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Carmen Sapienza - One of the best experts on this subject based on the ideXlab platform.
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natural selection and the evolution of Genome Imprinting
Annual Review of Genetics, 2003Co-Authors: Elena De La Casaesperon, Carmen SapienzaAbstract:▪ Abstract Sexual reproduction results from the fusion of gametes in which the chromatin configuration of maternal and paternal chromosomes is distinct at fertilization. Although many of the differences are erased during successive cellular divisions and chromatin modifications, some are retained in both somatic and germline cells. These epigenetic modifications can confer different characteristics on maternal and paternal chromosomes and such differences can be selected during any process that has the ability to distinguish between homologues. The end result of these selective forces are parental origin effects, writ large. The range of effects observed, including transcriptional Imprinting and effects on chromosome segregation and heterochromatization, reflects the diversity of selective forces in operation. However, a closer look at these effects suggests that parental origin–dependent differences in chromatin structure might be subject to some common forces and that these forces may explain many of th...
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natural selection and the function of Genome Imprinting beyond the silenced minority
Trends in Genetics, 2000Co-Authors: Fernando Pardo-manuel De Villena, Elena De La Casaesperon, Carmen SapienzaAbstract:Most hypotheses of the evolutionary origin of Genome Imprinting assume that the biochemical character on which natural selection has operated is the expression of the allele from only one parent at an affected locus. We propose an alternative - that natural selection has operated on differences in the chromatin structure of maternal and paternal chromosomes to facilitate pairing during meiosis and to maintain the distinction between homologues during DNA repair and recombination in both meiotic and mitotic cells. Maintenance of differences in chromatin structure in somatic cells can sometimes result in the transcription of only one allele at a locus. This pattern of transcription might be selected, in some instances, for reasons that are unrelated to the original establishment of the imprint. Differences in the chromatin structure of homologous chromosomes might facilitate pairing and recombination during meiosis, but some such differences could also result in non-random segregation of chromosomes, leading to parental-origin-dependent transmission ratio distortion. This hypothesis unites two broad classes of parental origin effects under a single selective force and identifies a single substrate through which Mendel's first and second laws might be violated.
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A role for modifier genes in Genome Imprinting.
Results and problems in cell differentiation, 1999Co-Authors: C. Cristofre Martin, Carmen SapienzaAbstract:It is, by now, an old observation that the phenotype elicited by a mutant allele at a particular locus is not the sole result of the DNA sequence of that allele. The truth of this statement may be easily recognized by comparing different individuals within the same family, each of whom has the same genetic disease. Siblings who have neurofibromatosis, for example, all share the same disease allele at the NF1 locus but the manifestations of disease (number and size of cafe au lait spots, number and size of neurofibromas, presence of neurofibrosarcoma, etc.) among the siblings may vary dramatically (Easton et al. 1993). These variations in disease phenotype between individuals who carry the same mutant allele have been subsumed under the mechanistically vague concept that many diseases exhibit variable expressivity (Thompson et al. 1991). Such differences in disease phenotype may result from many factors, including stochastic processes and environmental influences, but at least some of these differences are thought to result from the collective action of additional genetic factors that differ between individuals. These additional genetic factors are said to modify the phenotype and are, therefore, called modifier genes.
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the polar lethal ovum mutant gene maps to the distal portion of mouse chromosome 11
Genetics, 1992Co-Authors: Carmen Sapienza, J Paquette, P Pannunzio, S Albrechtson, Kenneth MorganAbstract:Genetics, Vol 132, 241-246, Copyright © 1992 | * * * | || | ### INVESTIGATIONS | C. Sapienza, J. Paquette, P. Pannunzio, S. Albrechtson and K. Morgan Ludwig Institute for Cancer Research and Department of Medicine, University of California, San Diego, La Jolla, California 92093-0660 Genome Imprinting is the process by which identical alleles at a particular locus may be rendered functionally different depending on the sex of the parent contributing the allele. While several mutations in imprinted genes have been defined, no variants in the regulatory system that gives rise to Imprinting have been described. Here we report our genetic analysis of the behavior of the interstrain, polar, embryonic-lethal phenotype known as the ``DDK syndrome.'' We have mapped the interstrain, polar-lethal region of the Genome to the distal portion of mouse chromosome 11, near the Xmv-42 locus. We propose that the lethal phenotype is not caused by a standard mutation, but by aberrant Imprinting of a gene within this region.
