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Trends in Genetics : TIG Nov 2019X inactivation presents two longstanding puzzles: the counting and choice of X chromosomes. Here, we consider counting and choice in the context of pairing, both of the...
X inactivation presents two longstanding puzzles: the counting and choice of X chromosomes. Here, we consider counting and choice in the context of pairing, both of the X and of the autosomes.
Topics: Animals; Chromosome Pairing; Chromosomes; Humans; Mammals; Mice; Models, Genetic; X Chromosome; X Chromosome Inactivation
PubMed: 31521404
DOI: 10.1016/j.tig.2019.07.010 -
Cell Jan 2024X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across the X chromosome...
X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across the X chromosome in cis to mediate gene silencing chromosome-wide. In female naive human pluripotent stem cells (hPSCs), XIST is in a dispersed configuration, and XCI does not occur, raising questions about XIST's function. We found that XIST spreads across the X chromosome and induces dampening of X-linked gene expression in naive hPSCs. Surprisingly, XIST also targets specific autosomal regions, where it induces repressive chromatin changes and gene expression dampening. Thereby, XIST equalizes X-linked gene dosage between male and female cells while inducing differences in autosomes. The dispersed Xist configuration and autosomal localization also occur transiently during XCI initiation in mouse PSCs. Together, our study identifies XIST as the regulator of X chromosome dampening, uncovers an evolutionarily conserved trans-acting role of XIST/Xist, and reveals a correlation between XIST/Xist dispersal and autosomal targeting.
Topics: Animals; Female; Humans; Male; Mice; Gene Silencing; Genes, X-Linked; RNA, Long Noncoding; X Chromosome; Pluripotent Stem Cells
PubMed: 38181737
DOI: 10.1016/j.cell.2023.11.033 -
The American Journal of Dermatopathology Oct 2022PTEN hamartoma tumor syndrome (PTHS) includes diseases with germline pathogenic variants in the PTEN gene. Cowden syndrome is included in this syndrome . PTEN... (Review)
Review
PTEN hamartoma tumor syndrome (PTHS) includes diseases with germline pathogenic variants in the PTEN gene. Cowden syndrome is included in this syndrome . PTEN (phosphatase and tensin homolog) is a tumor suppressor gene located on chromosome 10q22-23; nearly 60%-90% of pathogenic variants are inherited. Cowden syndrome is a rare autosomic dominant condition, affecting approximately 1/200,000 people worldwide. Patients present benign and, malignant neoplasms in multiple organs, mostly breast and thyroid. The skin is the organ affected most consistently by Cowden disease. It is an autosomal dominant condition, characterized clinically by the presence of innumerable verrucous lesions on the skin. Interpretations of histopathologic findings in the cutaneous and mucosal lesions continue to be a matter of debate.
Topics: Hamartoma Syndrome, Multiple; Humans; Skin
PubMed: 36122333
DOI: 10.1097/DAD.0000000000002234 -
International Journal of Molecular... Feb 2023Primary ovarian insufficiency (POI) is a heterogeneous disease resulting from non-functional ovaries in women before the age of 40. It is characterized by primary... (Review)
Review
Primary ovarian insufficiency (POI) is a heterogeneous disease resulting from non-functional ovaries in women before the age of 40. It is characterized by primary amenorrhea or secondary amenorrhea. As regards its etiology, although many POI cases are idiopathic, menopausal age is a heritable trait and genetic factors play an important role in all POI cases with known causes, accounting for approximately 20% to 25% of cases. This paper reviews the selected genetic causes implicated in POI and examines their pathogenic mechanisms to show the crucial role of genetic effects on POI. The genetic factors that can be found in POI cases include chromosomal abnormalities (e.g., X chromosomal aneuploidies, structural X chromosomal abnormalities, X-autosome translocations, and autosomal variations), single gene mutations (e.g., newborn ovary homeobox gene (NOBOX), folliculogenesis specific bHLH transcription factor (FIGLA), follicle-stimulating hormone receptor (FSHR), forkhead box L2 (FOXL2), bone morphogenetic protein 15 (BMP15), etc., as well as defects in mitochondrial functions and non-coding RNAs (small ncRNAs and long ncRNAs). These findings are beneficial for doctors to diagnose idiopathic POI cases and predict the risk of POI in women.
