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At least 271 records · Page 15Linked to original sources
PubMed1991

Mixed model segregation analysis of LDL-C concentration with genotype-covariate interaction.

Mixed model complex segregation analyses have in the past ignored the possibility of genotype-covariate interaction. Only in the nonmixed model with polygenic heritability equal to zero have segregation analyses been performed that allowed for genotype specific regression of the phenotype on covariates. We present an extension of Hasstedt's [1982] mixed model likelihood approximation which does allow for genotype-covariate interaction in the mixed model. Following description of this approximation, we validate the likelihood calculation by a Monte Carlo procedure based on the actual pedigree and missing data structure used in a complex segregation analysis of low density plus very low density lipoprotein cholesterol (LDL-C + VLDL-C) in baboons. The observed averages of the bootstrap parameter estimates adequately recover the generating values, which included parameters specifying genotype-covariate interaction. We then applied both a traditional complex segregation analysis and an analysis with genotype-covariate interaction to test for the presence of a major locus affecting LDL-C levels in baboons. The model including genotype-covariate interaction was significantly different from the model without interactions, and strongly supported the hypothesis that there is a segregating Mendelian locus as opposed to a random environmental factor. This major locus accounts for approximately 46% of the variance in LDL-C levels, as compared to 40% explained by a locus with no genotype-covariate interaction.

Animals↗
PubMed2006

Segregation of micron-scale membrane sub-domains in live murine sperm.

Lipid rafts, membrane sub-domains enriched in sterols and sphingolipids, are controversial because demonstrations of rafts have often utilized fixed cells. We showed in living sperm that the ganglioside G(M1) localized to a micron-scale membrane sub-domain in the plasma membrane overlying the acrosome. We investigated four models proposed for membrane sub-domain maintenance. G(M1) segregation was maintained in live sperm incubated under non-capacitating conditions, and after sterol efflux, a membrane alteration necessary for capacitation. The complete lack of G(M1) diffusion to the post-acrosomal plasma membrane (PAPM) in live cells argued against the transient confinement zone model. However, within seconds after cessation of sperm motility, G(M1) dramatically redistributed several microns from the acrosomal sub-domain to the post-acrosomal, non-raft sub-domain. This redistribution was not accompanied by movement of sterols, and was induced by the pentameric cholera toxin subunit B (CTB). These data argued against a lipid-lipid interaction model for sub-domain maintenance. Although impossible to rule out a lipid shell model definitively, mice lacking caveolin-1 maintained segregation of both sterols and G(M1), arguing against a role for lipid shells surrounding caveolin-1 in sub-domain maintenance. Scanning electron microscopy of sperm freeze-dried without fixation identified cytoskeletal structures at the sub-domain boundary. Although drugs used to disrupt actin and intermediate filaments had no effect on the segregation of G(M1), we found that disulfide-bonded proteins played a significant role in sub-domain segregation. Together, these data provide an example of membrane sub-domains extreme in terms of size and stability of lipid segregation, and implicate a protein-based membrane compartmentation mechanism.

Adenosine Triphosphate↗
PubMed1994

Host-inhibitory functions encoded by promiscuous plasmids. Transient arrest of Escherichia coli segregants that fail to inherit plasmid RK2.

An effective strategy for a plasmid to be maintained in a growing population of bacteria is to prevent the proliferation of newly formed daughter cells that lack the plasmid. In this study, we determined that the promiscuous, incompatibility group P plasmid RK2 encodes such a system. To induce large numbers of RK2-free segregants of an RK2-containing host, we designed a genetic system that made RK2 replication temperature-sensitive. A double amber mutant of the trfA replication initiator gene was constructed to complement a trfA deletion mutant of an otherwise wild-type RK2 in an Escherichia coli supD(Ts) strain. At the permissive temperature (30 degrees C), RK2 was maintained stably in the strain. Shifting the cells to the non-permissive temperature (42 degrees C) resulted in the nearly synchronous appearance of cells lacking RK2. We found that the number of viable cells rose only slowly over a period of six hours, during which time the cells formed long filaments reaching 20 to 40 times the length of a normal E. coli cell. After six hours, the arrested cells regained the ability to divide and multiply exponentially, and the filaments were eventually reduced to normal-sized cells. Neither arrest nor filamentation required the host recA function. Inhibiting the replication of an RK2 mutant deleted for the par stability locus also induced the arrest of segregants lacking the plasmid, but the arrested cells were not filamented. Our results demonstrate that RK2 encodes at least two functions that are activated in a plasmidless segregant: (1) a filamentation-inducing function specified by the par stability locus, and (2) a post-segregational arrest function (psa) that inhibits the proliferation of plasmidless segregants independent of par. We discuss the possible roles of these functions in the stable maintenance of RK2.

