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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(2): 182-185, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32034751

RESUMO

OBJECTIVE: To perform prenatal diagosis for two fetuses carrying partial deletion of Y chromosome. METHODS: Routine G- and C-banding were carried out to analyze the chromosomal karyotypes of the fetuses and their fathers. Fetal DNA was also subjected to low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), SRY gene and AZF factor testing. RESULTS: Both fetuses showed a 46, XN, del(Y) (q11.2) karyotype at 320-400 band level by the analysis of amniotic fluid chromosomes. FISH with Y chromosome centromere probe indicated that in both cases the number of Y chromosome was normal. Both fathers had an apparently normal karyotype at 320-400 band level. For fetus 1, CNV-seq test revealed a 12.88 Mb deletion at Yq11.221-q12, which encompassed the whole of AZFb+AZFc regions and may lead to male infertility, sperm deficiency and/or severe oligospermia. In fetus 2, CNV-seq also detected a 14.84 Mb deletion at Yq11.21-q12, which encompassed the whole of the AZF region and may lead to severe spermatogenesis disorder resulting in severe oligoasthenospermia and azoospermia. In both cases, testing of SRY gene was positive. No point mutation of the SRY gene was identified. Analysis of amniotic fluid DNA confirmed partial or total absence of AZF in the two fetuses, respectively. CONCLUSION: Combined use of various technologies can enable accurate detection of structural abnormalities of the Y chromosome and facilitate genetic counseling. CNV-seq can help with rapid screening of Y chromosome microdeletions and may be used as a complementary test for chromosomal karyotyping.


Assuntos
Cromossomos Humanos Y , Oligospermia , Deleção Cromossômica , Variações do Número de Cópias de DNA , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Infertilidade Masculina , Masculino , Gravidez , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual
2.
Hum Genet ; 139(4): 421-446, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32020362

RESUMO

Y chromosome (ChrY), the male-specific sex chromosome, has been considered as a genetic wasteland. Aging-related mosaic loss of ChrY (LOY) has been known for more than half a century, but it was constantly considered as a neutral karyotype related to normal aging. These views have been challenged with genome-wide association studies identifying mosaic LOY in human somatic cells is the most commonly acquired mutation in male's genome and is associated with a wide spectrum of human diseases including cancer, Alzheimer's disease, and cardiovascular disease. These previously undescribed clinical significances deeply modify our perception on ChrY and open up a range of new questions. Here, we review the latest advances in our knowledge of the biological origins and clinical consequences of mosaic LOY. We highlight the association of mosaic LOY to pathogenic conditions and evaluate the cause-and-consequence relationships between mosaic LOY and pathogenesis. The known risk factors of mosaic LOY including age, genetic variants, ChrY structural aberrations and environmental stressors are discussed. In light of evidence from pioneering and more recent studies, we propose the micronucleation hypothesis and centromere-dysfunction and telomere-attrition models to explain how mosaic LOY occurs and why ChrY is prone to lose. We believe it is importantly and timely to extend mosaic LOY research from epidemiological associations to mechanistic studies. In this regard, we outline important gaps and assess several future directions from a biological and clinical perspective. An improved understanding of mosaic LOY will open new pathways to modify and increase healthy aging in males.


Assuntos
Doença de Alzheimer , Doenças Cardiovasculares , Cromossomos Humanos Y , Mosaicismo , Neoplasias , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Cromossomos Humanos Y/genética , Cromossomos Humanos Y/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias/genética , Neoplasias/metabolismo
3.
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
4.
Cytogenet Genome Res ; 160(1): 18-21, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32008001

RESUMO

Multiple isodicentric Y chromosomes [idic(Y)] is a rare cytogenetic abnormality, most exclusively described in constitutional karyotypes. Only recently has this entity been reported in hematologic neoplasms such as myeloid disorders, albeit these cases remain very scarce. The possible involvement of increasing copies of potential proto-oncogenes located on the multiple idic(Y) led to consider one of them, CRLF2, as a target for kinase inhibitors. We report here, to our knowledge, the first case of multiple idic(Y) in a patient with myelofibrosis secondary to essential thrombocythemia. The patient received ruxolitinib therapy with initial good clinical response.


