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Menopause (New York, N.Y.) Jul 2016The pathophysiology of primary ovarian insufficiency (POI) is not well elucidated. Many candidate genetic aberrations are on the X-chromosome; on the contrary, many... (Review)
Review
OBJECTIVE
The pathophysiology of primary ovarian insufficiency (POI) is not well elucidated. Many candidate genetic aberrations are on the X-chromosome; on the contrary, many genetic perturbations are also on the autosomes. The aim of this review is to summarize the knowledge of genetic aberrations on autosomes from chromosomal rearrangement, gene abnormality, genome-wide association studies and epigenetics.
METHODS
Searches of electronic databases were performed. Articles and abstracts relevant to POI and genetic studies associated with autosomes were summarized in this interpretive literature review.
RESULTS
Various genetic aberrations located on the autosomes were found. These abnormalities are from chromosomal rearrangement, which might disrupt the critical region on chromosome loci or disturbance of the meiosis process. Specific gene aberrations are also identified. The genes that have functions in ovarian development, folliculogenesis, and steroidogenesis on autosomes are proposed to be involved from gene association studies. Gene-to-gene interaction or epistasis also might play a role in POI occurrence. Recently, genetic techniques to study the whole genome have emerged. Although no specific conclusion has been made, the studies using genome-wide association to find the specific aberration throughout the genome in POI have been published. Epigenetic mechanisms might also take part in the pathogenesis of POI.
CONCLUSIONS
The considerably complex process of POI is still not well understood. Further research is needed for gene functional validation studies to confirm the contribution of genes in POI, or additional genome-wide association studies using novel clustered regularly interspaced short palindromic repeat/Cas9 technique might make these mechanisms more comprehensible.
Topics: Chromosome Aberrations; Chromosome Disorders; Epigenesis, Genetic; Female; Genome-Wide Association Study; Humans; Primary Ovarian Insufficiency
PubMed: 27045702
DOI: 10.1097/GME.0000000000000603 -
Molecular Ecology Aug 2023Fast-X evolution has been observed in a range of heteromorphic sex chromosomes. However, it remains unclear how early in the process of sex chromosome differentiation...
Fast-X evolution has been observed in a range of heteromorphic sex chromosomes. However, it remains unclear how early in the process of sex chromosome differentiation the Fast-X effect becomes detectible. Recently, we uncovered an extreme variation in sex chromosome heteromorphism across poeciliid fish species. The common guppy, Poecilia reticulata, Endler's guppy, P. wingei, swamp guppy, P. picta and para guppy, P. parae, appear to share the same XY system and exhibit a remarkable range of heteromorphism. Species outside this group lack this sex chromosome system. We combined analyses of sequence divergence and polymorphism data across poeciliids to investigate X chromosome evolution as a function of hemizygosity and reveal the causes for Fast-X effects. Consistent with the extent of Y degeneration in each species, we detect higher rates of divergence on the X relative to autosomes, a signal of Fast-X evolution, in P. picta and P. parae, species with high levels of X hemizygosity in males. In P. reticulata, which exhibits largely homomorphic sex chromosomes and little evidence of hemizygosity, we observe no change in the rate of evolution of X-linked relative to autosomal genes. In P. wingei, the species with intermediate sex chromosome differentiation, we see an increase in the rate of nonsynonymous substitutions on the older stratum of divergence only. We also use our comparative approach to test for the time of origin of the sex chromosomes in this clade. Taken together, our study reveals an important role of hemizygosity in Fast-X evolution.
Topics: Male; Animals; Sex Chromosomes; X Chromosome; Polymorphism, Genetic; Genes, X-Linked; Poecilia; Evolution, Molecular
PubMed: 37309716
DOI: 10.1111/mec.17048 -
Theoretical Population Biology Oct 2019In contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots...
In contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots for sexual conflict. Similarly, the maternal inheritance of the mitochondrial genome (mtDNA) means that mutations that are beneficial in females can spread in a population even if they are deleterious in males, a form of sexual conflict known as Mother's Curse. While both Mother's Curse and sex chromosome induced sexual conflict have been well studied on their own, the interaction between mitochondrial genes and genes on sex chromosomes is poorly understood. Here, we use analytical models and computer simulations to perform a comprehensive examination of how transmission asymmetries of nuclear, mitochondrial, and sex chromosome-linked genes may both cause and resolve sexual conflicts. For example, the accumulation of male-biased Mother's Curse mtDNA mutations will lead to selection in males for compensatory nuclear modifier loci that alleviate the effect. We show how the Y chromosome, being strictly paternally transmitted provides a particularly safe harbor for such modifiers. This analytical framework also allows us to discover a novel kind of sexual conflict, by which Y chromosome-autosome epistasis may result in the spread of male beneficial but female deleterious mutations in a population. We christen this phenomenon Father's Curse. Extending this analytical framework to ZW sex chromosome systems, where males are the heterogametic sex, we also show how W-autosome epistasis can lead to a novel kind of nuclear Mother's Curse. Overall, this study provides a comprehensive framework to understand how genetic transmission asymmetries may both cause and resolve sexual conflicts.
Topics: Chromosomes, Human, Y; DNA, Mitochondrial; Fathers; Female; Humans; Male; Models, Theoretical; Mothers; Selection, Genetic; Sex Chromosome Aberrations; Sex Chromosomes
PubMed: 31054851
DOI: 10.1016/j.tpb.2018.12.007 -
Genes May 2022Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and...
Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and as such are located in different genomic positions. To investigate retroposition patterns and retrogene expression, we computationally identified interchromosomal retroduplication events in nine portions of the phylogenetic history of malaria mosquitoes, making use of species that do or do not have classical sex chromosomes to test the roles of sex-linkage. We found 40 interchromosomal events and a significant excess of retroduplications from the X chromosome to autosomes among a set of young retrogenes. These young retroposition events occurred within the last 100 million years in lineages where all species possessed differentiated sex chromosomes. An analysis of available microarray and RNA-seq expression data for showed that many of the young retrogenes evolved male-biased expression in the reproductive organs. Young autosomal retrogenes with increased meiotic or postmeiotic expression in the testes tend to be male biased. In contrast, older retrogenes, i.e., in lineages with undifferentiated sex chromosomes, do not show this particular chromosomal bias and are enriched for female-biased expression in reproductive organs. Our reverse-transcription PCR data indicates that most of the youngest retrogenes, which originated within the last 47.6 million years in the subgenus , evolved non-uniform expression patterns across body parts in the males and females of . Finally, gene annotation revealed that mitochondrial function is a prominent feature of the young autosomal retrogenes. We conclude that mRNA-mediated gene duplication has produced a set of genes that contribute to mosquito reproductive functions and that different biases are revealed after the sex chromosomes evolve. Overall, these results suggest potential roles for the evolution of meiotic sex chromosome inactivation in males and of sexually antagonistic conflict related to mitochondrial energy function as the main selective pressures for X-to-autosome gene reduplication and testis-biased expression in these mosquito lineages.
Topics: Animals; Anopheles; Female; Malaria; Male; Phylogeny; Retroelements; Sex Chromosomes
PubMed: 35741730
DOI: 10.3390/genes13060968 -
Chromosome Research : An International... Jun 2023In the evolution of many organisms, periods of slow genome reorganization (= chromosomal conservatism) are interrupted by bursts of numerous chromosomal changes...
In the evolution of many organisms, periods of slow genome reorganization (= chromosomal conservatism) are interrupted by bursts of numerous chromosomal changes (= chromosomal megaevolution). Using comparative analysis of chromosome-level genome assemblies, we investigated these processes in blue butterflies (Lycaenidae). We demonstrate that the phase of chromosome number conservatism is characterized by the stability of most autosomes and dynamic evolution of the sex chromosome Z, resulting in multiple variants of NeoZ chromosomes due to autosome-sex chromosome fusions. In contrast during the phase of rapid chromosomal evolution, the explosive increase in chromosome number occurs mainly through simple chromosomal fissions. We show that chromosomal megaevolution is a highly non-random canalized process, and in two phylogenetically independent Lysandra lineages, the drastic parallel increase in number of fragmented chromosomes was achieved, at least partially, through reuse of the same ancestral chromosomal breakpoints. In species showing chromosome number doubling, we found no blocks of duplicated sequences or duplicated chromosomes, thus refuting the hypothesis of polyploidy. In the studied taxa, long blocks of interstitial telomere sequences (ITSs) consist of (TTAGG) arrays interspersed with telomere-specific retrotransposons. ITSs are sporadically present in rapidly evolving Lysandra karyotypes, but not in the species with ancestral chromosome number. Therefore, we hypothesize that the transposition of telomeric sequences may be triggers of the rapid chromosome number increase. Finally, we discuss the hypothetical genomic and population mechanisms of chromosomal megaevolution and argue that the disproportionally high evolutionary role of the Z sex chromosome can be additionally reinforced by sex chromosome-autosome fusions and Z-chromosome inversions.
