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At least 19 recordsLinked to original sources
PubMed1992

The use of quantitative genetics for estimating the non-inherited and inherited contributions to metastasis formation.

The contribution of both non-inherited (stochastic, random, environmental, and other non-inherited influences) and inherited factors (genetic and inherited epigenetic factors) to the variability of spontaneous lung metastasis formation in over 100 metastatic lines from each of three murine tumors was measured. The contribution of inherited and genetic sources of variability to metastasis formation was significantly greater than 0 in all cases, but only in the lines of sarcoma SANH was it the major influence on metastatic variability. In the sarcoma SA4020 and hepatocarcinoma HCA-1 lines, non-inherited factors accounted for the majority of the variation in spontaneous lung metastasis formation. A similar situation was also observed in the variability of the tumors with respect to the diameter doubling time. In conclusion, both non-inherited and genetic/inherited factors significantly influenced the formation of spontaneous metastases in the tumors examined. The significance of this finding for the cloning of metastatic genes is discussed.

Animals↗
PubMed1990

Linkage analysis assuming a single-locus mode of inheritance for traits determined by two loci: inferring mode of inheritance and estimating penetrance.

What happens to the results of linkage analysis when one assumes that a disease results from a single genetic locus with reduced penetrance when the actual cause is two epistatically interacting loci? We wanted to (1) determine whether assuming the correct mode of inheritance at the linked locus leads to a higher lod score than assuming the incorrect mode of inheritance irrespective of penetrance assumptions and (2) determine whether it is possible to estimate the apparent penetrance due to the second, unlinked locus from the linkage data. Linkage data were simulated under three different two-locus models. Different "penetrances" were simulated by using different disease allele frequencies at the unlinked locus. Data were then analyzed assuming a single locus with reduced penetrance. The maximum lod score was maximized with respect to penetrance (LVP curves). We found that if there were enough data, assuming the correct (i.e., generating) mode of inheritance at the linked locus always led to a higher lod score than assuming the incorrect mode of inheritance no matter what the penetrance assumption. In contrast to the case where reduced penetrance is due to random factors, the estimate of the apparent penetrance (the "penetrance" due to the second locus) was biased, thus making any estimation of the gene frequency at the second locus doubtful. The ability to detect linkage was apparently not affected when the effects of the second locus were treated as random reduced penetrance. The results suggest that analyzing the data under the assumption of a single-locus model with reduced penetrance rather than a two-locus model will not substantially decrease the ability to establish linkage nor will it affect determining the mode of inheritance at the linked locus from the linkage data.

Computer Simulation↗
PubMed1975

Cytoplasmic inheritance in Saccharomyces cerevisiae: comparison of first zygotic budsite to mitochondrial inheritance patterns.

Zygotic first budsite in Saccharomyces cerevisiae was studied in relation to defined mitochondrial inheritance systems: both petite and drug resistance. It was hypothesized that a highly asymmetric inheritance pattern would be correlated to a high frequency of first budsites on the petite or drug resistant end of the zygote (i.e., that portion of the zygote which was originally the drug resistant or petite haploid before zygote formation). The data collected did not support the hypothesis. For drug resistance, the budsite pattern is identical for a highly biased and a moderately biased inheritance pattern. In a grande by grande cross there is a high probability of the first bud appearing on the conjugation bridge, with lower but equal probabilities of the first bud appearing on one end or the other of the zygote. A grande by petite cross changes this pattern to a high probability of the first bud appearing on the grade end of the zygote, with a lesser probability of the first bud appearing on the conjugation bridge and virtually no budding of the petite end. This phenomenon is independent of degree of neutrality or suppressiveness of the petite strain used, however. The difference between a grande and a grande by petite pattern may be due to the relative functional ability of the mitochondria in each end of the zygote. Tests using antimitochondrial drugs suggest that selection of first budsite on a zygote is a complex phenomenon, not simply dependent upon mitochondrial phenotype. In conclusion, selection of the first zygotic budsite appears to be independent of mitochondrial inheritance patterns.

