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1.
Opt Express ; 30(26): 47338-47349, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36558664

RESUMEN

The resonant optical tunneling effect (ROTE) originates from the frustrated total reflection effect because unique transmission characteristics are used to study high-sensitivity sensors. In this study, we theoretically demonstrated that choosing a suitable transmission gap made it possible for the ROTE structure based on hexagonal boron nitride and graphene to obtain a large Goos-Hänchen shift as high as tens of thousands of times the incident wavelength at a specific incident angle. The amplitude of the Goos-Hänchen shift was found to be sensitive to the central layer thickness but was also modulated by the tunneling gap on both sides. In addition, adjusting the chemical potential and relaxation time of the graphene sheets could alter the Goos-Hänchen shift. Our work provides a new way to explore the Goos-Hänchen effect and opens the possibility for the application of high-precision measurement technology based on the ROTE.

2.
Opt Express ; 30(21): 37888-37898, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36258368

RESUMEN

In this study, a one-dimensional (1D) two-material period ring optical waveguide network (TMPROWN) was designed, and its optical properties were investigated. The key characteristics observed in the 1D TMPROWN include the following: (1) Bound states in continuum (BICs) can be generated in the optical waveguide network. (2) In contrast to the BICs previously reported in optical structures, the range of the BICs generated by the 1D TMPROWN is not only larger, but also continuous. This feature makes it possible for us to further study the electromagnetic wave characteristics in the range of the BICs. In addition, we analyzed the physical mechanisms of the BICs generated in the 1D TMPROWN. The 1D TMPROWN is simple in structure, demonstrates flexibility with respect to adjusting the frequency band of the BICs, and offers easy measurement of the amplitude and phase of electromagnetic waves. Hence, further research on high-power super luminescent diodes, optical switches, efficient photonic energy storage, and other optical devices based on the 1D TMPROWN designed in this study is likely to have implications in a broad range of applications.

3.
J Obstet Gynaecol Res ; 47(3): 865-872, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33372274

RESUMEN

AIM: To investigate the epidemiology of chromosomal abnormalities (CA) in fetuses of all pregnancies based on a provincial-wide birth defects-monitoring system, which could provide scientific basis for making relatively policy and research. METHODS: Chromosomal abnormalities cases were collected from all hospitals in Hunan Province, China, between 2016 and 2019. The prevalence of CAs was calculated to examine associations among infant sex, maternal age and region. The rates of prenatal diagnosis and termination of pregnancy (TOP) involving CA or associated anomalies were calculated as rates or proportions. RESULTS: From 2016 to 2019, a total of 2 883 890 perinatal infants (28 weeks of gestation to postpartum 7 days) underwent prenatal screening and diagnostic tests, and 3181 fetuses were diagnosed as CA, with the prevalence of 11.03/10 000. The average prevalence of CAs was higher for male than female fetuses (11.33/10 000 vs 10.06/10 000) (OR = 1.13, 95% CI: 1.05-1.21), which was higher in urban areas than rural areas (23.03/10 000 vs 7.13/10 000) (OR = 3.23, 95% CI: 3.02-3.47), and the prevalence increased linearly with maternal age ( X trend 2 = 1821.844, P = 0.000). Among the fetuses with CAs, 3097 (97.36%) were diagnosed prenatally, and 3046 (98.35%) underwent TOP. The majority of CA were numerical abnormalities (90.18%). The main types of numerical autosomal abnormalities were trisomy 21 (6.69/10 000, 59.57%), trisomy 18 (1.13/10 000, 10.04%) and trisomy 13 (0.21/10 000, 1.88%). The main types of numerical gonosomal abnormalities were Klinefelter syndrome (0.68/10 000, 6.02%), Turner syndrome (0.49/10 000, 4.39%), Triple X syndrome (0.26/10 000, 2.29%) and 47,XYY syndrome (0.21/10 000, 1.91%). The three associated anomalies with the highest proportions were congenital heart defects (CHD) (41.06%), cleft palate or/and cleft lip (10.89%) and congenital talipes equinovarus (8.94%). CONCLUSION: The prevalence of CA was lower than that reported. Chromosome detection should be further promoted including test contest and coverage, especially for urban areas, older mothers and fetuses with CHD, cleft palate or/and cleft lip or congenital talipes equinovarus.