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Genome Imprinting and carcinogenesis
Biochimica et Biophysica Acta, 1991Co-Authors: Carmen SapienzaAbstract:Abstract The preferential retention of paternal tumor suppression alleles in sporadic tumors and the failure to demonstrate genetic linkage between disease predisposition and tumor suppressor loci in familial cases indicates that Genome Imprinting may be involved in the genesis of some pediatric cancers. A genetic model that invokes the activity of modifier loci (Imprinting genes) on alleles to be modified (imprinted genes) is able to account for these data. Genome Imprinting may be viewed as a special case of dominance modification, differing from other examples only in that the modification of dominance is dependent on gamete-of-origin. Data from human pediatric tumors, transgenes in the mouse and variegating position-effects in Drosophila, indicate that the net effect of modifier loci is the inactivation of alleles at affected loci. Polymorphism at the level of the modifier loci will result in different degrees of modification between individuals. With respect to tumors, the most important mechanism by which these differences are manifested is cellular mosaicism for the expression of a modified allele. Such characteristics are reminiscent of the behavior of variegating position-effects in Drosophila and the application of this paradign to human disease phenotypes provides both a mechanism by which differential Genome Imprinting may be accomplished as well as genetic models that may explain the clinical association of syntenic diseases, the association between tumor progression and specific chromosomal aneuploidy and the unusual inheritance characteristics of many diseases.
Azim M Surani - One of the best experts on this subject based on the ideXlab platform.
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influence of Genome Imprinting on gene expression phenotypic variations and development
Human Reproduction, 1991Co-Authors: Azim M SuraniAbstract:Genome Imprinting confers functional differences on parental chromosomes as a result of the differences in epigenetic inheritance from parental germlines. Repressed and derepressed chromatin structures probably constitute the initial germline-dependent 'imprints'. Any subsequent modifications, such as DNA methylation, will be influenced by these initial epigenetic modifications. Hence, epigenetic modifications of parental alleles probably occur progressively and this will affect their potential for expression. It appears that Imprinting of some parental alleles is critical for their dosage, affecting embryonic growth, cell proliferation and differentiation. Genetic studies highlight the influence of subsets of imprinted genes and identify those which are crucial for development. Genomic Imprinting also affects some transgene loci and dominant mutations with accompanying variable penetrance and expressivity. The response of transgenes can be influenced by modifier genes whose presence is most readily detected in different inbred backgrounds. The influence of modifier genes can in turn be affected by their parental origin, perhaps partly by the maternally inherited oocyte cytoplasmic factors, as well as by complex interactions between some parental alleles and oocyte cytoplasmic factors. The resulting epigenetic modifications of unlinked loci can result in substantial phenotypic variations.
Fernando Pardo-manuel De Villena - One of the best experts on this subject based on the ideXlab platform.
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Genome Imprinting regulated by the mouse Polycomb group protein Eed.
Nature genetics, 2003Co-Authors: Jesse Mager, Nathan D. Montgomery, Fernando Pardo-manuel De Villena, Terry MagnusonAbstract:Epigenetic regulation is essential for temporal, tissue-specific and parent-of-origin-dependent gene expression. It has recently been found that the mouse Polycomb group (PcG) gene Eed (embryonic ectoderm development) acts to maintain repression of the imprinted X chromosome. Here, we investigated whether Eed is also required for regulation of autosomal imprinted loci. Expression analyses showed that transcripts from the silent alleles of a subset of paternally repressed genes were present in Eed(-/-) embryos. Parent-of-origin methylation was preserved in these embryos, but we observed changes in the methylation status of specific CpGs in differentially methylated regions (DMRs) at affected but not at unaffected loci. These data identify Eed as a member of a new class of trans-acting factors that regulate parent-of-origin expression at imprinted loci.
