA) control regions (CR) were sequenced and analysed in order to investigate wild sheep taxonomy and the origin of domestic sheep (Ovis aries). The dataset for phylogenetic analyses includes 63 unique CR sequences from wild sheep of the mouflon (O. musimon, O. orientalis), urial (O. vignei), argali (O. ammon) and bighorn (O. canadensis) groups, and from domestic sheep of Asia, Europe and New Zealand. Domestic sheep occurred in two clearly separated branches with mouflon (O. musimon) mixed into one of the domestic sheep clusters. Genetic distances and molecular datings based on O. canadensis CR and mtDNA protein-coding sequences provide strong evidence for domestications from two mouflon subspecies. Other wild sheep sequences are in two additional well-separated branches. Ovis ammon collium and O. ammon nigrimontana are joined with a specimen from the transkaspian Ust-Urt plateau currently named O. vignei arkal. Ovis ammon ammon, O. ammon darwini and O. vignei bochariensis represent a separate clade and the earliest divergence from the mouflon group. Therefore, O. musimon, O. vignei bochariensis and Ust-Urt sheep are not members of a 'moufloniform' or O. orientalis species, but belong to different clades. Furthermore, Ust-Urt sheep could be a hybrid population or an O. ammon subspecies closely related to O. ammon nigrimontana.
The complete mitochondrial DNA (mtDNA) molecule of the domestic sheep, Ovis aries, was sequenced, together with part of the mtDNA of a specimen representing the other major O. aries haplotype group. The length of the complete ovine mtDNA presented is 16,616 nucleotides (nt). This length is not absolute, however, due to heteroplasmy caused by the occurrence of different numbers of a 75-nt-long tandem repeat in the control region. The sequence data were included in analyses of intraspecific ovine molecular differences, molecular comparisons with bovine mtDNAs, and phylogenetic analyses based on complete mtDNAs. The comparisons with bovine mtDNAs were based on the central domains of the ovine control regions, representing both major ovine haplotype groups, and the corresponding domains of Bos taurus and B. indicus. The comparisons showed that the difference between the bovids was 1.4 times greater than the intraspecific ovine difference. These findings suggest that the strains of wild sheep from which domestic sheep originated were more closely related than were the B. primigenius subspecies which gave rise to B. indicus and B. taurus cattle. Datings based on complete mtDNAs suggest that the bovine and ovine lineages diverged about 30 million years before present. This dating is considerably earlier than that proposed previously.
S-protein, the main inhibitor of the assembly of the membrane attack complex of complement, was isolated from human plasma by a simple purification procedure, which includes barium citrate adsorption, ammonium sulphate precipitation, chromatography on DEAE-Sephacel and Blue Sepharose and gel filtration on Sephacryl S-200. The homogeneous protein (sedimentation coefficient 4.6 S) was obtained in approx. 5% yield relative to its concentration in plasma, which was found to be 0.3-0.5 mg/ml. The final product did not cross-react with antisera against complement proteins or other proteinase inhibitors of human plasma. On polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, S-protein migrated as a single-chain band with an apparent Mr of 74000 under non-reducing conditions and as a doublet of Mr 78000 and 65000 upon reduction. In plasma or serum S-protein also existed in two forms of corresponding Mr values, as was evidenced by an immunoblot enzyme-linked immunosorbent assay technique. S-protein was found to be an acidic glycoprotein with 10% (W/W) carbohydrate content and several isoelectric points in the range pH 4.75-5.25, and it contained one free thiol group per molecule of protein. The functional properties of S-protein in the complement system were demonstrated by its ability to inhibit complement-dependent cell lysis in a concentration-dependent manner (Ki 0.6 microM) and by its incorporation into the nascent SC5b-7 complex. A new function for S-protein could be revealed in the blood coagulation system. The slow progressive inhibition of thrombin by antithrombin III was not affected by S-protein, whereas the purified protein interfered with the fast inactivation of thrombin clotting as well as amidolytic activity by antithrombin III-heparin complex. The acceleration of this inhibition reaction by heparin was counteracted by S-protein, indicating the ability of S-protein to neutralize heparin activity.
A total of 419 individuals of four breeds with differing fecundity (Rhoenschaf, Merinolandschaf, East Friesian Milksheep, Romanov) and several wild sheep of the Ovis musimon, 0. orientalis, 0. vignei and 0. ammon groups were screened for genetic variation at the PA-inhibin (INHBA) locus with up to 11 enzymes. The four breeds differed significantly (P < 0.001) in TaqZ allele frequencies. The frequency of the TaqZ A allele coincided with the average litter size in each breed.
MONTFORT et al. 1992). Nucleotide sequence polymorphism at the a-PAor bB-inhibin loci could lead to differences in the expression of these genes, or structurally different gene products, with subsequent influences on ovulation rate in sheep breeds with differing fecundity. The latter notion is supported by results presented by FLEMING et al. (1992) who detected significantly higher P,-inhibin mRNA levels in follicles of FecB gene carriers compared to controls. Although the INHBA locus was excluded as the site of the FecB mutation (MONTGOMERY et al. 1993), different inhibin alleles could nevertheless contribute to differences in ovulation rate in other sheep breeds. The objective of this study was the identification and characterization of a-, PAand &inhibin alleles as QTL candidates for litter size in sheep. Materials and methods An i m a 1 sA total of 898 sheep of 5 breeds (Merinolandschaf, East Friesian Milksheep, Rhoenschaf, Romanov, Heidschnucke) with different reproductive performance were used in this study. Animals of the Merinolandschaf-and Rhoenschaf breed were maintained at the research station 'Oberer Hardthof', samples from other breeds were obtained on private farms. Two to 10 lambing records per sampled ewe were used to calculate the mean litter size of each breed. Several wild sheep (0. musimon, 0. ammon, 0. vignei) were included as controls. In addition, 123 individuals of the 'AgResearch International Mapping Flock' were used for linkage mapping of the inhibin genes. U.S.
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