Assuntos
Cromossomos Humanos Y/genética , Mielofibrose Primária/complicações , Aberrações dos Cromossomos Sexuais , Trombocitemia Essencial/complicações , Idoso , Alelos , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Cariotipagem , Masculino , Mosaicismo , Contagem de Plaquetas , Mielofibrose Primária/genética , Prognóstico , Pirazóis/uso terapêutico , Receptores de Citocinas/genética , Trombocitemia Essencial/genética
5.
Braz J Med Biol Res ; 53(3): e8980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32077464

RESUMO

The mosaic 45,X/46,XY karyotype is a common sex chromosomal abnormality in infertile men. Males with this mosaic karyotype can benefit from assisted reproductive therapies, but the transmitted abnormalities contain 45,X aneuploidy as well as Y chromosome microdeletions. The aim of this study was to investigate the clinical and genetic characteristics of infertile men diagnosed with 45,X/46,XY mosaicism in China. Of the 734 infertile men found to carry chromosomal abnormalities, 14 patients were carriers of 45,X/46,XY mosaicism or its variants, giving a prevalence of 0.27% (14/5269) and accounting for 1.91% (14/734) of patients with a chromosomal abnormality. There were ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions. Case 1 and Case 4 had AZFc deletions, and the other eight cases had AZFb+c deletions. A high frequency of Y chromosome microdeletions were detected in male patients with 45,X/46,XY mosaicism. Preimplantation genetic diagnosis should be offered to men having intracytoplasmic sperm injection for hypospermatogenesis caused by 45,X/46,XY mosaicism, to avoid the risk of transfering AZF microdeletions in addition to X monosomy in male offspring.


Assuntos
Infertilidade Masculina/genética , Mosaicismo , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , China , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Aberrações dos Cromossomos Sexuais
6.
Gene ; 735: 144389, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31982552

RESUMO

Azoospermia factors, located in the long arm of the Y chromosome, are critical for spermatogenesis, the microdeletions of AZF are considered to be associated with male infertility. In addition to complete deletion, several AZFc partial deletions were also detected in infertile men with wide phenotypic heterogeneity. In this study, we investigated the relevance of Y chromosome deletions, Y-linked CNVs and variable phenotypes in infertile men. To clarify the relationship between phenotypic heterogeneity and Y chromosome deletion in male infertility, we performed chromosomal microarray analysis (CMA) capable of analyzing thousands of loci simultaneously to investigate Y-linked copy number variations (CNVs). Firstly, we reviewed the results of Y chromosome screening in 554 infertile patients and then compared the results of CMA to routine Y chromosome screening in 29 patients with Y chromosomal microdeletions. Then, the Y-linked CNVs associated with oligoasthenospermia were identified according to ACMG standards and guidelines. The results indicated that the prevalence of Yq microdeletions was 5.23% (29/554), with 93% (27/29) of the deletions in the AZFc region among 554 infertile men recruited in this study. The results of CMA and multiplex-PCR-based AZFc deletion analysis were generally concordant, but CMA provided more details about location, size and OMIM genes involved in deletion fragments of the AZF region. Of 29 clinically infertile phenotype-related CNVs detected by CMA, nine were pathogenic and the remaining 20 CNVs were OVUS. Except for a 15.69 Mb loss CNV in AZFa + b + c and an 8.25 Mb loss CNV in AZFb + c, others were located in the AZFc region. Based on a combination of the clinical symptoms and loss CNVs, we concluded that the CNV size and the involvement of spermatogenesis critical genes are two important factors that determine the relevance of a CNV in the AZFc region to the presence or absence of a clinically infertile phenotype.


Assuntos
Azoospermia/genética , Variações do Número de Cópias de DNA , Infertilidade Masculina/genética , Oligospermia/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , Azoospermia/patologia , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Infertilidade Masculina/patologia , Masculino , Oligospermia/patologia , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/patologia
7.
Nature ; 577(7792): 665-670, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31969706

