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Nature Structural & Molecular Biology Aug 2023In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate...
In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared with two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanisms of X-to-autosome dosage compensation are still under debate. Here we show that X-chromosomal transcripts have fewer mA modifications and are more stable than their autosomal counterparts. Acute depletion of mA selectively stabilizes autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of mA, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.
Topics: Male; Female; Animals; Mice; Methylation; Dosage Compensation, Genetic; X Chromosome; Mammals; RNA Stability
PubMed: 37202476
DOI: 10.1038/s41594-023-00997-7 -
Fa Yi Xue Za Zhi Jun 2023Tri-allelic pattern in autosomal STR is a common abnormal typing phenomenon in forensic DNA analysis, which brings difficulties and uncertainties to the evaluation of... (Review)
Review
Tri-allelic pattern in autosomal STR is a common abnormal typing phenomenon in forensic DNA analysis, which brings difficulties and uncertainties to the evaluation of the evidence weight in actual cases. This paper reviews the types, formation mechanism, occurrence frequency, genetic pattern and quantitative evaluation of evidence of the tri-allelic pattern in autosomal STR in forensic DNA analysis. This paper mainly explains the formation mechanism and genetic patterns based on different types of tri-allelic pattern. This paper also discusses the determination of tri-allelic pattern and the quantitative method of evidence evaluation in paternity testing and individual identification. This paper aims to provide references for scientific and standardized analysis of this abnormal typing phenomenon in forensic DNA analysis.
Topics: Alleles; DNA; Forensic Medicine; Gene Frequency; Microsatellite Repeats; Humans
PubMed: 37517011
DOI: 10.12116/j.issn.1004-5619.2023.530210 -
Genetic Epidemiology Sep 2018In a genome-wide association study (GWAS), association between genotype and phenotype at autosomal loci is generally tested by regression models. However, X-chromosome...
In a genome-wide association study (GWAS), association between genotype and phenotype at autosomal loci is generally tested by regression models. However, X-chromosome data are often excluded from published analyses of autosomes because of the difference between males and females in number of X chromosomes. Failure to analyze X-chromosome data at all is obviously less than ideal, and can lead to missed discoveries. Even when X-chromosome data are included, they are often analyzed with suboptimal statistics. Several mathematically sensible statistics for X-chromosome association have been proposed. The optimality of these statistics, however, is based on very specific simple genetic models. In addition, while previous simulation studies of these statistics have been informative, they have focused on single-marker tests and have not considered the types of error that occur even under the null hypothesis when the entire X chromosome is scanned. In this study, we comprehensively tested several X-chromosome association statistics using simulation studies that include the entire chromosome. We also considered a wide range of trait models for sex differences and phenotypic effects of X inactivation. We found that models that do not incorporate a sex effect can have large type I error in some cases. We also found that many of the best statistics perform well even when there are modest deviations, such as trait variance differences between the sexes or small sex differences in allele frequencies, from assumptions.
Topics: Alleles; Chromosomes, Human, X; Female; Gene Frequency; Genome-Wide Association Study; Genotype; Humans; Male; Models, Genetic; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait, Heritable; Regression Analysis; X Chromosome Inactivation
PubMed: 29900581
DOI: 10.1002/gepi.22132 -
Fa Yi Xue Za Zhi Oct 2021To develop a multiplex PCR amplification system (EX20+30Y for short) of 19 autosomes, 30 Y-STR loci plus the gender indicator, and evaluate its forensic application...
OBJECTIVES
To develop a multiplex PCR amplification system (EX20+30Y for short) of 19 autosomes, 30 Y-STR loci plus the gender indicator, and evaluate its forensic application value.
METHODS
With the six-color fluorescence labeling technology, a multiplex amplification system of 19 autosomal STR loci and 30 Y-STR loci plus the gender indicator was constructed. Blood samples from 210 unrelated individuals, 69 daily case samples and standard samples 9948 and 9947A were collected for loci detection and analysis. The EX20+30Y multiplex amplification system was evaluated by its sensitivity, mixed sample detection ability, species specificity, balance, direct amplification ability, sample applicability and anti-inhibition ability.
RESULTS
Multiplex amplification of blood samples from 210 unrelated individuals by the detection system obtained accurate genotyping results. The detection sensitivity of standard samples was 0.125 ng and the species specificity was high. The 69 samples from daily cases were genotyped correctly. Moreover, standard sample 9948 could be accurately genotyped even if the samples contained a certain concentration of inhibitors.
CONCLUSIONS
The multiplex amplification system established in this study can conduct combined examination of 19 autosomes, 30 Y-STR loci plus the gender indicator with accurate genotyping and high sensitivity. It has a good forensic application prospect.