Topics: Female; Humans; Infant, Newborn; Amenorrhea; Chromosome Aberrations; Mutation; Primary Ovarian Insufficiency
PubMed: 36901862
DOI: 10.3390/ijms24054423 -
Journal of Evolutionary Biology Dec 2022Sex chromosomes are common features of animal genomes, often carrying a sex determination gene responsible for initiating the development of sexually dimorphic traits.... (Review)
Review
Sex chromosomes are common features of animal genomes, often carrying a sex determination gene responsible for initiating the development of sexually dimorphic traits. The specific chromosome that serves as the sex chromosome differs across taxa as a result of fusions between sex chromosomes and autosomes, along with sex chromosome turnover-autosomes becoming sex chromosomes and sex chromosomes 'reverting' back to autosomes. In addition, the types of genes on sex chromosomes frequently differ from the autosomes, and genes on sex chromosomes often evolve faster than autosomal genes. Sex-specific selection pressures, such as sexual antagonism and sexual selection, are hypothesized to be responsible for sex chromosome turnovers, the unique gene content of sex chromosomes and the accelerated evolutionary rates of genes on sex chromosomes. Sex-specific selection has pronounced effects on sex chromosomes because their sex-biased inheritance can tilt the balance of selection in favour of one sex. Despite the general consensus that sex-specific selection affects sex chromosome evolution, most population genetic models are agnostic as to the specific sources of these sex-specific selection pressures, and many of the details about the effects of sex-specific selection remain unresolved. Here, I review the evidence that ecological factors, including variable selection across heterogeneous environments and conflicts between sexual and natural selection, can be important determinants of sex-specific selection pressures that shape sex chromosome evolution. I also explain how studying the ecology of sex chromosome evolution can help us understand important and unresolved aspects of both sex chromosome evolution and sex-specific selection.
Topics: Animals; Male; Female; Sex Chromosomes; Selection, Genetic; Sex Determination Processes; Inheritance Patterns; Phenotype; Evolution, Molecular
PubMed: 35950939
DOI: 10.1111/jeb.14074 -
Molecular Ecology Oct 2018In two papers published at about the same time almost thirty years ago, Frank (Evolution, 45, 1991a, 262) and Hurst and Pomiankowski (Genetics, 128, 1991, 841)... (Review)
Review
In two papers published at about the same time almost thirty years ago, Frank (Evolution, 45, 1991a, 262) and Hurst and Pomiankowski (Genetics, 128, 1991, 841) independently suggested that divergence of meiotic drive systems-comprising genes that cheat meiosis and genes that suppress this cheating-might provide a general explanation for Haldane's rule and the large X-effect in interspecific hybrids. Although at the time, the idea was met with skepticism and a conspicuous absence of empirical support, the tide has since turned. Some of the clearest mechanistic explanations we have for hybrid male sterility involve meiotic drive systems, and several other cases of hybrid sterility are suggestive of a role for meiotic drive. In this article, I review these ideas and their descendants and catalog the current evidence for the meiotic drive model of speciation. In addition, I suggest that meiotic drive is not the only intragenomic conflict to involve the X chromosome and contribute to hybrid incompatibility. Sexually and parentally antagonistic selection pressures can also pit the X chromosome and autosomes against each other. The resulting intragenomic conflicts should lead to co-evolution within populations and divergence between them, thus increasing the likelihood of incompatibilities in hybrids. I provide a sketch of these ideas and interpret some empirical patterns in the light of these additional X-autosome conflicts.