RESUMO

Our knowledge of ancient human population structure in sub-Saharan Africa, particularly prior to the advent of food production, remains limited. Here we report genome-wide DNA data from four children-two of whom were buried approximately 8,000 years ago and two 3,000 years ago-from Shum Laka (Cameroon), one of the earliest known archaeological sites within the probable homeland of the Bantu language group1-11. One individual carried the deeply divergent Y chromosome haplogroup A00, which today is found almost exclusively in the same region12,13. However, the genome-wide ancestry profiles of all four individuals are most similar to those of present-day hunter-gatherers from western Central Africa, which implies that populations in western Cameroon today-as well as speakers of Bantu languages from across the continent-are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one that gave rise to at least four major lineages deep in the history of modern humans.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Africano/história , Comportamento Alimentar/etnologia , Migração Humana/história , Filogenia , Alelos , Animais , Arqueologia , Sepultamento , Camarões , Criança , Pré-Escolar , Cromossomos Humanos Y/genética , DNA Antigo/análise , Feminino , Marcadores Genéticos/genética , Genética Populacional , Genoma Humano/genética , Haplótipos/genética , História Antiga , Humanos , Idioma/história , Masculino , Pan troglodytes/genética , Análise de Componente Principal
8.
Mol Genet Genomics ; 295(3): 579-589, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31932897

RESUMO

We have determined the distribution of Y-chromosomal haplotypes and haplogroups in the Yong population, one of the largest and well-known ethnic groups that began migrating southward from China to Thailand centuries ago. Their unique mass migration pattern provided great opportunities for researchers to study the genetic links of the transboundary migration movements among the peoples of China, Myanmar and Thailand. We analysed relevant male-specific markers, such as Y-STRs and Y-SNPs, and the distribution of 23 Y-STRs of 111 Yong individuals and 116 nearby ethnic groups including the Shan, Northern Thai, Lawa, Lua, Skaw, Pwo and Padong groups. We found that the general haplogroup distribution values were similar among different populations; however, the haplogroups O1b-M268 and O2-M112 constituted the vast majority of these values. In contrast with previous maternal lineage studies, the paternal lineage of the Yong did not relate to the Xishuangbanna Dai people, who represent their historically documented ancestors. However, they did display a close genetic affinity to other prehistoric Tai-Kadai speaking groups in China such as the Zhuang and Bouyei. Low degrees of genetic admixture within the populations who belonged to the Austroasiatic and Sino-Tibetan linguistic families were observed in the gene pool of the Yong populations. Resettlement in northern Thailand in the early part of the nineteenth century AD, by way of mass migration trend, was able to preserve the Yong's ancestral genetic background in terms of the way they had previously lived in China and Myanmar. Our study has revealed similar genetic structures among ethnic populations in northern Thailand and southern China, and has identified and emphasized an ancient Tai-Kadai patrilineal ancestry line in the Yong ethnic group.


Assuntos
Cromossomos Humanos Y/genética , DNA Mitocondrial/genética , Grupos Étnicos/genética , Variação Genética , Genética Populacional , Haplótipos , Herança Paterna , Migração Humana , Humanos , Masculino , Tailândia
9.
Hum Genet ; 139(3): 401-407, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31134332

RESUMO

The extent of aneuploidy of the sex chromosomes increases with age in human leukocytes. Here, we re-explore the dynamics of normal loss of the Y chromosome (LOY) with age based on microarray data using two exponential models and two different ways to estimate the fraction of LOY. This analysis shows the existence of a significant correlation between the fraction of LOY estimated from molecular cytogenetics and genotyping microarray data. Although the specific estimates of the parameters for the two exponential models are different from those derived from cytogenetics data, the present analysis in an independent dataset of normal individuals confirms that X0 cells have a selective advantage over XY cells. Moreover, patients with age-related macular degeneration display higher fraction of LOY values and seem to have a predisposition to lose their Y chromosome even at young ages compared to control individuals. As there are no data available for the same individuals at different time points, the parameters reported here are average values drawn from population analyses.


Assuntos
Envelhecimento/genética , Cromossomos Humanos Y/genética , Degeneração Macular/genética , Aneuploidia , Deleção Cromossômica , Genótipo , Humanos , Leucócitos/fisiologia , Masculino
10.
Forensic Sci Int ; 306: 110050, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790892