Asunto(s)
Aberraciones Cromosómicas , Diagnóstico Prenatal , China/epidemiología , Femenino , Humanos , Masculino , Embarazo , Prevalencia , Trisomía , Ultrasonografía Prenatal
4.
Plant Biotechnol J ; 18(4): 955-968, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31549477

RESUMEN

Complete and highly accurate reference genomes and gene annotations are indispensable for basic biological research and trait improvement of woody tree species. In this study, we integrated single-molecule sequencing and high-throughput chromosome conformation capture techniques to produce a high-quality and long-range contiguity chromosome-scale genome assembly of the soft-seeded pomegranate cultivar 'Tunisia'. The genome covers 320.31 Mb (scaffold N50 = 39.96 Mb; contig N50 = 4.49 Mb) and includes 33 594 protein-coding genes. We also resequenced 26 pomegranate varieties that varied regarding seed hardness. Comparative genomic analyses revealed many genetic differences between soft- and hard-seeded pomegranate varieties. A set of selective loci containing SUC8-like, SUC6, FoxO and MAPK were identified by the selective sweep analysis between hard- and soft-seeded populations. An exceptionally large selective region (26.2 Mb) was identified on chromosome 1. Our assembled pomegranate genome is more complete than other currently available genome assemblies. Our results indicate that genomic variations and selective genes may have contributed to the genetic divergence between soft- and hard-seeded pomegranate varieties.


Asunto(s)
Genoma de Planta , Granada (Fruta)/genética , Semillas , Cromosomas de las Plantas , Variación Genética , Dureza
5.
Prenat Diagn ; 40(8): 925-930, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31955435

RESUMEN

OBJECTIVE: The aim of this study was to analyse the characteristics of the prenatal diagnosis (PD) of birth defects (BDs) and termination of pregnancy (TOP) for fetal anomalies and to suggest perinatal management. METHODS: BD surveillance data were collected from 52 registered hospitals in Hunan between 2015 and 2018. The PD and TOP rates of BDs were calculated to examine the associations between infant sex, maternal age, and region. RESULTS: From 2015 to 2018, a total of 18 931 fetuses with BDs were identified, of which 10 299 fetuses (54.4%) were diagnosed prenatally and 9343 pregnancies (90.7% among PDs and 49.3% among BDs) were terminated. The mean gestational age at diagnosis for fetuses with BDs was 25.1 ± 5.9 weeks and showed a downward trend over the study period. The average PD rate of the BDs was higher in rural areas than in urban areas (58.1% vs 50.3%), higher for female than male fetuses (57.25% vs 48.92%), and higher for mothers older than age 35 than for those younger (58.62% vs 53.69%). The average TOP rate of fetuses with BDs in rural areas was higher than that in urban areas (91.99% vs 89.12%) and decreased with increasing maternal age ( x trend 2 = 7.926, P = .005). The five BDs with the highest PD rates were conjoined twins (100%), anencephaly (97.87%), congenital hydrocephalus (97.66%), chromosomal malformation (96.07%), and encephalocele (95.54%). The five BDs with the highest TOP rates among the PDs were conjoined twins (100%), exstrophy of the urinary bladder (100%), chromosomal malformation (98.09%), encephalocele (98%), and anencephaly (97.28%). CONCLUSIONS: More than half of BDs were diagnosed prenatally, with the majority diagnosed at less than 28 gestational weeks. The TOP rates following PD in Hunan Province were high, especially for rural and younger mothers. The findings suggest a need for high-quality, targeted counselling following PD.


