The Experts below are selected from a list of 11742 Experts worldwide ranked by ideXlab platform
Claire Rougeulle - One of the best experts on this subject based on the ideXlab platform.
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how many non coding rnas does it take to compensate male female Genetic Imbalance
Advances in Experimental Medicine and Biology, 2016Co-Authors: Jean-françois Ouimette, Claire RougeulleAbstract:Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a Genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage Imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome Genetic Imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.
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How Many Non-coding RNAs Does It Take to Compensate Male/Female Genetic Imbalance?
Non-coding RNA and the Reproductive System, 2015Co-Authors: Jean-françois Ouimette, Claire RougeulleAbstract:Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a Genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage Imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome Genetic Imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.
Beate Brandsaberi - One of the best experts on this subject based on the ideXlab platform.
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morphological classification of nuchal skin in human fetuses with trisomy 21 18 and 13 at 12 18 weeks and in a trisomy 16 mouse
Anatomy and Embryology, 1998Co-Authors: C S Von Kaisenberg, V Krenn, M Ludwig, K H Nicolaides, Beate BrandsaberiAbstract:An increase in the nuchal translucency that can be detected at 10–14 weeks of gestation by ultrasound forms the basis for a screening test for chromosomal abnormality. Several mechanisms leading to this increase in skin thickness have been proposed, including changes of the extracellular matrix, cardiac defects and abnormalities of the large vessels. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12–18 weeks. Immunohistochemistry was applied with monoclonal and polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in expression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses and those with trisomy 21. The ultrastructure of tissue samples was studied by transmission electron microscopy (TEM) and additionally by immunogold TEM. Further, we examined the morphology of the skin in an animal model for Down’s syndrome, the murine trisomy 16, by light and TEM. The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on chromosome 21, was expressed in a wider area than COL6A3, which is located on chromosome 2. Collagen type I was less abundant in the skin of trisomy 18 fetuses, while the skin of all three trisomies contained a dense network of collagen type III and V in comparison with normal fetuses. Collagen type IV, of which two genes are located on chromosome 13, was expressed in the basement membranes of the skin in all fetuses and additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with trisomy 18. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cysts were found in the skin of trisomy 18 and 13, but not in trisomy 21 and normal fetuses. Ultrastructural findings showed that an extracellular precipitate containing glycosaminoglycans was regularly present in the skin of trisomy 21 fetuses and murine trisomy 16 embryos. In conclusion, this study suggests that the skin edema in fetal trisomies is characterized by specific alterations of the extracellular matrix that may be attributed to gene dosage effects as a result of a Genetic Imbalance due to the condition of fetal trisomy.
Jean-françois Ouimette - One of the best experts on this subject based on the ideXlab platform.
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how many non coding rnas does it take to compensate male female Genetic Imbalance
Advances in Experimental Medicine and Biology, 2016Co-Authors: Jean-françois Ouimette, Claire RougeulleAbstract:Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a Genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage Imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome Genetic Imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.
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How Many Non-coding RNAs Does It Take to Compensate Male/Female Genetic Imbalance?
Non-coding RNA and the Reproductive System, 2015Co-Authors: Jean-françois Ouimette, Claire RougeulleAbstract:Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a Genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage Imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome Genetic Imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.
Karl Herrup - One of the best experts on this subject based on the ideXlab platform.
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dna replication precedes neuronal cell death in alzheimer s disease
The Journal of Neuroscience, 2001Co-Authors: Yan Yang, David S Geldmacher, Karl HerrupAbstract:Alzheimer9s disease (AD) is a devastating dementia of late life that is correlated with a region-specific neuronal cell loss. Despite progress in uncovering many of the factors that contribute to the etiology of the disease, the cause of the nerve cell death remains unknown. One promising theory is that the neurons degenerate because they reenter a lethal cell cycle. This theory receives support from immunocytochemical evidence for the reexpression of several cell cycle-related proteins. Direct proof for DNA replication, however, has been lacking. We report here the use of fluorescent in situ hybridization to examine the chromosomal complement of interphase neuronal nuclei in the adult human brain. We demonstrate that a significant fraction of the hippocampal pyramidal and basal forebrain neurons in AD have fully or partially replicated four separate Genetic loci on three different chromosomes. Cells in unaffected regions of the AD brain or in the hippocampus of nondemented age-matched controls show no such anomalies. We conclude that the AD neurons complete a nearly full S phase, but because mitosis is not initiated, the cells remain tetraploid. Quantitative analysis indicates that the Genetic Imbalance persists for many months before the cells die, and we propose that this Imbalance is the direct cause of the neuronal loss in Alzheimer9s disease.
G. M. Taylor - One of the best experts on this subject based on the ideXlab platform.
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Analysis of gene-dosage effects on the expression of CD18 by trisomy 21 lymphoblastoid cell-lines using a statistical model to fit flow cytometry profiles
Human Genetics, 1990Co-Authors: W. G. Bardsley, B. P. Mcmurray, A. Robson, S. D'souza, G. M. TaylorAbstract:It is not clear whether Down syndrome, the phenotypic expression of constitutional trisomy for chromosome 21 (T21), is the result of generalised disruption of homeostasis resulting from Genetic Imbalance, or the over-expression of specific genes on chromosome 21. In order to understand the effect of gene dosage more clearly, we have analysed the predicted and actual levels of expression of the leucocyte integrin β subunit CD 18 on the surface of T21 leucocytes. Previous studies showed that CD 18 expression by T21 lymphoid cell lines (LCL) is greater than on normal LCL. We have now developed a computer model that compares the observed and predicted CD 18 flow cytometric profiles for trisomy 21 LCL. Three parameters (α, β and γ) have been defined that measure different aspects of gene dosage. Using the computer model to calculate these parameters, we have carried out a series of paired comparisons between normal and T21 LCL. The results show that, in some T21 LCL, increased CD 18 expression is proportional to the existing gene dosage, in another set the effect is additive, whereas in others there is a combination of proportional and additive effects. The results suggest that gene regulation can exert pleiotropic effects on gene-dosage, and is consistent with a model in which gene dosage itself is the cause of disrupted homeostasis.