RESUMO

In 1995, the historical shipwreck of La Belle was discovered off the coast of Texas. One partial human skeleton was recovered from alongside cargo in the rear portion of the ship; a second (complete) skeleton was found atop coiled anchor rope in the bow. In late 2015, comprehensive forensic genetic testing began on multiple samplings from each set of remains. For the partial skeleton recovered from the ship's rear cargo area, results were obtained for 26/27 Y-STRs using traditional CE; with MPS technology, results were obtained for 18/24 Y-STRs, 56/56 ancestry-informative SNPs (aiSNPs), 22/22 phenotype-informative SNPs (piSNPs), 22/27 autosomal STRs, 4/7 X-STRs, and 94/94 identity-informative SNPs (iiSNPs). For the complete skeleton of the second individual, results were obtained for 7/17 Y-STRs using traditional CE; with MPS technology, results were obtained for 5/24 Y-STRs, 49/56 aiSNPs, 18/22 piSNPs, 15/27 autosomal STRs, 1/7 X-STRs, and 66/94 iiSNPs. Biogeographic ancestry for each set of skeletal remains was predicted using the ancestry feature and metapopulation tool of the Y-STR Haplotype Reference Database (YHRD), Haplogroup Predictor, and the Forensic Research/Reference on Genetics knowledge base (FROG-kb). Phenotype prediction was performed using piSNP data and the HIrisplex eye color and hair color DNA phenotyping webtool. mtDNA whole genome sequencing also was performed successfully. This study highlights the sensitivity of current forensic laboratory methods in recovering DNA from historical and archaeological human remains. Using advanced sequencing technology provided by MiSeq™ FGx (Verogen) and Ion S5™ (Thermo Fisher Scientific) instrumentation, degraded skeletal remains can be characterized using a panel of diverse and highly informative markers, producing data which can be useful in both forensic and genealogical investigations.


Assuntos
Restos Mortais , Impressões Digitais de DNA , Genética Forense , Fenótipo , Navios/história , Acidentes/história , Cromossomos Humanos Y , Grupos de Populações Continentais/genética , DNA Mitocondrial/genética , Eletroforese Capilar , França , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , História do Século XVII , Humanos , Masculino , Repetições de Microssatélites , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Texas , Sequenciamento Completo do Genoma
11.
Forensic Sci Int ; 306: 110056, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765883

RESUMO

The killings during the Second World War, with nearly one hundred thousand victims, is one of the greatest losses of life in Slovenia's modern history. This article presents the genetic identification of the victims of the largest family massacre that occurred in Slovenia, in which 10 members of the same family were killed. Seven of them were buried in a hidden mass grave and only two children survived. In 2015 and 2016, two graves were found and three incomplete female skeletons and at least three incomplete male skeletons were exhumed. A total of 12 bones and teeth were analysed and compared to two living relatives. Extracted DNA was quantified using the PowerQuant kit, and various autosomal and Y-STR kits were used for STR typing. Up to 2.7 ng DNA/g of powder was acquired from the samples analysed. We managed to obtain nuclear DNA for successful STR typing from seven bones and one molar. From the female grave, autosomal profiles were obtained only from one skeleton, and from the male grave from five out of six femurs. The relationships between the males were additionally confirmed by analyses of Y-STRs. STR profiles made possible the identification of four family members; one of the aunts from the female grave, and two uncles and the father of the surviving children, who were used as family references, from the male grave. The product rule was used to calculate a combined likelihood ratio for autosomal and Y-STRs, and statistical analyses showed high confidence of correct identification with posterior probability (PP) greater than 99.9 % for three out of four victims identified. For identifying the aunt, the PP obtained after ESI-17 and NGM STR typing was too low. To increase the PP, the next-generation sequencing Precision ID GlobalFiler NGS STR Panel was used and, after the analysis of additional STR loci, the statistical analysis showed a PP greater than 99.9 %, indicating that a sufficient number of genetic markers had been investigated in identifying the skeletal remains of the aunt. An elimination database containing the genetic profiles of all individuals that had been in contact with the bones was created to ensure traceability in case of contamination, and no matches were found. After more than 70 years, the skeletal remains were returned to the surviving children, who buried their relatives in a family grave.


