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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1287-1290, 2020 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-33179242

RESUMO

OBJECTIVE: To explore the pathogenesis and genetic characteristics of a fetus with a der(X)t(X;Y)(p22.3;q11.2) karyotype. METHODS: G-banding karyotyping analysis, BoBs (BACs-on-Beads) assay, and single nucleotide polymorphism array (SNP-array) were used to delineate the structural chromosomal aberration of the fetus. The parents of the fetus were also subjected to karyotyping analysis. RESULTS: The fetus and its mother were both found to have a karyotype of 46,X,add(X)(p22), while the father was normal. BoBs assay indicated that there was a lack of Xp22 but a gain of Yq11 signal. SNP-array confirmed that the fetus and its mother both had a 7.13 Mb deletion at Xp22.33p22.31 (608 021-7 736 547) and gain of a 12.52 Mb fragment at Yq11.221q11.23 (16 271 151-28 788 643). CONCLUSION: The fetus was determined to have a karyotype of 46,X,der(X)t(X;Y)(p22.3;q11.2)mat. The combined use of various methods has facilitated delineation of the fetal chromosomal aberration and prediction of the risk prediction for subsequent pregnancy.


Assuntos
Cromossomos Humanos X , Cromossomos Humanos Y , Diagnóstico Pré-Natal , Bandeamento Cromossômico , Deleção Cromossômica , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Feminino , Feto , Humanos , Cariotipagem , Masculino , Gravidez , Translocação Genética
2.
Science ; 369(6509)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32913072

RESUMO

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.


Assuntos
Regulação da Expressão Gênica , Expressão Gênica , Caracteres Sexuais , Cromossomos Humanos X/genética , Doença/genética , Epigênese Genética , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Especificidade de Órgãos , Regiões Promotoras Genéticas , Locos de Características Quantitativas , Fatores Sexuais
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(9): 942-945, 2020 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-32820504

RESUMO

OBJECTIVE: To explore the genetic basis for a patient with premature ovarian insufficiency. METHODS: Chromosomal G-banding and C-banding, single nucleotide polymorphism array (SNP-array), fluorescence in situ hybridization (FISH) and Y chromosome microdeletion assay were used for the analysis. RESULTS: With the combined techniques, the patient was found to carry a Xq;Yq translocation, with a karyotype of 46,X,der(X)t(X;Y)(q25;q12).ish der(X)(Tel XYp+,Tel XYq+,Yq12+). CONCLUSION: Unbalanced Xq;Yq translocation probably underlay the premature ovarian insufficiency in this patient.


Assuntos
Cromossomos Humanos X/genética , Insuficiência Ovariana Primária , Translocação Genética , Bandeamento Cromossômico , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/genética
5.
Proc Natl Acad Sci U S A ; 117(33): 20063-20069, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32747577

RESUMO

In human populations, the relative levels of neutral diversity on the X and autosomes differ markedly from each other and from the naïve theoretical expectation of 3/4. Here we propose an explanation for these differences based on new theory about the effects of sex-specific life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly longer generation times in males than in females, are expected to have had multiple effects on human X-to-autosome (X:A) diversity ratios, as a result of male-biased mutation rates, the equilibrium X:A ratio of effective population sizes, and the differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for male mutation bias results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal that X:A ratios of effective population sizes are considerably greater than previously appreciated. Finally, we find that the joint effects of historical changes in life history and population size can explain the observed X:A diversity ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous, that non-African populations experienced a substantial reduction in polygyny and/or increase in the male-to-female ratio of generation times around the Out-of-Africa bottleneck, and that current diversity levels were affected by fairly recent changes in sex-specific life history.


Assuntos
Cromossomos Humanos X/genética , Genética Humana , Densidade Demográfica , Biodiversidade , Feminino , Humanos , Masculino , Casamento , Modelos Genéticos , Taxa de Mutação
6.
Nature ; 585(7823): 79-84, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32663838

RESUMO

After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome3, we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.