Topics: Animals; Butterflies; Telomere; Karyotype; Sex Chromosomes; Genome; Evolution, Molecular
PubMed: 37300756
DOI: 10.1007/s10577-023-09725-9 -
Genes Feb 2024Sex chromosome turnover is the transition between sex chromosomes and autosomes. Although many cases have been reported in poikilothermic vertebrates, their evolutionary...
Sex chromosome turnover is the transition between sex chromosomes and autosomes. Although many cases have been reported in poikilothermic vertebrates, their evolutionary causes and genetic mechanisms remain unclear. In this study, we report multiple transitions between the Y chromosome and autosome in the Japanese Tago's brown frog complex. Using chromosome banding and molecular analyses (sex-linked and autosomal single nucleotide polymorphisms, SNPs, from the nuclear genome), we investigated the frogs of geographic populations ranging from northern to southern Japan of two species, and (2n = 26). Particularly, the Chiba populations of East Japan and Akita populations of North Japan have been, for the first time, investigated here. As a result, we identified three different sex chromosomes, namely chromosomes 3, 7, and 13, in the populations of the two species. Furthermore, we found that the transition between the Y chromosome (chromosome 7) and autosome was repeated through hybridization between two or three different populations belonging to the two species, followed by restricted chromosome introgression. These dynamic sex chromosome turnovers represent the first such findings in vertebrates and imply that speciation associated with inter- or intraspecific hybridization plays an important role in sex chromosome turnover in frogs.
Topics: Animals; Humans; Anura; Sex Chromosomes; Ranidae; Biological Evolution; Chromosomes, Human, Y
PubMed: 38540359
DOI: 10.3390/genes15030300 -
Prenatal Diagnosis Dec 2017To review the literature for survival and phenotypes of liveborns with autosomal monosomy to inform decisions regarding transfer of in vitro fertilization-derived... (Review)
Review
Should embryos with autosomal monosomy by preimplantation genetic testing for aneuploidy be transferred?: Implications for embryo selection from a systematic literature review of autosomal monosomy survivors.
OBJECTIVE
To review the literature for survival and phenotypes of liveborns with autosomal monosomy to inform decisions regarding transfer of in vitro fertilization-derived embryos reported as monosomic on preimplantation genetic testing for aneuploidy (PGT-A).
METHOD
Ovid-Medline and EMBASE were systematically searched to identify published case reports of liveborn individuals with autosomal monosomy, full or mosaic, for a whole chromosome.
RESULTS
Fifty-three reports describing 56 individuals with autosomal monosomy met the selection criteria: 1 case each of monosomy 14 and 16, 3 each for monosomy 15 and 18, 1 for group "E", 5 for monosomy 20, 24 for monosomy 21, 7 for monosomy 22, and eleven for a "G" group chromosome. There were no reports with monosomy for the larger chromosomes 1 through 13, nor for chromosomes 17 or 19, autosomes with highest gene density. Most reported individuals had severe handicaps and died in infancy with some surviving longer.
CONCLUSION
Given potential for survival of handicapped individuals with autosomal monosomy for chromosomes 14, 15, 16, 18, 20, 21, and 22, low priority should be given to transfer of embryos apparently monosomic for these chromosomes. Couples electing transfer of monosomic embryos should consider amniocentesis for ongoing pregnancies but should be informed of its limitations.
Topics: Contraindications, Procedure; Embryo Transfer; Humans; Live Birth; Monosomy; Mosaicism; Preimplantation Diagnosis
PubMed: 29164644
DOI: 10.1002/pd.5185 -
Genome Biology and Evolution Apr 2019Sex chromosomes play a central role in genetics of speciation and their turnover was suggested to promote divergence. In vertebrates, sex chromosome-autosome fusions...