Assuntos
Osso e Ossos/química , Impressões Digitais de DNA , Família , Dente/química , Restos Mortais , Sepultamento , Cromossomos Humanos Y , DNA/isolamento & purificação , Exumação , Feminino , Genética Forense , Sequenciamento de Nucleotídeos em Larga Escala , História do Século XX , Humanos , Masculino , Repetições de Microssatélites , Linhagem , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Eslovênia , II Guerra Mundial
12.
BMC Evol Biol ; 19(1): 197, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675915

RESUMO

BACKGROUND: Helicobacter pylori, a bacterium that infects the human stomach, has high genetic diversity. Because its evolution is parallel to human, H. pylori is used as a tool to trace human migration. However, there are few studies about the relationship between phylogeography of H. pylori and its host human. METHODS: We examined both H. pylori DNA and the host mitochondrial DNA and Y-chromosome DNA obtained from a total 119 patients in the Dominican Republic, where human demography consists of various ancestries. DNA extracted from cultured H. pylori were analyzed by multi locus sequence typing. Mitochondrial DNA and Y-chromosome DNA were evaluated by haplogroup analyses. RESULTS: H. pylori strains were divided into 2 populations; 68 strains with African group (hpAfrica1) and 51 strains with European group (hpEurope). In Y-chromosomal haplogroup, European origin was dominant, whereas African origin was dominant both in H. pylori and in mtDNA haplogroup. These results supported the hypothesis that mother-to-child infection is predominant in H. pylori infection. The Amerindian type of mtDNA haplogroup was observed in 11.8% of the patients; however, Amerindian type (hspAmerind) of H. pylori was not observed. Although subpopulation type of most hpAfrica1 strains in Central America and South America were hybrid (hspWAfrica/hpEurope), most Dominican Republic hpAfrica1 strains were similar to those of African continent. CONCLUSIONS: Genetic features of H. pylori, mtDNA, and Y haplogroups reflect the history of colonial migration and slave trade in the Dominican Republic. Discrepancy between H. pylori and the host human genotypes support the hypothesis that adaptability of hspAmerind H. pylori strains are weaker than hpEurope strains. H. pylori strains in the Dominican Republic seem to contain larger proportion of African ancestry compared to other American continent strains.


Assuntos
Helicobacter pylori/genética , Migração Humana , Adulto , Idoso , Cromossomos Humanos Y , DNA Mitocondrial/genética , República Dominicana , Feminino , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Genética Humana , Humanos , Transmissão Vertical de Doença Infecciosa , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Filogeografia , Adulto Jovem
13.
Genome Biol ; 20(1): 207, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610793

RESUMO

BACKGROUND: Large palindromes (inverted repeats) make up substantial proportions of mammalian sex chromosomes, often contain genes, and have high rates of structural variation arising via ectopic recombination. As a result, they underlie many genomic disorders. Maintenance of the palindromic structure by gene conversion between the arms has been documented, but over longer time periods, palindromes are remarkably labile. Mechanisms of origin and loss of palindromes have, however, received little attention. RESULTS: Here, we use fiber-FISH, 10x Genomics Linked-Read sequencing, and breakpoint PCR sequencing to characterize the structural variation of the P8 palindrome on the human Y chromosome, which contains two copies of the VCY (Variable Charge Y) gene. We find a deletion of almost an entire arm of the palindrome, leading to death of the palindrome, a size increase by recruitment of adjacent sequence, and other complex changes including the formation of an entire new palindrome nearby. Together, these changes are found in ~ 1% of men, and we can assign likely molecular mechanisms to these mutational events. As a result, healthy men can have 1-4 copies of VCY. CONCLUSIONS: Gross changes, especially duplications, in palindrome structure can be relatively frequent and facilitate the evolution of sex chromosomes in humans, and potentially also in other mammalian species.


Assuntos
Cromossomos Humanos Y , Sequências Repetidas Invertidas , Proteínas Nucleares/genética , Sequência de Bases , Variações do Número de Cópias de DNA , Humanos
14.
Medicine (Baltimore) ; 98(41): e17407, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593094

RESUMO

BACKGROUND: To evaluate the safety of intracytoplasmic sperm injection (ICSI) for men with Y chromosome azoospermia factor (AZF) microdeletions. METHODS: Twenty-five men with Y chromosome microdeletions and their partners underwent ICSI treatment. These subjects were matched against 50 ICSI cycles in which the patients had normal Y chromosomes. RESULTS: Among the 25 couples, 17 achieved a clinical pregnancy of which 14 continued to a live birth. Sixteen men had deletions of AZFc markers (sY152, sY254, and sY255), 1 had a deletion of sY152, 3 had a deletion of sY254, sY255, 1 had a deletion of sY152, sY239, Sy242, sY254, and sY255, and 3 had deletions of sY152, sY254, sY255, and sY157. AZFb microdeletions (sY127, sY134, and sY143) were found in 1 patient. AZF microdeletions had no adverse effects on the clinical pregnancy, implantation or delivery rates, birth weight, gestational age, or sex ratio when compared with the control group. Overall, the multiple gestation and preterm delivery rates of the AZF microdeletion group were similar to those in the control group. CONCLUSION: Men with AZF microdeletions can achieve the delivery of healthy children using ICSI. In this series, it produced good implantation rate and obstetric and perinatal outcomes.