Cell Division↗
PubMed1976

[Variability and inheritance of behavior in fine-wool sheep. II. Character of inheritance of domesticated behavior and correlation of behavior with productivity traits in fine-wool sheep].

The results of an experimental study of the inheritance of individual behaviour in various types of crosses are presented; the phenotypic and genetic correlations between the behavior and producutivity characters in sheep and the possibility of applying behaviour characteristics to the selection process of fine-wool sheep are analysed. It is shown that the progeny from crosses between parents with the same type of behaviour inherits mainly the type of behaviour of their parents and that, in general, the inheritance has a polygenic character. A genetic relation between the type of domestic behaviour and the productive characters of fine-wool sheep is established. The genetic correlation coefficient between the behaviour and the wool productivity is 0,57, and that between the behaviour and the live weight is 0,53. It is concluded that the inheritance component contributes to the formation of the type of domestic behaviour of fine-wool sheep. Phenotypic and genetic correlations between the type of behaviour and the main productivity characters are discussed. The posibility of using behaviour characteristics as a character under selection is considered.

Animals↗
PubMed1976

Cytoplasmic inheritance in Saccharomyces cerevisiae: comparison of zygotic mitochondrial inheritance patterns.

Mitochondrial movements in Saccharomyces cerevisiae (Sc) zygotes were monitored with phase-contrast microscopy and compared to known mitochondrial inheritance systems. The mitochondria of Sc were convincingly identified by integrated use of phase-contrast, cytochemical and electron microscopic observations. Mitochondria in Sc appear to move by saltatory jumps, which appear to be oriented towards movement of mitochondria into developing buds. Tracking of mitochondria of different genotypes was made possible by positive identification of each mitochondrial population before zygosis, and by the low degree of mixing (less than 10%) of mitochondrial populations before first bud septation. A grande by grande cross demonstrated equal numbers of mitochondria from each haploid moving into the first zygotic bud. A grande by neutral petite cross gave a 2:1 ratio of grande to petite mitochondria. However, a grande by suppressive petite cross gave equal numbers of grande and petite mitochondria. Using drug resistance systems, a comparison was made of highly biased (97%) and moderately biased (71%) chloramphenicol resistant inheritance patterns. In both cases, the ratios of drug resistant to sensitive mitochondria were 1:1. When numbers of mitochondria moving into an individual bud were compared to the phenotypic content of the clone of that bud, no model could be constructed which could predict the latter from the former. The data indicate (with the exception of the neutral petite by grande cross) that the numbers of each mitochondrial type "inserted" into the first zygotic bud are equal, regardless of the degree of asymmetry of inheritance of mitochondrial markers.

Chloramphenicol↗
PubMed1992

The inheritance of vertebral shape in the mouse. I. A study using Fourier analysis to examine patterns of inheritance in the morphology of cervical and upper thoracic vertebrae.

The shapes of cervical and upper thoracic vertebrae from large samples of 2 inbred strains of mice and their F1 offspring were examined using Fourier analysis to investigate in detail the distributions and magnitudes of differences in vertebral shape between different strains of mice, the relationships between parents and offspring and any differences in the inheritance of vertebral shape between successive vertebral levels. Consistent with the findings of an earlier study there was evidence for considerable differences between vertebral levels in the degree to which offspring resemble one or other parent. The results demonstrate that the inheritance of vertebral morphology conforms to a model in which F1s between inbred strains form a triangular relationship with their parents. Furthermore, this relationship varies between vertebral levels. The significance of these findings is considered in relation to the understanding of the mechanisms of character inheritance and evolution and some new directions for research into vertebral column morphogenesis are proposed.

Animals↗
PubMed1977

The lens epithelium of American cocker spaniels with inherited and non-inherited lens cataracts.