Base Sequence↗
PubMed1998

Trade-off between segregational stability and metabolic burden: a mathematical model of plasmid ColE1 replication control.

A model of ColE1 copy number control has been developed where molecular details of replication are connected both to segregational stability and metabolic burden. Efficient replication control reduces copy number variation and increases segregational stability for a given average copy number. Copy number variation is predicted to depend on the type of inhibition mechanism as well as RNA I and RNA II turnover rate constants. It is shown that when both RNA I and RNA II transcription frequencies and the rate constant for degradation of free RNA I are very large, a hyperbolic inhibition mechanism must compensate with a 1.4 times greater average copy number to obtain the same segregational stability as an exponential inhibition mechanism. How sensitively the replication frequency responds to changes in RNA I concentration depends on the type of inhibition mechanism and the number of attempts to form an RNA II replication primer per plasmid and cell cycle. If RNA I is too stable, it will not follow changes in plasmid concentration closely, and when the transcription frequency for RNA I is only slightly higher than for RNA II, RNA I concentration becomes randomized. In both these cases, the proportionality between the single cell RNA I and plasmid concentrations is lost and this impairs copy number control. Thresholds in the rate for degradation of free RNA I as well as in RNA I and RNA II transcription frequencies have been computed, where an increase in these rate constants has a negligible effect on segregational stability but a corresponding decrease leads to segregational disaster. This indicates that there exists a well defined optimal set of rate constants where the regulation system works well without excessive metabolic load. A number of new experiments are suggested to address features of particular importance for the evolution of ColE1 copy number control.

DNA Replication↗
PubMed1996

Prismatic Metropolis: Race and Residential Segregation in the City of the Angels

Most major urban areas remain segregated by race, especially in terms of black segregation from whites. We replicate and extend the innovative approach developed by Farley and colleagues for understanding processes of racial residential segregation with data collected in Los Angeles. Using a large (N = 4025) multiracial sample of adults, we examine (1) actual and perceived differences in economic status, (2) mutual preference for same race neighbors, and (3) racial prejudice and discrimination as hypotheses for the persistence of residential segregation. With a systematic experimental design we gauge respondent openness to living in areas with varying proportions of black, white, Latino, or Asian neighbors. We find no support for actual or perceived cost of housing as a barrier to integration. Although all groups exhibit some degree of ethnocentric preference for same race neighbors, this tendency is strongest among whites rather than blacks and plays only a small role in perpetuating segregation. Blacks face the greatest hostility in the search for housing and are consensually recognized as most likely to face discrimination in the housing market. Racial minorities are more open to sharing residential space with whites than with other minorities. We find generally higher rates of openness to integration than Farley and colleagues found in their recent Detroit survey.

Journal Article↗
PubMed1995

Statistical properties of segregating sites.

A mutation leading to a segregating site of a sample can be classified by the number of sequences in the sample that inherits the mutant nucleotide; it can also be classified by the frequencies of the two segregating nucleotides at the resulting segregating side. We define the size of a mutation to be the number of sequences in the sample that inherits the mutant nucleotide and the type of mutation (segregating site) to be the smallest value of the frequencies of segregating nucleotides. Each of these two classifications of mutations is analogous to allelic types in a sample of genes. Assuming the neutral Wright-Fisher model, we derived in this paper the mean and variance of the frequency of mutations of each size and type, and the covariance between the numbers of mutations of two different sizes and two different types. Potential applications of these results are discussed.

Analysis of Variance↗
PubMed1998

Probability of a segregating pattern in a sample of DNA sequences.

Mutations that result in segregating sites (polymorphic sites) in a sample of DNA sequences can be classified into different types. A pattern of segregating sites is an array of the numbers of various types of mutations. Using an urn model, the probability of a pattern of segregating sites can be expressed as a recurrence equation and its value can be computed sequentially. Among those that can be computed by this method are the probability of obtaining k external mutations (mutations that occur in external branches of the genealogy of a sample), the probability of obtaining k internal mutations (mutations that occur in internal branches), the probability of obtaining k singletons (segregating sites at which one of the two segregating nucleotides is present in only one sequence), and the probability of obtaining k non-singletons. Two applications of the method are discussed. One is a maximum likelihood estimation of straight theta and another is a Bayesian statistical test of the hypothesis of neutral mutations.

Bayes Theorem↗
PubMed1992

Segregation of transgenes in maize.