Assuntos
Cromossomos Humanos X/genética , Genoma Humano/genética , Telômero/genética , Centrômero/genética , Ilhas de CpG/genética , Metilação de DNA , DNA Satélite/genética , Feminino , Humanos , Mola Hidatiforme/genética , Masculino , Gravidez , Reprodutibilidade dos Testes , Testículo/metabolismo
8.
Cytogenet Genome Res ; 160(5): 245-254, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32485717

RESUMO

Chromosomal microdeletion syndromes present with a wide spectrum of clinical phenotypes that depend on the size and gene content of the affected region. In a healthy carrier, epigenetic mechanisms may compensate for the same microdeletion, which may segregate through several generations without any clinical symptoms until the epigenetic modifications no longer function. We report 2 novel cases of Xq24 microdeletions inherited from mothers with extremely skewed X-chromosome inactivation (sXCI). The first case is a boy presenting with X-linked mental retardation, Nascimento type, due to a 168-kb Xq24 microdeletion involving 5 genes (CXorf56, UBE2A, NKRF, SEPT6, and MIR766) inherited from a healthy mother and grandmother with sXCI. In the second family, the presence of a 239-kb Xq24 microdeletion involving 3 additional genes (SLC25A43, SLC25A5-AS1, and SLC25A5) was detected in a woman with sXCI and a history of recurrent pregnancy loss with a maternal family history without reproductive wastages or products of conception. These cases provide evidence that women with an Xq24 microdeletion and sXCI may be at risk for having a child with intellectual disability or for experiencing a pregnancy loss due to the ontogenetic pleiotropy of a chromosomal microdeletion and its incomplete penetrance modified by sXCI.


Assuntos
Aborto Habitual/genética , Deleção Cromossômica , Cromossomos Humanos X/genética , Mães , Enzimas de Conjugação de Ubiquitina/deficiência , Enzimas de Conjugação de Ubiquitina/genética , Inativação do Cromossomo X/genética , Adulto , Pré-Escolar , Epigênese Genética , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/genética , Masculino , Fenótipo , Síndrome , Adulto Jovem
9.
Cell Mol Life Sci ; 77(20): 4069-4080, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32356180

RESUMO

MicroRNAs (miRNA) are small-non coding RNAs endowed with great regulatory power, thus playing key roles not only in almost all physiological pathways, but also in the pathogenesis of several diseases. Surprisingly, genomic distribution analysis revealed the highest density of miRNA sequences on the X chromosome; this evolutionary conserved mammalian feature equips females with a larger miRNA machinery than males. However, miRNAs contribution to some X-related conditions, properties or functions is still poorly explored. With the aim to support and focus research in the field, this review analyzes the literature and databases about X-linked miRNAs, trying to understand how miRNAs could contribute to emerging gender-biased functions and pathological mechanisms, such as immunity and cancer. A fine map of miRNA sequences on the X chromosome is reported, and their known functions are discussed; in addition, bioinformatics functional analyses of the whole X-linked miRNA targetome (predicted and validated) were performed. The emerging scenario points to different gaps in the knowledge that should be filled with future experimental investigations, also in terms of possible implications and pathological perspectives for X chromosome aneuploidy syndromes, such as Turner and Klinefelter syndromes.


Assuntos
Cromossomos Humanos X/genética , MicroRNAs/genética , Animais , Biologia Computacional/métodos , Humanos , Síndrome de Klinefelter/genética , Neoplasias/genética , Síndrome de Turner/genética
10.
G Ital Nefrol ; 37(2)2020 Apr 09.
Artigo em Italiano | MEDLINE | ID: mdl-32281760