Asunto(s)
Aborto Eugénico/estadística & datos numéricos , Anomalías Congénitas/diagnóstico , Diagnóstico Prenatal , Aborto Inducido/estadística & datos numéricos , Adulto , China/epidemiología , Anomalías Congénitas/epidemiología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Edad Materna , Embarazo , Resultado del Embarazo/epidemiología , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/estadística & datos numéricos , Prevalencia , Adulto Joven
6.
Int J Mol Sci ; 21(18)2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32927615

RESUMEN

Sucrose, an important sugar, is transported from source to sink tissues through the phloem, and plays important role in the development of important traits in plants. However, the SUT gene family is still not well characterized in pomegranate. In this study, we first identified the pomegranate sucrose transporter (SUT) gene family from the whole genome. Then, the phylogenetic relationship of SUT genes, gene structure and their promoters were analyzed. Additionally, their expression patterns were detected during the development of the seed. Lastly, genetic transformation and cytological observation were used to study the function of PgL0145810.1. A total of ten pomegranate SUT genes were identified from the whole genome of pomegranate 'Tunisia'. The promoter region of all the pomegranate SUT genes contained myeloblastosis (MYB) elements. Four of the SUT genes, PgL0328370.1, PgL0099690.1, PgL0145810.1 and PgL0145770.1, were differentially expressed during seed development. We further noticed that PgL0145810.1 was expressed most prominently in the stem parts in transgenic plants compared to other tissue parts (leaves, flowers and silique). The cells in the xylem vessels were small and lignin content was lower in the transgenic plants as compared to wild Arabidopsis plants. In general, our result suggests that the MYB cis-elements in the promoter region might regulate PgL0145810.1 expression to control the structure of xylem, thereby affecting seed hardness in pomegranate.


Asunto(s)
Proteínas de Transporte de Membrana/genética , Proteínas de Plantas/genética , Granada (Fruta)/genética , Semillas/genética , Familia de Multigenes , Fenotipo , Plantas Modificadas Genéticamente , Granada (Fruta)/crecimiento & desarrollo , Semillas/crecimiento & desarrollo
7.
Int J Mol Sci ; 21(2)2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31952315

RESUMEN

Female sterility is a key factor restricting plant reproduction. Our previous studies have revealed that pomegranate female sterility mainly arose from the abnormality of ovule development. MicroRNAs (miRNAs) play important roles in ovule development. However, little is known about the roles of miRNAs in female sterility. In this study, a combined high-throughput sequencing approach was used to investigate the miRNAs and their targeted transcripts involved in female development. A total of 103 conserved and 58 novel miRNAs were identified. Comparative profiling indicated that the expression of 43 known miRNAs and 14 novel miRNAs were differentially expressed between functional male flowers (FMFs) and bisexual flowers (BFs), 30 known miRNAs and nine novel miRNAs showed significant differences among different stages of BFs, and 20 known miRNAs and 18 novel miRNAs exhibited remarkable expression differences among different stages of FMFs. Gene ontology (GO) analyses of 144 predicted targets of differentially expressed miRNAs indicated that the "reproduction process" and "floral whorl development" processes were significantly enriched. The miRNA-mRNA interaction analyses revealed six pairs of candidate miRNAs and their targets associated with female sterility. Interestingly, pg-miR166a-3p was accumulated, whereas its predicted targets (Gglean012177.1 and Gglean013966.1) were repressed in functional male flowers (FMFs), and the interaction between pg-miR166a-3p and its targets (Gglean012177.1 and Gglean013966.1) were confirmed by transient assay. A. thaliana transformed with 35S-pre-pg-miR166a-3p verified the role of pg-miR166a-3p in ovule development, which indicated pg-miR166a-3p's potential role in pomegranate female sterility. The results provide new insights into molecular mechanisms underlying the female sterility at the miRNA level.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , MicroARNs/genética , Infertilidad Vegetal/genética , Granada (Fruta)/genética , ARN Mensajero/genética , ARN de Planta/genética , ARN Pequeño no Traducido/genética , Análisis por Conglomerados , Flores/genética , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Redes Reguladoras de Genes , Genes de Plantas/genética , Óvulo Vegetal/genética , Reproducción/genética
8.
BMC Med Genet ; 17(1): 77, 2016 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-27821076