The normal lens epithelium of American cocker spaniels exhibits a monolayer of cells similar to that seen in other animals. The lens epithelium from spaniels with presumed inherited cataracts shows a lack of cell division and a decrease in cell density. Lens epithelial preparations from spaniels with presumed non-inherited cataracts show a multilayering of cells with several mitotic figures.

Animals↗
PubMed1976

Extrachromosomal inheritance in Schizosaccharomyces pombe. I. Evidence for an extrakaryotically inherited mutation conferring resistance to antimycin.

In crosses of [ANTr8] with auxotrophic strains, resistance to antimycin segregates almost 50:50 in random spore analysis with a slight preponderance for the sensitivity allele. Tetrad analysis, however, shows all possible types of tetrads (2:2; 3:1; 1:3; 4:0; 0:4 resistant versus sensitive) with an excess of 2:2 segregations and sectoring of colonies on antimycin medium indicating an extrachromosomal mode of inheritance. The overall ratio of resistant versus sensitive spores is the same as compared with random spore data. Using a mutant blocked in meiosis (mei 1) mitotic segregation of stable diploids is achieved, leading to a ratio of 20% resistant to 80% sensitive clones. Possible reasons for the bias in transmission of the resistance determinant is discussed.

Antimycin A↗
PubMed1979

Multifactorial inheritance with cultural transmission and assortative mating. II. a general model of combined polygenic and cultural inheritance.

A general linear model of combined polygenic-cultural inheritance is described. The model allows for phenotypic assortative mating, common environment, maternal and paternal effects, and genic-cultural correlation. General formulae for phenotypic correlation between family members in extended pedigrees are given for both primary and secondary assortative mating. A FORTRAN program BETA, available upon request, is used to provide maximum likelihood estimates of the parameters from reported correlations. American data about IQ and Burks' culture index are analyzed. Both cultural and genetic components of phenotypic variance are observed to make significant and substantial contributions to familial resemblance in IQ. The correlation between the environments of DZ twins is found to equal that of singleton sibs, not that of MZ twins. Burks' culture index is found to be an imperfect measure of midparent IQ rather than an index of home environment as previously assumed. Conditions under which the parameters of the model may be uniquely and precisely estimated are discussed. Interpretation of variance components in the presence of assortative mating and genic-cultural covariance is reviewed. A conservative, but robust, approach to the use of environmental indices is described.

Computers↗
PubMed1976

Extrachromosomal inheritance in Schizosaccharomyces pombe. II. Evidence for extrakaryotically inherited respiratory deficient mutants.

In contrast to the wild-type, mutant [ANTr8] is able spontaneously to throw off stable respiratory deficient mutants. The frequency of these mutants is considerably enhanced by treatment with ethidium bromide (EB) or the azo-dye Janus green (JG). An unstable cell state with a petite-like phenotype is found in both mutant [ANTr8] and wild-type after EB-treatment. However, only in the mutant is this unstable cell state followed by the appearance of stable respiratory deficient (RD) mutants. Formation of microcolonies is observed both in [ANTr8] and wild-type. RD mutants were isolated after EB treatment. Three of them (mit-12, mit-25, and mit-30) were analyzed and mit-25 characterized in more detail.

Ascomycota↗
PubMed1978

Extrachromosomal inheritance in Schizosaccharomyces pombe. VII. Studies by zygote clone analysis on transmission, segregation, recombination, and uniparental inheritance of mitochondrial markers conferring resistance to antimycin, chloramphenicol, and erythromycin.