Assuntos
Azoospermia/terapia , Infertilidade Masculina/terapia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/terapia , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Azoospermia/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Feminino , Humanos , Recém-Nascido , Infertilidade Masculina/genética , Masculino , Gravidez , Resultado da Gravidez , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Resultado do Tratamento
15.
Nat Commun ; 10(1): 4719, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624269

RESUMO

Mosaic loss of chromosome Y (mLOY) is frequently observed in the leukocytes of ageing men. However, the genetic architecture and biological mechanisms underlying mLOY are not fully understood. In a cohort of 95,380 Japanese men, we identify 50 independent genetic markers in 46 loci associated with mLOY at a genome-wide significant level, 35 of which are unreported. Lead markers overlap enhancer marks in hematopoietic stem cells (HSCs, P ≤ 1.0 × 10-6). mLOY genome-wide association study signals exhibit polygenic architecture and demonstrate strong heritability enrichment in regions surrounding genes specifically expressed in multipotent progenitor (MPP) cells and HSCs (P ≤ 3.5 × 10-6). ChIP-seq data demonstrate that binding sites of FLI1, a fate-determining factor promoting HSC differentiation into platelets rather than red blood cells (RBCs), show a strong heritability enrichment (P = 1.5 × 10-6). Consistent with these findings, platelet and RBC counts are positively and negatively associated with mLOY, respectively. Collectively, our observations improve our understanding of the mechanisms underlying mLOY.


Assuntos
Diferenciação Celular/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Estudo de Associação Genômica Ampla/métodos , Células-Tronco Hematopoéticas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Plaquetas/citologia , Plaquetas/metabolismo , Estudos de Coortes , Eritrócitos/citologia , Eritrócitos/metabolismo , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Células-Tronco Hematopoéticas/citologia , Humanos , Japão , Masculino , Mosaicismo , Polimorfismo de Nucleotídeo Único
16.
Fa Yi Xue Za Zhi ; 35(4): 448-454, 2019 Aug.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31532156

RESUMO

Abstract: Objective To analyze the genetic phenotypes of Y-chromosome STR and SNP in Han male population of Wujiang area, Suzhou City and explore the genetic structure of population of Wujiang area for further examination of regional-specific Y-SNP genetic markers ancestor haplogroups. Methods Blood samples of 472 Wujiang area Han males were randomly collected and genotyped by YfilerTM Plus PCR Amplification Kit. The allele frequencies and haplotype frequencies of each locus were obtained using the direct calculation method. Y-SNP haplogroups of each sample were estimated using Y-Predictor software and verified through experiments by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results A total of 453 haplotypes were found in the 27 Y-STR genetic markers in 472 Han males of Wujiang area. The haplotype diversity (HD) was 0.997 696 93, among which, the highest gene diversity (GD) value was DYF387S1a/b (GD=0.953 1) and the lowest was DYS438 (GD=0.321 8). Based on genotyping data of 27 Y-STRs and 472 samples, 132 haplogroups from C, D, N, O and Q, etc downstream Y-SNP haplogroups were estimated and then verified through experiments. Conclusion This study is based on Y-chromosome STR haplotypes, and predicts Y-SNP haplogroups by Y-Predictor software, then uses ARMS-PCR to verify. Y-SNP genetic markers were introduced to achieve precise analysis of the genetic structure of male families in population of three towns in Wujiang area.