Topics: Chromosomes, Human, Y; DNA Fingerprinting; Forensic Medicine; Humans; Microsatellite Repeats; Multiplex Polymerase Chain Reaction; Species Specificity
PubMed: 35187915
DOI: 10.12116/j.issn.1004-5619.2020.500509 -
Genes Aug 2021Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information.... (Review)
Review
Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper , it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook dogma of random chromosome segregation. Recent advances provide a better understanding of meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to bias their segregation. Less understood are mechanisms explaining observations that autosomal heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. We speculate that molecular and cytological mechanisms of non-random segregation might be common in these cases and that there might be a continuous transition between random and non-random segregation which may play a role in the evolution of sexually antagonistic genes and sex chromosome evolution.
Topics: Animals; Centromere; Chromosome Segregation; Chromosomes, Insect; Chromosomes, Mammalian; Chromosomes, Plant; Evolution, Molecular; Female; Humans; Male; Meiosis; Plants; Sex Chromosomes
PubMed: 34573322
DOI: 10.3390/genes12091338 -
Frontiers in Aging Neuroscience 2016Latin-American people with dementia will increase to an astounding 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type like Alzheimer, and... (Review)
Review
Latin-American people with dementia will increase to an astounding 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type like Alzheimer, and vascular dementia (VaD) progression after Cerebrovascular disease is also found. These incidences are increased in Colombia by specific populations affected with pure Neurodegenerative and VaDs like Autosomical Dominant familial Alzheimer's disease (AD) and Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). In spite of the enormous human effort with and economical effort and investment costs, neither sporadic nor genetic kinds of dementia progression have been prevented or blocked yet. Currently, there exist several animal models that partially solve the understanding of the neurodegenerative etiopathogenesis and its treatment. However, when the potential therapies are translated to humans, those do not work or present a limited action. Main difficulties are the diverse comorbility associated to the cause and/or several affected brain regions, reducing the efficacy of some therapies which are limited to a tissue-specific action or modulating a kind of neurotransmission. Global investigation suggests that a general prevention could be achieved with the improvement in the quality of lifestyle, including healthy diet, physical and mental activity, and avoiding mechanical or chemical pro-inflammatory events in an early stage in the most of non-communicable diseases. In this review article, we present some molecular targets and preclinical studies in animal models to propose strategies that could be useful in a future translation to prevent or block neurodegeneration: one is gene therapy; silencing pathogenic genes in critical brain areas where excitotoxicity arise and spread. Another is to take advantage of the natural source and its wide biodiversity of natural products that are capable of identifying, by the blocking and prevention of neurodegeneration. On the other side, the casuistic of pure dementias in the Latin-American region gives an exceptional opportunity to understand the pathogenesis in these human populations. Further, this is in support of the basic and clinical researchers working on an interaction for a better understanding and medical care of mixed dementias, which have more complex factors than pure ones. However, to promote the translation of any therapeutical alternative is necessary to clarify the normative and the protocols for developing clinical trials with original candidates or work upon strategies proposed from South-American countries.
PubMed: 28066230
DOI: 10.3389/fnagi.2016.00304 -
Vavilovskii Zhurnal Genetiki I Selektsii Mar 2023Tuvans are one of the most compactly living peoples of Southern Siberia, settled mainly in the territory of Tuva. The gene pool of the Tuvans is quite isolated, due to...
Tuvans are one of the most compactly living peoples of Southern Siberia, settled mainly in the territory of Tuva. The gene pool of the Tuvans is quite isolated, due to endogamy and a very low frequency of interethnic marriages. The structure of the gene pool of the Tuvans and other Siberian populations was studied using a genome-wide panel of autosomal single nucleotide polymorphic markers and Y-chromosome markers. The results of the analysis of the frequencies of autosomal SNPs by various methods, the similarities in the composition of the Y-chromosome haplogroups and YSTR haplotypes show that the gene pool of the Tuvans is very heterogeneous in terms of the composition of genetic components. It includes the ancient autochthonous Yeniseian component, which dominates among the Chulym Turks and Kets, the East Siberian component, which prevails among the Yakuts and Evenks, and the Far Eastern component, the frequency of which is maximum among the Nivkhs and Udeges. Analysis of the composition of IBD-blocks on autosomes shows the maximum genetic relationship of the Tuvans with the Southern Altaians, Khakas and Shors, who were formed during the settlement of the Turkic groups of populations on the territory of the Altai-Sayan region. A very diverse composition of the Tuvan gene pool is shown for various sublines of Y-chromosomal haplogroups, most of which show strong ethnic specificity. Phylogenetic analysis of individual Y-chromosome haplogroups demonstrates the maximum proximity of the gene pool of the Tuvans with the Altaians, Khakas and Shors. Differences in frequencies of Y-chromosome haplogroups between the Todzhans and Tuvans and a change in the frequencies of haplogroups from south to north associated with the East Asian component were found. The majority of the most frequent Y-chromosome haplogroups in the Tuvans demonstrate the founder effect, the formation age of which is fully consistent with the data on their ethnogenesis.