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natural selection and the function of Genome Imprinting beyond the silenced minority
Trends in Genetics, 2000Co-Authors: Fernando Pardo-manuel De Villena, Elena De La Casaesperon, Carmen SapienzaAbstract:Most hypotheses of the evolutionary origin of Genome Imprinting assume that the biochemical character on which natural selection has operated is the expression of the allele from only one parent at an affected locus. We propose an alternative - that natural selection has operated on differences in the chromatin structure of maternal and paternal chromosomes to facilitate pairing during meiosis and to maintain the distinction between homologues during DNA repair and recombination in both meiotic and mitotic cells. Maintenance of differences in chromatin structure in somatic cells can sometimes result in the transcription of only one allele at a locus. This pattern of transcription might be selected, in some instances, for reasons that are unrelated to the original establishment of the imprint. Differences in the chromatin structure of homologous chromosomes might facilitate pairing and recombination during meiosis, but some such differences could also result in non-random segregation of chromosomes, leading to parental-origin-dependent transmission ratio distortion. This hypothesis unites two broad classes of parental origin effects under a single selective force and identifies a single substrate through which Mendel's first and second laws might be violated.
Kenneth Morgan - One of the best experts on this subject based on the ideXlab platform.
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the polar lethal ovum mutant gene maps to the distal portion of mouse chromosome 11
Genetics, 1992Co-Authors: Carmen Sapienza, J Paquette, P Pannunzio, S Albrechtson, Kenneth MorganAbstract:Genetics, Vol 132, 241-246, Copyright © 1992 | * * * | || | ### INVESTIGATIONS | C. Sapienza, J. Paquette, P. Pannunzio, S. Albrechtson and K. Morgan Ludwig Institute for Cancer Research and Department of Medicine, University of California, San Diego, La Jolla, California 92093-0660 Genome Imprinting is the process by which identical alleles at a particular locus may be rendered functionally different depending on the sex of the parent contributing the allele. While several mutations in imprinted genes have been defined, no variants in the regulatory system that gives rise to Imprinting have been described. Here we report our genetic analysis of the behavior of the interstrain, polar, embryonic-lethal phenotype known as the ``DDK syndrome.'' We have mapped the interstrain, polar-lethal region of the Genome to the distal portion of mouse chromosome 11, near the Xmv-42 locus. We propose that the lethal phenotype is not caused by a standard mutation, but by aberrant Imprinting of a gene within this region.
Barbara Wabik-Śliz - One of the best experts on this subject based on the ideXlab platform.
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Frequency of X-Y chromosome dissociation in mouse spermatocytes from interstrain crosses, recombinant inbred strains, and chimeras: Possible involvement of paternal Genome Imprinting
Molecular reproduction and development, 1994Co-Authors: Halina Krzanowska, Barbara Wabik-ŚlizAbstract:The frequency of dissociation of the X-Y chromosome bivalent in diakinesis-metaphase I spermatocytes differs significantly between two inbred mouse strains, CBA (29%) and KE (7%), that were used to obtain reciprocal F1 hybrids, and to develop recombinant inbred (R1) strains. The level of X-Y dissociation was significantly higher in (KExCBA)F1 hybrids sired by the CBA males (24%) than in reciprocal F1 hybrids (12%), revealing the inheritance after the father. Among 14 RI strains, nine were concordant with KE, one with CBA, and four had intermediate phenotype, significantly different from both progenitor strains. This shows that at least two genes are involved, and their possible linkage with agouti and Trf loci is suggested. The linkage with agouti was confirmed by testing additional 10 CBXE incipient RI strains. There was no significant difference in the level of X-Y dissociation between EXCB RI strains derived from the original cross sired by the CBA males and CBXE RI strains derived from the reciprocal cross. The involvement of the Y chromosome-linked factors was unlikely because it was found earlier (Krzanowska, 1989: Gamete Res 23:357–365) that two congenic strains, KE and KE.CBA, differing with respect to the source of the Y chromosome, had the same level of X-Y dissociation. Thus, the difference obtained between reciprocal F1 hybrids is interpreted in terms of paternal Genome Imprinting imposed by CBA males and propagated only in the presence of some alleles derived from this strain. Analysis of six KE ⟷ CBA-T6 chimeras, among them three germ line chimeras, points to the conclusion that the tendency to low or high level of X-Y chromosome dissociation is expressed rather autonomously by KE or CBA-T6 spermatocytes (as recognized by a marker chromosome pair), respectively, and was not modified by the presence of somatic cells of the opposite strain. © 1994 Wiley-Liss, Inc.