Assuntos
Cromossomos Humanos Y/genética , Genética Populacional , China , Cidades , Frequência do Gene , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único
17.
Forensic Sci Int Genet ; 43: 102139, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31487605

RESUMO

Correct identification of probative samples is the first crucial step in the analysis of sexual assault kits (SAKs). We report a nucleic acid-based approach, as an alternative to the widely utilized p30 assay, to screening male DNA from SAKs collected from female victims by combining a rapid lysis protocol with an isothermal amplification method. The enzymatic lysis protocol efficiently digests biological material to release nuclear DNA in 10 min in a single closed tube, including resilient cell types such as sperm cells. The amplification and detection of human male specific DNA is achieved through loop-mediated isothermal amplification (LAMP) accompanied with hydroxynaphthol blue, a colorimetric indicator, producing a visually-distinctive color change in the presence of male DNA. The Y-screen approach demonstrated high specificity to human male DNA, can reliably detect target DNA as low as 50 pg, and correctly identified all probative samples from 14 single-blind mock sexual assault samples. In contrast with the widely used p30 assay which requires at least 2 h incubation time and manual application to a lateral flow pad, this Y-screen assay can be completed in half the time, and can be performed in a 96-well format without the need for a fluorescence detector, making facile high-throughput sample screening possible.


Assuntos
Colorimetria , Técnicas de Amplificação de Ácido Nucleico/métodos , Espermatozoides/química , Amelogenina/genética , Cromossomos Humanos Y , DNA/análise , Marcadores Genéticos , Humanos , Indicadores e Reagentes , Masculino , Naftalenossulfonatos , Reação em Cadeia da Polimerase , Delitos Sexuais
18.
PLoS Genet ; 15(9): e1008369, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525193

RESUMO

The Y chromosome harbors nine multi-copy ampliconic gene families expressed exclusively in testis. The gene copies within each family are >99% identical to each other, which poses a major challenge in evaluating their copy number. Recent studies demonstrated high variation in Y ampliconic gene copy number among humans. However, how this variation affects expression levels in human testis remains understudied. Here we developed a novel computational tool Ampliconic Copy Number Estimator (AmpliCoNE) that utilizes read sequencing depth information to estimate Y ampliconic gene copy number per family. We applied this tool to whole-genome sequencing data of 149 men with matched testis expression data whose samples are part of the Genotype-Tissue Expression (GTEx) project. We found that the Y ampliconic gene families with low copy number in humans were deleted or pseudogenized in non-human great apes, suggesting relaxation of functional constraints. Among the Y ampliconic gene families, higher copy number leads to higher expression. Within the Y ampliconic gene families, copy number does not influence gene expression, rather a high tolerance for variation in gene expression was observed in testis of presumably healthy men. No differences in gene expression levels were found among major Y haplogroups. Age positively correlated with expression levels of the HSFY and PRY gene families in the African subhaplogroup E1b, but not in the European subhaplogroups R1b and I1. We also found that expression of five Y ampliconic gene families is coordinated with that of their non-Y (i.e. X or autosomal) homologs. Indeed, five ampliconic gene families had consistently lower expression levels when compared to their non-Y homologs suggesting dosage regulation, while the HSFY family had higher expression levels than its X homolog and thus lacked dosage regulation.


Assuntos
Cromossomos Humanos Y/genética , Genes Ligados ao Cromossomo Y/genética , Análise de Sequência de DNA/métodos , Animais , Cromossomos Humanos Y/fisiologia , Variações do Número de Cópias de DNA/genética , Bases de Dados Genéticas , Compensação de Dosagem (Genética)/genética , Compensação de Dosagem (Genética)/fisiologia , Epigênese Genética/genética , Dosagem de Genes/genética , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Genes Ligados ao Cromossomo Y/fisiologia , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Humanos , Masculino , Família Multigênica/genética , Testículo/metabolismo
19.
Forensic Sci Int Genet ; 42: 235-243, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31382158