RESUMO

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder, mostly caused by antidiuretic hormone receptor type 2 (ADHR2) gene mutations, which are inherited as X-linked traits. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene, inherited in autosomal recessive or dominant manner. We report the case of two adult sisters, of 30 and 27 years of age, diagnosed in early infancy with X-linked CNDI. The patients' sex and family history did not fit in well with this diagnosis, so we sequenced the coding regions of the ADHR2 and AQP2 genes. As expected, no mutations were found in the ADHR2 gene, while we found a compound heterozygosis for two different mutations in the AQP2 gene. A missense mutation (c. 439G>A, p.Ala147Thr), an already known cause of CNDI, and a novel missense putative mutation of an adenine to cytosine at position 551 (c.551A>C), resulting in the substitution of asparagine with threonine at amino acid position 184 (p.Asn184Thr). This second mutation changes a fundamental extracellular Asn-Pro-Ala motif (NPA) of the AQP2 protein, inhibiting its function. Its pathogenicity has been confirmed by in silico predictions and is in line with comparable alterations to the intracellular NPA motif of the AQP2 protein.


Assuntos
Cromossomos Humanos X/genética , Diabetes Insípido Nefrogênico/genética , Receptores de Vasopressinas/genética , Adulto , Aquaporina 2 , Análise Mutacional de DNA , Feminino , Humanos , Mutação de Sentido Incorreto , Linhagem
11.
Nat Commun ; 11(1): 1528, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251294

RESUMO

The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is of concern for their clinical application. However, the effect of different culture conditions on the underlying mutation rate is unknown. Here we show that the mutation rate in two human embryonic stem cell lines derived and banked for clinical application is low and not substantially affected by culture with Rho Kinase inhibitor, commonly used in their routine maintenance. However, the mutation rate is reduced by >50% in cells cultured under 5% oxygen, when we also found alterations in imprint methylation and reversible DNA hypomethylation. Mutations are evenly distributed across the chromosomes, except for a slight increase on the X-chromosome, and an elevation in intergenic regions suggesting that chromatin structure may affect mutation rate. Overall the results suggest that pluripotent stem cells are not subject to unusually high rates of genetic or epigenetic alterations.


Assuntos
Técnicas de Cultura de Células/métodos , Cromossomos Humanos X/genética , DNA Intergênico/genética , Taxa de Mutação , Células-Tronco Pluripotentes/fisiologia , Linhagem Celular , Meios de Cultura/farmacologia , Metilação de DNA , Análise Mutacional de DNA , Epigênese Genética , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Oxigênio/química , Oxigênio/farmacologia , Análise de Sequência de RNA , Sequenciamento Completo do Genoma
12.
Neuron ; 106(5): 759-768.e7, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243781

RESUMO

Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing ∼97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Neurônios/metabolismo , Transtorno do Espectro Autista/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Feminino , Predisposição Genética para Doença , Células HEK293 , Humanos , Células-Tronco Pluripotentes Induzidas , Deficiência Intelectual/genética , Masculino , Mutação , Transporte Proteico/genética
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(5): 584-587, 2020 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-32335892

RESUMO

With the application of BACs-on-BeadsTM (BoBs) and array-comparative genome hybridization (aCGH) technologies in prenatal diagnosis, microdeletion/microduplications at Xp22.3 have been frequently detected. However, the relatively high prevalence and lack of knowledge of such disorders have brought difficulties for clinical genetic counseling. Here, recent progress of research on microdeletion/microduplications at Xp22.3, including epidemiology, pathogenesis, clinical manifestation, and prenatal diagnosis, is reviewed.


Assuntos
Cromossomos Humanos X , Diagnóstico Pré-Natal , Cromossomos Humanos X/genética , Hibridização Genômica Comparativa , Feminino , Aconselhamento Genético , Humanos , Cariotipagem , Gravidez , Pesquisa/tendências
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 471-474, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219840

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus with cleft lip and palate. METHODS: Copy number variations (CNVs) in the fetus and his parents were detected with chromosomal microarray analysis (CMA). RESULTS: As revealed by the CMA assay, the fetus has carried a 228 kb deletion in Xp11.22 region and a 721 kb duplication in 9p21.1. Both CNVs were inherited from the parents. The CNV in Xp11.22 was predicted to be pathogenic by involving the PHF8 gene, whilst the CNV in 9p21.1 was predicted to be benign. CONCLUSION: Deletion of the Xp11.22 region probably underlies the cleft lip and palate in this fetus.