Progeny recovered from backcrossed transgenic maize tissue culture regenerants (R0) were analyzed to determine the segregation, expression, and stability of the introduced genes. Transgenic A188 x B73 R0 plants (regenerated from embryogenic suspension culture cells transformed by microprojectile bombardment; see [9]) were pollinated with nontransformed B73 pollen. Inheritance of a selectable marker gene, bar, and a nonselectable marker gene, uidA, was analyzed in progeny (R1) representing four independent transformation events. Activity of the bar gene product, phosphinothricin acetyltransferase (PAT), was assessed in plants comprising the four R1 populations. The number of R1 plants containing PAT activity per total number of R1 plants recovered for each population was 2/7, 19/34, 3/14 and 73/73. Molecular analysis confirmed the segregation of bar in three R1 populations and the lack of segregation in one R1 population. Cosegregation analysis indicated genetic linkage of bar and uidA in all four R1 populations. Analysis of numerous R2 plants derived from crossing transformed R1 plants with nontransformed inbreds revealed 1:1 segregation of PAT activity in three of four lines, including the line that failed to segregate in the R1 generation. Integrated copies of bar in one line appeared to be unstable or poorly transmitted.

Acetyltransferases↗
PubMedDate not supplied

The murine Rb(6.16) translocation: alterations in the proportion of alternate sperm segregants effecting fertilization in vitro and in vivo.

The segregation products of the mouse Rb-(6.16)24 Lub male translocation carrier were analyzed at first cleavage metaphase to determine whether the proportion of normal, balanced, and unbalanced sperm segregants differ in fertilizations occurring in vivo and in vitro. From 34 males, the sperm genomes in 268 first-cleavage mouse embryos were analyzed cytogenetically: 137 and 131 following in vivo and in vitro fertilization, respectively. Both systems demonstrated a preponderance of alternate (67.2% and 54.2%) as compared to adjacent segregation (10.2% and 13.7% as estimated). A contingency table showed that the distribution of reciprocal alternate segregants differed significantly between the two fertilization environments (chi 2 = 20.64, P < 0.0005). Whereas chromosomally normal sperm were 3.6 times more likely than the balanced reciprocals to fertilize in vivo (78.3% normal: 21.7% balanced), 1:1 ratios were recovered following in vitro fertilization (43.7% normal: 56.3% balanced). The data also showed an excess of Y-bearing sperm with the translocation in both in vivo and in vitro fertilization groups. In the latter these segregants were 3 times more likely than X-bearing ones to effect fertilization. These data suggest a phenotypic disadvantage of translocation-X-bearing sperm, possibly mediated through altered haploid gene expression on chromosome 6 and gene expression on the Y. The results show clear evidence for prezygotic selection in vivo and indicate that the environment in which fertilization occurs significantly affects the transmission frequency of this specific translocation.

Animals↗
PubMed1977

Random segregation of sister chromatids in developing chick retinal cells demonstrated in vivo using the fluorescence plus Giemsa technique.

Experiments were designed to test whether nonrandom segregation of sister chromatids at mitosis has a role in the production of cell diversity during embryogenesis, Segregation was examined in vivo in retinal cells from embryonic chicks. Chromatids were labelled with bromouracil and stained by the fluorescence plus Giemsa technique. No evidence of nonrandom segregation was observed in a frequency distribution of pairs of bifilarly labelled sister chromatids at the third metaphase after the start of labeling. Nor was there evidence that chromatids from homologous chromosomes segregated nonrandomly. Nonrandom segregation is probab;y not a mechanism for cell diversification.

Animals↗
PubMed1989

Meiotic segregation of circular plasmid-minichromosomes from intact chromosomes in Saccharomyces cerevisiae.

Distributive disjunction is defined by first meiotic division segregation of either two nonhomologous chromosomes that lack homologous pairing partners, or of two homologous chromosomes that have failed to undergo crossing-over. In the yeast Saccharomyces cerevisiae, plasmid minichromosomes, synthetic linear chromosomes and a fragment of a real chromosome have been observed to segregate from nonhomologous DNA species at the first meiotic divisions. Suggesting that this organism may have a distributive mechanism for chromosome segregation. However, it is not known whether intact chromosomes also participate in a distributive process. To determine whether intact, full length, S. cerevisiae chromosomes could segregate from nonhomologous chromosomal species, the meiotic behavior of an unpaired intact copy of chromosome I has been analyzed with respect to several centromere-containing circular plasmid minichromosomes. Strains monosomic or trisomic for chromosome I were transformed with centromere plasmids containing either homologous or nonhomologous inserts, sporulated, and analyzed genetically both for the presence of plasmid and for the number of copies of chromosome I. Each plasmid segregated from an intact unpaired copy of chromosome I at the first meiotic division in a significant majority (63-93%) of the asci examined. These results suggest that intact chromosomes from S. cerevisiae are capable of distributive disjunction.