RESUMEN

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder characterized by gastrointestinal (GI) hamartomatous polyps, mucocutaneous hyperpigmentation, and an increased risk of cancer. Mutations in the serine-threonine kinase 11 gene (SKT11) are the major cause of PJS. CASE PRESENTATION: Blood samples were collected from six PJS families including eight patients. Mutation screening of STK11 gene was performed in these six families by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay. Three novel mutations (c.721G > C, c.645_726del82, and del(exon2-5)) and three recurrent mutations (c.752G > A, c.545 T > C and del(exon1)) in STK11 were detected in six Chinese PJS families. Genotype-phenotype correlations suggested that truncating mutations trend to result in severe complications. CONCLUSION: These findings broaden the mutation spectrum of the STK11 gene and would help clinicians and genetic counselors provide better clinical surveillance for PJS patients, especially for ones carrying truncating mutation.


Asunto(s)
Mutación , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinasas/genética , Análisis de Secuencia de ADN/métodos , Quinasas de la Proteína-Quinasa Activada por el AMP , Adolescente , Adulto , Pueblo Asiatico/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Linaje , Adulto Joven
9.
Am J Med Genet A ; 170(6): 1613-21, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27028180

RESUMEN

Kabuki syndrome (KS) is a rare condition with multiple congenital anomalies and mental retardation. Exonic deletions, disrupting the lysine (K)-specific demethylase 6A (KDM6A) gene have been demonstrated as rare cause of KS. Here, we report a de novo 227-kb deletion in chromosome Xp11.3 of a 7-year-old Chinese girl with KS. Besides the symptoms of KS, the patient also presented with skin allergic manifestations, which were considered to be a new, rare feature of the phenotypic spectrum. The deletion includes the upstream region and exons 1-2 of KDM6A and potentially causes haploinsuffiency of the gene. We also discuss the mutation spectrum of KDM6A and clinical variability of patients with KDM6A deletion through a literature review. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Exones , Cara/anomalías , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/genética , Histona Demetilasas/genética , Proteínas Nucleares/genética , Eliminación de Secuencia , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/genética , China , Análisis Mutacional de ADN , Facies , Femenino , Genes Ligados a X , Estudios de Asociación Genética , Estudio de Asociación del Genoma Completo , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Polimorfismo de Nucleótido Simple , Inactivación del Cromosoma X
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(5): 606-9, 2016 Oct.
Artículo en Zh | MEDLINE | ID: mdl-27577204

RESUMEN

OBJECTIVE: To study the pattern of CGG repeat instability within germline cells derived from two male fetuses affected with Fragile X syndrome (FXS). METHODS: The length and methylation status of CGG repeats within the testes of a fetus carrying a full FXS mutation and another fetus carrying mosaicism FXS mutation were analyzed with Southern blotting and AmplideX FMR1 PCR. Immunohistochemistry was also applied for the measurement of FMR1 protein (FMRP) expression within the testes. RESULTS: For the fetus carrying the full mutation, Southern blotting analysis of the PCR product has detected an expected band representing the full mutation in its brain and a premutation band of > 160 CGG repeats in its testis. Whereas the pattern of premutation/full mutation in mosaic testis was similar to that in peripheral blood and no sign of contracted fragment was found other than a band of about 160 CGG repeats. Immunohistochemistry assay with a FMRP-specific antibody demonstrated a number of FMRP-positive germ cells, which suggested a contraction from full mutation to premutation alleles. CONCLUSION: This study has clarified the instability pattern of CGG repeat and expression of FMRP protein within the testes of fetuses affected with FXS, confirming that the CGG repeat can contract progressively within the germline. The FMRP expression in the testis is consistent with spermatogonium proliferation, and thus the contraction from full mutation to unmethylated premutations may occur for the requirement of FMRP expression during spermatogenesis. The better understanding of FMRP function during germ cell proliferation may elucidate the mechanism underlying the contraction of full FXS mutation in male germline.