Assuntos
Fenda Labial , Fissura Palatina , Análise em Microsséries , Diagnóstico Pré-Natal , Deleção Cromossômica , Cromossomos Humanos X/genética , Fenda Labial/diagnóstico , Fenda Labial/genética , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Variações do Número de Cópias de DNA , Feminino , Feto , Histona Desmetilases , Humanos , Análise em Microsséries/métodos , Gravidez , Fatores de Transcrição
16.
Zhonghua Fu Chan Ke Za Zhi ; 55(2): 100-105, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32146738

RESUMO

Objective: To investigate the impact of maternal X chromosome aneuploidies on cell free DNA (cf-DNA) prenatal screening. Methods: After genetic counseling, invasive prenatal diagnosis was provided for the 124 cases with high risk of sex chromosome aneuploidie (SCA) indicated by cf-DNA prenatal screening. For cases with discordant results of fetal prenatal diagnosis and cf-DNA prenatal screening, maternal leukocyte was collected for copy number variation sequencing (CNV-seq) to detect whether the maternal X chromosome was carrying variations. Results: Totally, 124 cases with high risks of SCA indicated by cf-DNA prenatal screening, 9 cases refused to take invasive prenatal diagnosis, while the remaining 115 cases received. Among the 115 cases, 41 cases received accordant results with cf-DNA prenatal screening while 74 cases discordant. Among the 74 cases with discordant results, 19 cases were indicated with maternal X chromosome variations by maternal leukocyte CNV-seq, which accounting for 25.7% (19/74) of the SCA false positive cases, and 15.3% (19/124) of all SCA cases. Conclusions: Pregnant women with X chromosome variations may affect the results of cf-DNA prenatal screening, resulting in false positive or false negative outcomes, it should be emphasized that the cf-DNA results may be affected by maternal X chromosome variations. In cases with discordant results of prenatal diagnosis and cf-DNA prenatal screening, maternal leukocyte CNV-seq is recommended to find the reasons of false positive or negative results. And cf-DNA prenatal screening is not recommended for pregnant women who are already known with X chromosome variations.


Assuntos
Aneuploidia , Ácidos Nucleicos Livres/sangue , Cromossomos Humanos X/genética , Variações do Número de Cópias de DNA/genética , Testes para Triagem do Soro Materno/métodos , Diagnóstico Pré-Natal/métodos , Transtornos dos Cromossomos Sexuais/genética , Transtornos Cromossômicos , Feminino , Humanos , Gravidez
17.
Ann Hum Biol ; 47(1): 59-64, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32064953

RESUMO

Background: The value of using X-chromosomal short tandem repeats (X-STRs) as genetic markers in human genetics has been widely recognised. However, the 16 X-STRs in the Goldeneye® DNA ID System 17X kit have not been thoroughly applied.Aim: To investigate the genetic polymorphisms of 16 X-STRs in three main ethnic minorities (Tibetan, Mongolian and Kazakh) in China and to reveal the phylogenetic relationships of different populations.Subjects and methods: A total of 245 Tibetan, 168 Mongolian and 105 Kazakh individuals were genotyped using this 17X kit. The allelic frequencies and other parameters were calculated. An additional eight Chinese populations and nine global populations were included in genetic comparisons based on 16 or 8 overlapped X-STRs.Results: A total of 147 alleles were observed from 16 X-STRs with allelic frequencies ranging from 0.0024 to 0.7952 in the three studied groups. Based on 16 X-STRs, Tibetans, Kazakhs and Mongolians showed more similarity to each other and were genetically distinct from the Shanghai Han group; based on 8 X-STRs, only the genetic relationships between different nations could be clarified.Conclusions: Our study presents an extensive report on a novel X-STR assay in three Chinese ethnic groups and a comprehensive genetic comparison between different populations based on these X-STRs.