Centromere↗
PubMed1989

A direct selection procedure for isolating yeast mutants with an impaired segregation of artificial minichromosomes.

The nondisjunction of artificial yeast minichromosomes (2:0 segregation events) during mitosis is accompanied by the appearance of cells containing more than one copy of the minichromosome. A mathematical simulation of this process has demonstrated that under certain conditions, a nondisjunction of the minichromosomes may result in their accumulation in a considerable portion of the cell population. An increase in the copy number of artificial minichromosomes as a result of impaired segregation has been used to develop a new experimental procedure for directly selecting yeast mutants showing an impaired segregation of artificial minichromosomes during mitosis. Four new genes, AMC1, AMC2, AMC3, and AMC4, which control the segregation of artificial minichromosomes in mitosis, have been identified (AMC3 and AMC4 are mapped to chromosome IV and VII, respectively). Mutations in the genes AMC1-AMC4 also affect the mitotic transmission of natural chromosomes. We suggest that the genes AMC1, AMC2, AMC3, and AMC4 control the segregation of natural chromosomes in yeast.

Chromosomes↗
PubMed1995

Competitive segregation of Si and P on Fe(96.5)Si(3.5) (100) and (110).

Annealing an Fe(96.5)Si(3.5) (100)/(110) bicrystal, containing 90 ppm P, leads immediately to a strong segregation of silicon. The Si atoms, however, desegregate subsequently and are displaced by P, whose segregation enthalpy is larger than that of silicon. The corresponding surface structures formed on both faces have been studied using complementary methods: Scanning tunneling microscopy (STM) to obtain atomically resolved geometrical information and Auger electron spectroscopy (AES) for the determination of the surface composition. Si substitutes surface Fe atoms on both faces and forms ordered surface alloys, whereas P occupies hollow sites on the surface. Si and P form c(2 x 2) superstructures on the (100) surface, whereby each segregated phosphorus atom blocks in the average one silicon segregation site. The (110) surface, on the other hand, is characterized by a c(1 x 3) Si superstructure. Due to the anisotropy of this surface the P/Si exchange proceeds by the formation of silicon coverage decreasing domain boundaries within the silicon structure, which are simultaneously occupied by P atoms. Furthermore the comparison of the AES and STM derived phosphorus coverages indicates a P multilayer segregation on the (110) surface.

Journal Article↗
PubMed2002

Perceptual segregation of overlapping shapes activates posterior extrastriate visual cortex in man.

Objects in natural scenes are rarely seen in isolation, but are usually overlapping or partially occluding other objects. To recognize individual objects, the visual system must be able to segregate overlapping objects from one another. Evidence from lesions in humans and monkeys suggest that perceptual segregation of occluded or overlapping objects involves extrastriate visual cortex. In monkeys, area V4 has been shown to play an important role in recognizing occluded or poorly salient shapes. In humans, a retinotopic homologue of ventral V4 (V4v) has been described, but it is not known whether this area is also functionally homologous to area V4 in monkeys. In this study, we tried to localize the visual cortical regions involved in perceptual segregation of overlapping shapes using positron emission tomography (PET). Regional cerebral blood flow (rCBF) was measured in seven subjects while they discriminated the relative areas of simultaneously presented rectangular shapes. In the control condition, the shapes were displayed without overlaps; in a second condition, the shapes overlapped each other partially. In a third condition, the shapes did not overlap but had been reduced in salience by adding random noise to the stimuli. Contrasting the overlapping shape condition with the control condition identified a single region in the left posterior lateral occipital cortex. The rCBF in this region also increased, though more weakly, during discrimination of shapes embedded in noise, relative to the control condition. The region activated by segregation of overlapping shapes was located in the posterior occipital cortex close to the anterior border of area V2, near the average location of human V4v as determined by retinotopic mapping studies. The activation of this region of extrastriate visual cortex by a task that involved segregation of overlapping shapes is consistent with monkey V4 and human V4v being functionally homologous. We conclude that discrimination of overlapping shapes involves in particular a region of extrastriate visual cortex located in the left lateral occipital cortex and that this region may correspond to human V4v.

Adult↗
PubMed1998

The P22 Erf protein and host RecA provide alternative functions for transductional segregation of plasmid-borne duplications.