RESUMO

Mongolians played a pivotal role in shaping the culture and genetic architecture of modern Eurasia through the rapid expansion of the Mongol Empire in the 13th century. While the historical aspects of the Mongolian Empire are well documented, research on the genetic variations among Mongolian populations is still insufficient. In this study, we examined the genetic diversity of 70 Torghut Mongols residing in the Ili region of China compared with 88 Jalaid Mongols residing 3000 km away. Over 200 forensically relevant genetic markers, including autosomal short tandem repeats (A-STRs), X chromosomal STRs (X-STRs), Y chromosomal STRs (Y-STRs), identity-informative single nucleotide polymorphisms (iiSNPs), ancestry-informative SNPs (aiSNPs), and phenotype-informative SNPs (piSNPs), were genotyped to uncover the genetic polymorphism of the Torghut Mongols. The STR genotyping results showed that 80 alleles (39 A-STRs, 25 Y-STRs, and 16 X-STRs; 14.4% of 554 alleles) identified in Torghut Mongols were not identified in Jalaid Mongols, while 155 alleles (84 A-STRs, 59 Y-STRs and 12 X-STRs; 24.6% of 630 alleles) identified in Jalaid Mongols were not observed in Torghut Mongols. Calculation of the forensic parameters demonstrated that the STRs and SNPs analyzed here could be employed in forensic applications. Interpopulation comparisons via principal component analysis (PCA), phylogenetic tree, and STRUCTURE analysis showed that the two Mongolian populations were closely related by their genetic background, although genetic differences were also discovered. When both the sequence-based A-STRs and iiSNPs were included in the STRUCTURE analysis, the Torghut population was more similar to the Uyghur population than to Jalaid Mongols, indicating certain population structure differences between the two Mongolian populations. The Y-DNA haplogroup prediction showed that although haplogroup C (C2-M217) was dominant in both Mongolian populations, haplogroup O2-M122 was rarely presented in Torghut Mongols, which differentiated the Torghut Mongols from the other Mongolian populations. This study not only uncovered the genetic features of the two Mongolian tribes, providing valuable frequency data for forensic applications, but the genetic patterns of the two Mongolian populations also provide a genetic evidence that the Torghut Mongols may have developed via the gradual intermixing of nomadic groups of Mongol and Turkic origin, as recorded in historical records. This study also highlighted the importance of building regional reference databases that consider both ethnic and geographic location information, instead of a more universal reference database, for forensic applications.


Assuntos
Grupos Étnicos/genética , Genética Populacional , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , China , Cromossomos Humanos X , Cromossomos Humanos Y , Impressões Digitais de DNA , Feminino , Genótipo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mongólia/etnologia , Análise de Componente Principal , Análise de Sequência de DNA
20.
Clin Interv Aging ; 14: 1227-1241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413553

RESUMO

Purpose: Abdominal aortic aneurysm (AAA) demonstrates many features of autoimmune diseases. Y chromosome, sex-determining region of the Y chromosome (SRY) gene, androgen receptor (AR) gene, and androgen appear as potential candidates for influence of the male immune function. This study investigated Y chromosome numbers, SRY gene, AR gene, and androgen levels in male AAAs. We also investigated the correlation between Y chromosome loss (LOY) ratio, SRY expression, androgen levels, and age. Patients and methods: We investigated LOY by fluorescence in situ hybridization (FISH) in 37 AAAs and compared with 12 patients with abdominal aortic atherosclerotic occlusive disease (AOD) and 91 healthy controls (HC). We investigated SRY and AR expression at mRNA level by real-time PCR in peripheral T lymphocytes in AAA compared with AOD and HC, and AR protein levels by immunohistochemistry (IHC) in AAA. LOY, SRY expression, androgen levels, and age were examined for correlations using the Spearman's rank correlation coefficient. Results: LOY ratio in peripheral T lymphocytes was significantly higher in the AAA group compared with the HC (9.11% vs 5.56%, P<0.001) and AOD groups (9.11% vs 6.42%, P=0.029). The SRY mRNA expression in peripheral T lymphocytes was 4.7-fold lower expressed in the AAA group than in the HC group (P<0.001). Free plasma testosterone levels were lower in the AAA group compared with the HC group (P=0.036), whereas sex hormone-binding globulin levels were higher (P=0.020). LOY ratio and expression of SRY mRNA level increased with age in the AAA group (R=0.402 and, R=0.366, respectively). A significant correlation between AR mRNA level (R=0.692) and aortic diameter was detected. Simultaneously, in AAA tissue, the rate of LOY increased with age (R=0.547) and also positively associated with LOY in peripheral blood T lymphocytes (R=0.661). Conclusion: This study identified a prominent Y chromosome loss in male AAAs, which is correlated to age, lower level of SRY expression and free testosterone, providing a new clue for the mechanisms of AAA.


Assuntos
Androgênios/sangue , Aneurisma Dissecante/epidemiologia , Aneurisma da Aorta Abdominal/epidemiologia , Cromossomos Humanos Y/fisiologia , Receptores Androgênicos/genética , Proteína da Região Y Determinante do Sexo/genética , Fatores Etários , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Aberrações dos Cromossomos Sexuais
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