Asunto(s)
Feto/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Espermatozoides/metabolismo , Expansión de Repetición de Trinucleótido/genética , Aborto Eugénico , Southern Blotting , Encéfalo/embriología , Encéfalo/metabolismo , Metilación de ADN , Resultado Fatal , Feto/citología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/diagnóstico , Humanos , Inmunohistoquímica , Masculino , Mosaicismo , Mutación , Reacción en Cadena de la Polimerasa , Testículo/citología , Testículo/embriología , Testículo/metabolismo
11.
Clin Chem ; 61(1): 172-81, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25376582

RESUMEN

BACKGROUND: Noninvasive prenatal testing (NIPT) for monogenic diseases by use of PCR-based strategies requires precise quantification of mutant fetal alleles circulating in the maternal plasma. The study describes the development and validation of a novel assay termed circulating single-molecule amplification and resequencing technology (cSMART) for counting single allelic molecules in plasma. Here we demonstrate the suitability of cSMART for NIPT, with Wilson Disease (WD) as proof of concept. METHODS: We used Sanger and whole-exome sequencing to identify familial ATP7B (ATPase, Cu(++) transporting, ß polypeptide) gene mutations. For cSMART, single molecules were tagged with unique barcodes and circularized, and alleles were targeted and replicated by inverse PCR. The unique single allelic molecules were identified by sequencing and counted, and the percentage of mutant alleles in the original maternal plasma sample was used to determine fetal genotypes. RESULTS: Four families with WD pedigrees consented to the study. Using Sanger and whole-exome sequencing, we mapped the pathogenic ATP7B mutations in each pedigree and confirmed the proband's original diagnosis of WD. After validation of cSMART with defined plasma models mimicking fetal inheritance of paternal, maternal, or both parental mutant alleles, we retrospectively showed in second pregnancies that the fetal genotypes assigned by invasive testing and NIPT were concordant. CONCLUSIONS: We developed a reliable and accurate NIPT assay that correctly diagnosed the fetal genotypes in 4 pregnancies at risk for WD. This novel technology has potential as a universal strategy for NIPT of other monogenic disorders, since it requires only knowledge of the parental pathogenic mutations.


Asunto(s)
Análisis Mutacional de ADN/métodos , ADN , Degeneración Hepatolenticular/sangre , Degeneración Hepatolenticular/genética , Técnicas de Diagnóstico Molecular/métodos , Diagnóstico Prenatal/métodos , Adenosina Trifosfatasas/genética , Alelos , Proteínas de Transporte de Catión/genética , ATPasas Transportadoras de Cobre , ADN/sangre , ADN/genética , Sondas de ADN , Femenino , Edad Gestacional , Degeneración Hepatolenticular/embriología , Heterocigoto , Homocigoto , Humanos , Masculino , Técnicas de Diagnóstico Molecular/instrumentación , Embarazo , Diagnóstico Prenatal/instrumentación
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 31(6): 708-12, 2014 Dec.
Artículo en Zh | MEDLINE | ID: mdl-25449072

RESUMEN

OBJECTIVE: To investigate the genotype-phenotype correlation in patients with Angelman syndrome/Prader-Willi syndrome (AS/PWS) and assess the application value of high-resolution single nucleotide polymorphism microarrays (SNP array) for such diseases. METHODS: Twelve AS/PWS patients were diagnosed through SNP array, fluorescence in situ hybridization (FISH) and karyotype analysis. Clinical characteristics were analyzed. RESULTS: Deletions ranging from 4.8 Mb to 7.0 Mb on chromosome 15q11.2-13 were detected in 11 patients. Uniparental disomy (UPD) was detected in only 1 patient. Patients with deletions could be divided into 2 groups, including 7 cases with class I and 4 with class II. The two groups however had no significant phenotypic difference. The UPD patient had relatively better development and language ability. Deletions of 6 patients were confirmed by FISH to be of de novo in origin. The risk to their sibs was determined to be less than 1%. CONCLUSION: The phenotypic differences between AS/PWS patients with class I and class II deletion need to be further studied. SNP array is useful in detecting and distinguishing of patients with deletion or UPD. This method may be applied for studying the genotype-phenotype association and the mechanism underlying AS/PWS.