Sex chromosomes play a central role in genetics of speciation and their turnover was suggested to promote divergence. In vertebrates, sex chromosome-autosome fusions resulting in neo-sex chromosomes occur frequently in male heterogametic taxa (XX/XY), but are rare in groups with female heterogamety (WZ/ZZ). We examined sex chromosomes of seven pests of the diverse lepidopteran superfamily Gelechioidea and confirmed the presence of neo-sex chromosomes in their karyotypes. Two synteny blocks, which correspond to autosomes 7 (LG7) and 27 (LG27) in the ancestral lepidopteran karyotype exemplified by the linkage map of Biston betularia (Geometridae), were identified as sex-linked in the tomato leafminer, Tuta absoluta (Gelechiidae). Testing for sex-linkage performed in other species revealed that while LG7 fused to sex chromosomes in a common ancestor of all Gelechioidea, the second fusion between the resulting neo-sex chromosome and the other autosome is confined to the tribe Gnoreschemini (Gelechiinae). Our data accentuate an emerging pattern of high incidence of neo-sex chromosomes in Lepidoptera, the largest clade with WZ/ZZ sex chromosome system, which suggest that the paucity of neo-sex chromosomes is not an intrinsic feature of female heterogamety. Furthermore, LG7 contains one of the major clusters of UDP-glucosyltransferases, which are involved in the detoxification of plant secondary metabolites. Sex chromosome evolution in Gelechioidea thus supports an earlier hypothesis postulating that lepidopteran sex chromosome-autosome fusions can be driven by selection for association of Z-linked preference or host-independent isolation genes with larval performance and thus can contribute to ecological specialization and speciation of moths.
Topics: Animals; Biological Evolution; DNA Barcoding, Taxonomic; Female; Karyotype; Male; Moths; Sex Chromosomes; Synteny
PubMed: 31028711
DOI: 10.1093/gbe/evz075 -
Scientific Reports Nov 2023We generated single haplotype assemblies from a hinny hybrid which significantly improved the gapless contiguity for horse and donkey autosomal genomes and the X...
We generated single haplotype assemblies from a hinny hybrid which significantly improved the gapless contiguity for horse and donkey autosomal genomes and the X chromosomes. We added over 15 Mb of missing sequence to both X chromosomes, 60 Mb to donkey autosomes and corrected numerous errors in donkey and some in horse reference genomes. We resolved functionally important X-linked repeats: the DXZ4 macrosatellite and ampliconic Equine Testis Specific Transcript Y7 (ETSTY7). We pinpointed the location of the pseudoautosomal boundaries (PAB) and determined the size of the horse (1.8 Mb) and donkey (1.88 Mb) pseudoautosomal regions (PARs). We discovered distinct differences in horse and donkey PABs: a testis-expressed gene, XKR3Y, spans horse PAB with exons1-2 located in Y and exon3 in the X-Y PAR, whereas the donkey XKR3Y is Y-specific. DXZ4 had a similar ~ 8 kb monomer in both species with 10 copies in horse and 20 in donkey. We assigned hundreds of copies of ETSTY7, a sequence horizontally transferred from Parascaris and massively amplified in equids, to horse and donkey X chromosomes and three autosomes. The findings and products contribute to molecular studies of equid biology and advance research on X-linked conditions, sex chromosome regulation and evolution in equids.
Topics: Male; Horses; Animals; Equidae; X Chromosome; Sex Chromosomes; Genome
PubMed: 37978222
DOI: 10.1038/s41598-023-47583-x -
Genome Biology Nov 2021Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome...
BACKGROUND
Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear.
RESULTS
Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency.
CONCLUSIONS
Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.
Topics: Alleles; Aneuploidy; Animals; Cellular Reprogramming; Chromatin; Gene Regulatory Networks; Induced Pluripotent Stem Cells; Mice; RNA-Seq; Single-Cell Analysis; Transcription Factors; Transcription, Genetic; X Chromosome; X Chromosome Inactivation
PubMed: 34724962
DOI: 10.1186/s13059-021-02518-5