PubMed: 36923480
DOI: 10.18699/VJGB-23-06 -
The Journal of Obstetrics and... Oct 2015Infertility is a serious social problem in advanced nations, with male factor infertility accounting for approximately half of all cases of infertility. Here, we aim to... (Review)
Review
AIM
Infertility is a serious social problem in advanced nations, with male factor infertility accounting for approximately half of all cases of infertility. Here, we aim to discuss our laboratory results in the context of recent literature on critical genes residing on the Y chromosome or autosomes that play important roles in human spermatogenesis.
METHODS
The PubMed database was systematically searched using the following keywords: 'genetics of male factor infertility'; 'male infertility genes', 'genetics of spermatogenesis' to retrieve information for this review.
RESULTS
Striking progress has recently been made in the elucidation of mechanisms of spermatogenesis using knockout mouse models. This information has, in many cases, not been directly translatable to humans. Nevertheless, mutations in several critical genes have been shown to cause male infertility. We discuss here the contribution to male factor infertility of a number of genes identified in the azoospermia factor (AZF) region on the Y chromosome, as well as the autosomally located genes: SYKP3, KLHL10, AURKC and SPATA16.
CONCLUSIONS
Non-obstructive azoospermia is the most severe form of azoospermia. However, the presence of spermatozoa can only be confirmed through procedures, which may prove to be unnecessary. Elucidation of the genes underlying male factor infertility, and thereby a better understanding of the mechanisms that cause it, will result in more tailored, evidence-based decisions in treatment of patients.
Topics: Animals; Azoospermia; Humans; Male; Y Chromosome
PubMed: 26178295
DOI: 10.1111/jog.12765 -
Frontiers in Cell and Developmental... 2019In mammals, sex chromosomes start to program autosomal gene expression and epigenetic patterns very soon after fertilization. Yet whether the resulting sex differences... (Review)
Review
In mammals, sex chromosomes start to program autosomal gene expression and epigenetic patterns very soon after fertilization. Yet whether the resulting sex differences are perpetuated throughout development and how they connect to the sex-specific expression patterns in adult tissues is not known. There is a dearth of information on the timing and continuity of sex biases during development. It is also unclear whether sex-specific selection operates during embryogenesis. On the other hand, there is mounting evidence that all adult tissues exhibit sex-specific expression patterns, some of which are independent of hormonal influence and due to intrinsic regulatory effects of the sex chromosome constitution. There are many diseases with origins during embryogenesis that also exhibit sex biases. Epigenetics has provided us with viable mechanisms to explain how the genome stores the memory of developmental events. We propose that some of these marks can be traced back to the sex chromosomes, which interact with the autosomes and establish sex-specific epigenetic features soon after fertilization. Sex-biased epigenetic marks that linger after reprograming may reveal themselves at the transcriptional level at later developmental stages and possibly, throughout the lifespan. Detailed molecular information on the ontogeny of sex biases would also elucidate the sex-specific selective pressures operating on embryos and how compensatory mechanisms evolved to resolve sexual conflict.
PubMed: 31552249
DOI: 10.3389/fcell.2019.00186 -
Animals : An Open Access Journal From... Oct 2022Five DSD heifers underwent genetic analysis in the present study. We cytogenetically analyzed in vitro cultured leukocytes and searched for , / and / genes in leukocytes...
Five DSD heifers underwent genetic analysis in the present study. We cytogenetically analyzed in vitro cultured leukocytes and searched for , / and / genes in leukocytes and hair follicles, finding that four of the studied heifers were freemartins (XX/XY leukocyte chimerism). The fifth case had an underdeveloped vulva localized ventrally and cranially to the mammary gland, a normal female sex chromosome complement (60,XX) in the leukocytes, and a lack of Y-chromosome-derived genes in the leukocytes and hair follicles. Postmortem anatomical examination of this heifer revealed the presence of normal ovaries with follicles, uterus, and oviducts, but molecular detection of the , , and genes in these organs indicated the presence of a cell line carrying the Y chromosome. Further analysis of twelve microsatellite markers revealed the presence of additional variants at six loci in DNA samples derived from the reproductive organs; XX/XY chimerism was thus suspected in these samples. On the basis of the detection of (Y-linked) versus (X-linked) and (autosomal) versus genes by droplet digital PCR (ddPCR), the Y/X and Y/autosome ratios were evaluated; they indicated the presence of XX and XY cell lines in the reproductive tissues. Our study showed that XX/XY chimerism can be present in the internal reproductive organs of the virilized heifers with a normal female set of sex chromosomes (60,XX) and a lack of Y-chromosome-derived genes in the leukocytes. The etiology of this phenomenon remains unknown.
PubMed: 36359056
DOI: 10.3390/ani12212932