Crosses involving mitochondrial markers conferring resistance to antimycin (anar, AR), chloramphenicol (capr, CR), and erythromycin (eryr, ER) in cis- and trans-configuration were studied by zygote clone analysis. Mutant anar-8, from which all other drug--resistant isolates were derived, exhibits a highly biased transmission (6.8% anar) in an analysis of 100 individual zygote clones. Important results of zygote clone analyses were:--Zygote clones may contain one, two, three, or four mitochondrial genotypes.--The proportion of the two parental and the two recombinant genotypes in individual zygote clones can vary almost over the entire range of percentages.--Proportions of the two corresponding recombinant types in individual clones are usually unequal.--Transmission rates of markers are higher in trans- than in cis-crosses, indicating additivity of bias by two mutated alleles in coupling.--Transmission rates are different for the three markers both in cis- and trans-crosses, being lowest for CR and highest for ER.--Up to more than 80% uniform clones, expressing only one genotype, can be produced in cis- and trans-crosses. In cis-crosses always the double-sensitive parental type becomes uniform, in trans-crosses this may be the case for parental and/or recombinant genotypes. A tentative map is presented using data from cis- and trans-crosses, including a correction by omission of uniform clones. Phenomena of transmission, segregation, and formation of uniform clones are discussed with special regard to the difference brought about by fission versus budding. A comparison with relevant data from Saccharomyces cerevisiae and other organisms is presented.

Anti-Bacterial Agents↗
PubMed1973

The inheritance of gossypol level in Gossypium. II. Inheritance of seed gosypol in two trains of cultivated Gossypoium barbadense L.

Two strains of cultivated Gossypium barbadense L., Sea Island AS-2 and Pima S-4, were used to study the effects of alleles at two loci on the production and/or storage of gossypol in mature embryos. The normal alleles, Gl(2) and Gl(3), are "native" to G. barbadense, whereas the mutant alleles, gl(2) and gl(3), were introduced from Gossypium hirsutum L. through backcrossing. Each strain was grown in three replications per trial, and one, Sea Island AS-2, was grown in three environments. Each experiment consisted of all possible crosses, including reciprocals, of the four true-breeding genotypes, plus parents. Additive effects accounted for more than 90% of the total genetic variance for seed gossypol level in all trials. Epistatic effects, though small, were frequently significant. In G. barbadense Gl(2) and Gl(3) were associated with the production of similar amounts of gossypol, whereas previous trials with cultivated varieties of G. hirsutum showed that Gl(2) was more than twice as expressive as Gl(3). The greater average productivity of seed gossypol in cultivated G. barbadense, as compared with G. hirsutum, was attributed to greater activity at the Gl(3) locus in the former species.

Chromosome Mapping↗
PubMed1989

Inferring mode of inheritance by comparison of lod scores.

One usually must assume a mode of inheritance when using lod scores for linkage analysis. In this study, we asked the question, "If one assumed mode of inheritance in a linkage analysis gives a higher lod score than another, does that indicate that the mode of inheritance that led to the higher lod score is more 'correct' than the other?" We simulated data under a variety of penetrances, assuming either dominant or recessive inheritance. We then analyzed those simulated data under the correct mode of inheritance, assuming a range of penetrance values, and under the incorrect model, also assuming a range of penetrance values. We found that, if there was enough information for a maximum lod score of at least 3.0, assuming the correct penetrance value or mode of inheritance in the analysis led to a higher lod score than assuming the incorrect penetrance or the incorrect mode of inheritance. These results cannot yet be generalized outside of the specific modes of inheritance and penetrance combinations that we have modeled. Also, penetrance was modeled as "random." The effect of "reduced penetrance" caused by other genetic factors has not yet been tested. We also tested the effect of non-standard ascertainment on drawing conclusions about mode of inheritance from linkage data. Even when families were ascertained only if the family was multiplex (i.e., more than one affected sib), assuming the correct mode of inheritance gave a higher lod score than assuming the incorrect mode of inheritance. This method has the promise of both simplifying and expanding the application of linkage analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

Rates of mutant and inherited structural cytogenetic abnormalities detected at amniocentesis: results on about 63,000 fetuses.