Assuntos
Cromossomos Humanos X/genética , Grupos Étnicos/genética , Frequência do Gene , Repetições de Microssatélites , Polimorfismo Genético , China/etnologia , Feminino , Humanos , Filogenia
18.
Nat Commun ; 11(1): 939, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094358

RESUMO

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time.


Assuntos
DNA Antigo , DNA Mitocondrial/genética , Genética Populacional/história , Migração Humana , Modelos Genéticos , Arqueologia/métodos , Restos Mortais , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Conjuntos de Dados como Assunto , Feminino , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , Humanos , Itália , Masculino , Análise de Sequência de DNA
19.
Cytogenet Genome Res ; 160(2): 80-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32018271

RESUMO

Unbalanced X;autosome translocations are a rare occurrence with a wide variability in clinical presentation in which the X chromosome unbalance is usually mitigated by a favorable X inactivation pattern. In most cases, this compensation mechanism is incomplete, and the patients show a syndromic clinical presentation. We report the case of a family with 4 women, of 3 different generations, carrying an unbalanced X;7 translocation with a derivative X;7 chromosome and showing a skewed X inactivation pattern with a preferential activation of the normal X. None of the carriers show intellectual disability, and all of them have a very mild clinical presentation mainly characterized by gynecological/hormonal issues and autoimmune disorders. We underline the necessity of family testing for a correct genetic consultation, especially in the field of prenatal diagnosis. We indeed discuss the fact that X;autosome translocations may lead to self-immunization, as skewed X chromosome inactivation has already been proved to be related to autoimmune disorders.


Assuntos
Doenças Autoimunes/genética , Transtornos Cromossômicos/genética , Cromossomos Humanos X/genética , Translocação Genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Linhagem , Fenótipo , Gravidez , Inativação do Cromossomo X
20.
Exp Hematol ; 83: 2-11, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32001340

RESUMO

The history of clonal hematopoiesis (CH) research is punctuated by several seminal discoveries that have forged our understanding of cancer development. The clever application of the principle of random X-chromosome inactivation (XCI) in females led to the development of the first test to identify clonal derivation of cells. Initially limited by a low level of informativeness, the applicability of these assays expanded with differential methylation-based assays at highly polymorphic genes such as the human androgen receptor (HUMARA). Twenty years ago, the observation that skewing of XCI ratios increases as women age was the first clue that led to the identification of mutations in the TET2 gene in hematologically normal aging individuals. In 2014, large-scale genomic approaches of three cohorts allowed definition of CH, which was reported to increase the risk of developing hematologic cancers and cardiovascular diseases. These observations created a fertile field of investigation aimed at investigating the etiology and consequences of CH. The most frequently mutated genes in CH are DNMT3A, TET2, and ASXL1, which have a role in hematopoietic stem cell (HSC) development and self-renewal. These mutations confer a competitive advantage to the CH clones. However, the penetrance of CH is age dependent but incomplete, suggesting the influence of extrinsic factors. Recent data attribute a modest role to genetic predisposition, but several observations point to the impact of a pro-inflammatory milieu that advantages the mutated clones. CH may be a barometer of nonhealthy aging, and interventions devised at curbing its initiation or progression should be a research priority.


Assuntos
Envelhecimento/genética , Pesquisa Biomédica/história , Cromossomos Humanos X/genética , Hematopoese/genética , Mutação , Inativação do Cromossomo X , Adulto , Proteínas de Ligação a DNA/genética , Feminino , Células-Tronco Hematopoéticas , História do Século XX , História do Século XXI , Humanos , Masculino , Proteínas Proto-Oncogênicas/genética , Receptores Androgênicos/genética , Proteínas Repressoras/genética
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