A tandem DNA duplication carried on a ColE1-derived plasmid segregates at high frequency upon generalized transduction by phage P22 HT. Transductional segregation of the plasmid-borne duplication can be promoted either by RecA or by the Erf function of P22, indicating that transductional segregation is a consequence of the recombination events that re-circularize the plasmid in the recipient cell. RecA-mediated and Erf-mediated transduction give similar frequencies of duplication segregation and yield the same types of segregation products, indicating that two distinct recombination machineries (RecA + RecBCD and Erf + RecBCD) perform similar or identical recombination reactions on plasmid DNA substrates transduced by bacteriophage P22 HT.

Bacteriophage P22↗
PubMed2004

Co-segregation and heteroplasmy of two coding-region mtDNA mutations within a matrilineal pedigree.

The ENG1 Leber's hereditary optic neuropathy (LHON) family spans six generations and comprises more than 90 maternally related individuals. In this pedigree, the G:A LHON mutation at nucleotide position 11778 shows a complex pattern of segregation in which it is homoplasmic mutant in two branches, homoplasmic wildtype in another, and heteroplasmic in a fourth branch. In addition, there is co-segregation of the 11778 mutant allele and of a G:A silent polymorphism at nucleotide position 5471 in 18 of 19 family members. This co-segregation indicates that the two substitutions arose either simultaneously, or nearly so, in the same "founder" mtDNA molecule. However, the highly divergent mitochondrial allele ratios in the one family member suggest that there has been a complex origin and segregation "history" of these two substitutions. Taking all of the results into consideration, the evidence supports sequential single mutations at sites 5471 and 11778, in close temporal proximity, with subsequent segregation of the intermediate mutational genotype to high levels in one branch of the ENG1 LHON family. In other branches, either the double wildtype or double mutant genotype has become essentially homoplasmic.

DNA, Mitochondrial↗
PubMed2000

Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization.

Meiotic segregation of chromosomes 14 and 21 in sperm from a 14;21 Robertsonian translocation carrier was analyzed with dual-color FISH using two locus-specific DNA probes (Tel 14q and LSI 21). The frequency of normal or chromosomally balanced sperm, resulting from alternate segregation, was 88.42%. The frequency of unbalanced sperm, resulting from adjacent segregation, was 11.25%. These observed frequencies deviated significantly from the theoretical frequencies (33.33% and 66.67%, respectively) based on random chromosome segregation, with sperm resulting from alternate segregation being preferentially produced in the translocation carrier. With respect to the chromosomally unbalanced sperm, the frequency of 21q disomic sperm was 2.45%, which is in agreement with the frequencies of unbalanced fetuses or offspring at the time of amniocentesis or at term (0-4.3%) reported by others. Although the frequency of 14 or 21 nullisomic sperm should be theoretically equal to that of 14q or 21q disomic sperm in both the carrier and controls, the frequency of nullisomic sperm was significantly higher than that of disomic sperm in the carrier (P=0.0009 for chromosome 14, P<0.0001 for chromosome 21) but not in the controls (P=0.091 for chromosome 14, P=0.74 for chromosome 21). This evidence suggests the occurrence of maturation arrest during spermatogenesis of the carrier.

Adult↗
PubMed1989

Effects of cytoskeletal inhibitors on ooplasmic segregation and microtubule organization during fertilization and early development in the ascidian Molgula occidentalis.

The effects of microtubule and microfilament inhibitors on ooplasmic segregation and microtubule organization were examined during fertilization, parthenogenetic activation, and early development in the ascidian Molgula occidentalis. At fertilization the egg cortex contracts as the first phase movement and shortly after mitochondria migrate as the myoplasmic crescent develops in the second phase. The microtubule inhibitors colcemid and nocodazole inhibit the second phase, but not the first phase, of ooplasmic segregation. The microfilament inhibitor cytochalasin E has the reciprocal effect of inhibiting the first, but not the second, phase. It appears that sperm may initially bind at any site on the egg surface and that the contractile activities at the first phase and during polar body formation occur independent of the microtubule system. Since the second phase migration occurs as the sperm astral microtubules assemble and since microtubule, but not microfilament, inhibitors arrest this aspect of ooplasmic segregation, microtubules appear necessary for mitochondrial migration. These results demonstrate that the two phases of ascidian ooplasmic segregation are mediated by different systems, the first by microfilaments and the second by microtubules. The microtubule and microfilament systems appear to operate independent of one another and their combined actions result in the completion of ooplasmic segregation. A model is proposed in which the cortical contraction following fertilization is important not only as the motive force for the first phase movement but also as a method to unite the myoplasm with the entering sperm which can initially bind anywhere on the egg surface. The association between myoplasmic components and the growing sperm aster would ensure that the migration and the spatial distribution of myoplasm in the second phase results in the formation of the myoplasmic crescent.

Animals↗