Topics: Animals; Female; Genetic Speciation; Hybridization, Genetic; Infertility, Male; Male; Meiosis; Models, Genetic; Repetitive Sequences, Nucleic Acid; X Chromosome
PubMed: 29281152
DOI: 10.1111/mec.14471 -
Diagnostics (Basel, Switzerland) Jul 2023Marfan syndrome (MFS) is a rare inherited autosomic disorder, which encompasses a variety of systemic manifestations caused by mutations in the Fibrillin-1 encoding gene... (Review)
Review
Marfan syndrome (MFS) is a rare inherited autosomic disorder, which encompasses a variety of systemic manifestations caused by mutations in the Fibrillin-1 encoding gene (). Cardinal clinical phenotypes of MFS are highly variable in terms of severity, and commonly involve cardiovascular, ocular, and musculoskeletal systems with a wide range of manifestations, such as ascending aorta aneurysms and dissection, mitral valve prolapse, ectopia lentis and long bone overgrowth, respectively. Of note, an accurate and prompt diagnosis is pivotal in order to provide the best treatment to the patients as early as possible. To date, the diagnosis of the syndrome has relied upon a systemic score calculation as well as DNA mutation identification. The aim of this review is to summarize the latest MFS evidence regarding the definition, differences and similarities with other connective tissue pathologies with severe systemic phenotypes (e.g., Autosomal dominant Weill-Marchesani syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome) and clinical assessment. In this regard, the management of MFS requires a multidisciplinary team in order to accurately control the evolution of the most severe and potentially life-threatening complications. Based on recent findings in the literature and our clinical experience, we propose a multidisciplinary approach involving specialists in different clinical fields (i.e., cardiologists, surgeons, ophthalmologists, orthopedics, pneumologists, neurologists, endocrinologists, geneticists, and psychologists) to comprehensively characterize, treat, and manage MFS patients with a personalized medicine approach.
PubMed: 37443678
DOI: 10.3390/diagnostics13132284 -
Therapeutic Advances in Musculoskeletal... 2019Hypophosphatasia is a rare inherited disease caused by a loss of function mutations in the gene that codes for the tissue-nonspecific alkaline phosphatase enzyme. It is... (Review)
Review
Hypophosphatasia is a rare inherited disease caused by a loss of function mutations in the gene that codes for the tissue-nonspecific alkaline phosphatase enzyme. It is autosomally inherited and at least 388 different genetic defects have been identified. The clinical presentation is variable from a severe perinatal form, that is fatal if untreated, to adult-onset disease. This review covers the pathophysiology, diagnosis and current management option including the recently licensed enzyme replacement therapy asfotase alfa.
PubMed: 31413732
DOI: 10.1177/1759720X19863997 -
Seminars in Cell & Developmental Biology Aug 2016Males are XY and females are XX in most mammalian species. Other species such as birds have a different sex chromosome make-up: ZZ in males and ZW in females. In both... (Review)
Review
Males are XY and females are XX in most mammalian species. Other species such as birds have a different sex chromosome make-up: ZZ in males and ZW in females. In both types of organisms one of the sex chromosomes, Y or W, has degenerated due to lack of recombination with its respective homolog X or Z. Since autosomes are present in two copies in diploid organisms the heterogametic sex has become a natural "aneuploid" with haploinsufficiency for X- or Z-linked genes. Specific mechanisms have evolved to restore a balance between critical gene products throughout the genome and between males and females. Some of these mechanisms were co-opted from and/or added to compensatory processes that alleviate autosomal aneuploidy. Surprisingly, several modes of dosage compensation have evolved. In this review we will consider the evidence for dosage compensation and the molecular mechanisms implicated.
Topics: Alleles; Aneuploidy; Animals; Dosage Compensation, Genetic; Evolution, Molecular; Humans; Sex Chromosomes; Up-Regulation
PubMed: 27112542
DOI: 10.1016/j.semcdb.2016.04.013