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Showing papers by "Stephen J. O'Brien published in 1980"


Journal ArticleDOI
10 Jan 1980-Nature
TL;DR: The population genetic structures of the Swiss mouse colonies were comparable to an island population in which random fixation, and not inbreeding or population bottlenecks, is apparently responsible for slight losses in genetic variance.
Abstract: The extent of allelic variation has been estimated at 46 structural gene loci within three major colonies of Swiss mice and between inbred derivative strains. The colonies have retained nearly the same amount and type of variation found in natural murine or human populations despite laboratory propagation for more than 50 years (175 generations). The population genetic structures of the Swiss mouse colonies were comparable to an island population in which random fixation, and not inbreeding or population bottlenecks, is apparently responsible for slight losses in genetic variance.

154 citations


Journal ArticleDOI
TL;DR: The allozyme genetic signature represents a definitive monitor of cell identity and is presented as a standard of cell and tissue identification for a variety of biological studies.
Abstract: The electrophoretic resolution of a group of geneticallymonomorphic gene-enzyme systems that are developmentally and biologically ubiquitous has been used to provide a species-specific and type-specific biochemical characterization of various cultured cells. The relative mobilities of gene-enzyme systems representing nine distinct gene products from cell cultures of 25 species fromDrosophils to man are presented. These isoenzymes effectively discriminate interspecies cell-to-cell contamination and almost invariably serve to identify the contaminating species. The resolution of eightpolymorphic gene-enzyme systems in human cell cultures provides a virtually unique allozyme genetic signature as a monitor of intraspecies cellular contamination. The genetic signatures of 47 commonly used human cells are presented. Included in the test were seven putative HeLa (human cervical carcinoma) contaminants each of which expressed a signature identical with that of HeLa. The probability that an unrelated human cell line will have a signature identical to a typed cell is computed for each line from the genotypic frequencies at each locus in a population of cultured human cells. The gene frequencies of this cell population are comparable to the same frequencies in natural human populations. The most common human signature has a frequency (and therefore a probability) of 0.02. The majority of the 17,010 possible signatures are far less probable. A calculation of the theoretical incidence of chance matching of signatures within test groups of two or more individuals is presented. The probability of a chance match between any two randomly selected individuals is 0.004 and among five randomly selected individuals is 0.034. The allozyme genetic signature represents a definitive monitor of cell identity and is presented as a standard of cell and tissue identification for a variety of biological studies.

89 citations


Journal ArticleDOI
TL;DR: Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three Ecotropic viruses are similar to each other and distinct from the target in the LC-amphotropic virus.
Abstract: We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two alleles, Akvr-1R (restrictive) and Akvr-1r (susceptible), in a feral population of mice (Mus) musculus domesticus) at a squab farm near Lake Casitas (LC) in southern California. Akvr-1k is a dominant allele that exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-mediated lymphoma in LC (Akvr-1RR) X AKR F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in backcrosses to AKR mice. Akvr-1R likewise is effective in restriction of NB-tropic Moloney murine leukemia virus-induced viremia and NB-tropic Friend virus-induced splenomegaly but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three ecotropic viruses are similar to each other and distinct from the target in the LC-amphotropic virus. The relationship of Akvr-1 to previously reported murine restriction loci Fv-1, Fv-2, and Fv-4 is discussed.

59 citations


Journal ArticleDOI
TL;DR: Characteristic rearranged human chromosome markers have been observed in a variety of HeLa cell sublines and in five suspected HeLa contaminant lines originally thought to be derived from differentiated tissues of different individual patients.
Abstract: Characteristic rearranged human chromosome markers have been observed in a variety of HeLa cell sublines and in five suspected HeLa contaminant lines originally thought to be derived from differentiat

41 citations



Journal ArticleDOI
11 Dec 1980-Nature
TL;DR: A comparative genetic analysis of electrophoretic variation at 57 homologous biochemical loci of cats, mice and men finds that conservation of the tolerance of genetic polymorphism is apparently more a characteristic of a particular locus than of the vertebrate species or of the genome.
Abstract: The study of the extent and basis of gene-enzyme variation has long been a principal concern of population genetics. Numerous surveys have indicated considerable amounts of genetic variation detectable in natural populations, with few exceptions1–14. The variances of average heterozygosities (H) between species and among populations within species are large, prompting Lewontin to emphasize the importance of large gene sample sizes7 and Selander to encourage analysis of variation of homologous gene-enzyme systems when making species comparisons8. We present here a comparative genetic analysis of electrophoretic variation at 57 homologous biochemical loci of cats, mice and men. The distribution of polymorphism among the sampled loci in the three species was nonrandom. A large group of sampled loci (60%) were monomorphic in all three species, whereas a second group (30%) of the loci were polymorphic in two or more species. This conservation of the tolerance of genetic polymorphism is apparently more a characteristic of a particular locus than of the vertebrate species or of the genome. The current hypotheses for classifying polymorphic and monomorphic loci in terms of physiological and physical enzyme characteristics have been re-examined.

30 citations


Journal ArticleDOI
TL;DR: The viremic LC population appears indistinguishable within the limits of experimental resolution from the virus-negative BC population in its population genetic structure.
Abstract: The Lake Casitas (LC) mouse population located in southwestern Ventura County in California is unusual insofar as 85% of these mice are persistently viremic with congenitally transmitted murine leukemia virus (MuLV). The virus has been identified as the etiological agent responsible for lymphoma and neuromotor paralysis in large numbers of the mice. The majority of other wild mouse populations are generally free of infectious MuLV despite the presence of endogenous cellular DNA sequences homologous to infectious virus isolated from wild mice. Electrophoretic variation in 46 gene-enzyme systems was surveyed using mice from Lake Casitas and from a virus-negative population located in Bouquet Canyon (BC) approximately 40 miles from Lake Casitas. The LC and BC populations are genetically very similar to each other and to feral mouse populations previously studied in California and Europe. In the LC populations 24% of the loci are polymorphic compared to 17% in the BC population. The average heterozygosities for the LC and BC populations are 0.094 and 0.073, respectively. The large amount of genic variation in LC fails to support the concept of the derivation of the colony from a small number of founders. Tests for linkage disequilibrium and/or selective association of viremia and polymorphism at 15 loci located on nine mouse chromosomes did not reveal any nonrandom assortments. The viremic LC population, then, appears indistinguishable within the limits of experimental resolution from the virus-negative BC population in its population genetic structure.

22 citations



Book ChapterDOI
01 Jan 1980
TL;DR: Leukemia-prone wild mice from a squab farm near Lake Casitas in southern California are polymorphic for a restriction gene, named Akvr-1, that suppresses AKR ecotropic virus, which apparently exerts a similar MuLV-suppressive effect in vitro upon various cell types.
Abstract: Leukemia-prone wild mice ( Mus musculus domesticus ) from a squab farm near Lake Casitas (LC) in southern California are polymorphic for a restriction gene, named Akvr-1, that suppresses AKR ecotropic virus. The restriction allele (Akvr-1R) is dominant and exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-associated lymphoma in (LCRR X AKR) F1 hybrids. Ecotropic and xenotropic AKR virus production is also suppressed in thymus, spleen and bone marrow of older resistant F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in F2 and backcrosses to AKR mice. Akvr-1R likewise is effective in restriction of NB-tropic Moloney and Friend MuLVs in vivo but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. This gene apparently exerts a similar MuLV-suppressive effect in vitro upon various cell types. Akvr-1 does not map near to certain retroviral gene loci including Fv-1, Fv-2 and Akv-1. It may be related to the Fv-4 locus described in Japanese mice.