We report data on diagnoses made on amniotic fluid specimens from 1977 to 1984 as reported to the New York State Chromosome Registry. The rate of all de novo (presumed mutant) abnormalities was about 2 per 1,000 in about 61,000 fetuses in which results are unlikely to be biased by the reason for amniocentesis (except for maternal age). This includes about 0.5 per 1,000 de novo markers, about 0.5 per 1,000 other de novo unbalanced, and about 1.0 per 1,000 de novo balanced rearrangements. In about 55,000 fetuses in which rates of inherited abnormalities could be evaluated without apparent bias, the rate of all inherited rearrangement was about 2.9 per 1,000. This includes about 0.3 per 1,000 inherited markers, about 0.2 per 1,000 other inherited unbalanced rearrangements, and about 2.4 per 1,000 inherited balanced abnormalities. Only mutant markers showed a clear association with maternal age (37.6 +/- 2.7 in 24 cases v. 35.8 +/- 3.6 in controls). Inherited markers did not exhibit this trend (35.8 +/- 2.0 in 12 cases v. 36.4 +/- 2.8 in controls). Paternal age does not appear to account for the association. Among abnormalities of known origin, the ratio of mutant to inherited cases is for markers 64:36, for other unbalanced rearrangements 73:27, and for all balanced abnormalities 29:71. In a subgroup of about 55,000 fetuses, of 263 total abnormalities there were 8 instances of apparent true somatic mosaics (5 mutant and 3 of unknown origin but almost certainly mutant). There were also 20 instances of markers in which presumptive somatic loss had resulted in mosaicism (10 mutant, 6 of unknown origin and 4 inherited) and 13 other instances of mosaicism associated with apparent somatic loss (9 mutant, 3 of unknown origin, and 1 inherited). The sex ratio (Y to non-Y karyotypes) for all abnormalities detected was 228:210 (1.09), not different from controls. Only deletions (5:14) and 'other' unbalanced rearrangements (5:13) exhibited a suggestive deviation from this trend. The rates of mutant chromosome rearrangements reported from 1977 to 1983 showed no apparent time cluster, with the possible exception of a peak of markers in 1977, a trend that may be due to higher maternal age in this year. Among fetuses studied because of maternal exposure to putative mutagens there was a non-significant excess of mutants (2.9-5.7 per 1,000 v. 1.7-2.2 per 1,000) and a borderline significant excess of inherited rearrangements (8.6-11.5 per 1,000 v. 2.6-3.1 per 1,000).(ABSTRACT TRUNCATED AT 400 WORDS)

Amniocentesis↗
PubMed1992

Effect of heterogeneity and assumed mode of inheritance on lod scores.

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Linkage↗
PubMed2026

Transgenerational continuity: Persistence as a dimension of inheritance and evolution.

Transgenerational continuity (TC) describes the persistence of inherited molecular architectures across generations. Progress in identity-by-descent (IBD) detection, recombination dynamics, and epigenetic research highlights the growing need for a more comprehensive model of inheritance. This theoretical framework synthesizes evidence from genomics, population studies, and epigenetics to outline how inherited molecular architectures, which are transmitted through IBD, together with heritable epigenetic modifications, can preserve ancestral information across generations. IBD captures genomic continuity across three nested scales, where recent familial segments link close relatives, population-level haplotypes are shared across cohorts, and archaic fragments from Neanderthal and Denisovan admixture persist as molecular fossils of ancient lineages. Although recombination and selection reshape these regions, their persistence across time scales highlights the evolutionary durability of genomic continuity. Epigenetic memory reflects regulatory persistence, whereby molecular modifications can preserve functional states across cell divisions and sometimes across generations. Together with familial and population-level IBD persistence and the long-term retention of introgressed haplotypes, these findings demonstrate that inherited molecular architectures can persist across multiple timescales. Evolutionary processes shape this persistence. Purifying selection preferentially removes deleterious inherited variants, whereas positive selection can favor the persistence of functionally relevant genomic architectures. From this perspective, evolutionary dynamics arise not only from the generation of variation, but also from the differential persistence of inherited molecular architectures through selection. Transgenerational continuity therefore provides a conceptual framework in which persistence serves as an explanatory dimension of inheritance and evolution that complements variation and explains the persistence of biological identity across generations and evolutionary time.

Biological identity↗