Asunto(s)
Síndrome de Angelman/genética , Síndrome de Prader-Willi/genética , Síndrome de Angelman/diagnóstico , Preescolar , Deleción Cromosómica , Femenino , Genotipo , Humanos , Lactante , Cariotipificación , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Síndrome de Prader-Willi/diagnóstico
14.
Chin Med J (Engl) ; 137(3): 294-302, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37874032

RESUMEN

BACKGROUND: The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019. METHODS: The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored. RESULTS: The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3-0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, -1.0 to -0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07-0.35; P = 0.003) with regard to incident cases in 2019. CONCLUSIONS: Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.


Asunto(s)
Neoplasias Endometriales , Carga Global de Enfermedades , Humanos , Femenino , Incidencia , Neoplasias Endometriales/epidemiología , Costo de Enfermedad
15.
Eur J Med Genet ; 67: 104909, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199457

RESUMEN

BACKGROUND: The 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines articulates that the effects of certain types of variants on gene function can often be seen as a complete absence of the gene product by leading to a lack of transcription or nonsense-mediated decay(NMD). However, detailed information considering different types of loss of function(LOF) variants, refined steps assimilating details concerning location of variant, changes in strength levels, NMD boundary, or any additional information pointing to a true null effect, were all left to expert judgement. As part of its Clinical Genome Resource (ClinGen) initiative, Variant Curation Expert Panels (VCEPs) are designated to make gene/disease-centric specifications in accordance with the ACMG/AMP guidelines, including a more detailed definition of what constitutes an appropriate LOF evidence. Our goal was to evaluate the current LOF guidelines developed by the VCEPs and analyse the prior curated variants concerning the PVS1 criteria, bringing people occupied in genetic data analysis a comprehensive understanding of this code. METHODS: Our study evaluated 7 VCEPs for their LOF criteria (PVS1). Subsequently, we assessed the predictive criteria by considering the underlying disease mechanism, protein transcript, and variant types delineated. Then, we meticulously curated the LOF evidence referenced by each VCEP in their preliminary variant classification, thereby scrutinizing the recommendations put forth by VCEPs and their application in the interpretation of the aforementioned predictive criteria. Based on these, an extensive curation of evidence summary considering PVS1 applied by VCEPs according to their classification of pilot variants for the purpose of analyzing VCEP criteria specifications and their use in the understanding of LOF was conducted. RESULTS: We observed in this article that the VCEPs discussed followed the majority of Sequence Variant Interpretation (SVI) recommendations concerning the application of this LOF criteria, except for some disease/gene specific considerations. We highlighted the wide range of PVS1 strength levels approved by VCEP, reflecting the diversity of evidence for each variants type. In addition, we observed substantial differences in the approach used to determine relative strengths for different types of null variants and in the attitude towards these principles concerning variant location, NMD and influence to protein function between VCEPs. CONCLUSIONS: It is difficult to understand the intricacies of the predictive data(PVS1), which often requires expert-level knowledge of disease/gene. The VCEP criteria specifications for the predictive evidence play an important role in making it more accessible for the curators to apply the predictive data by providing details concerning this complex criteria. Despite this, we believe there is a need for more guidance on standardizing this process and ensuring consistency in the application of this predictive evidence.


Asunto(s)
Variación Genética , Genoma Humano , Humanos , Genómica , Fenotipo , Pruebas Genéticas
16.
Prenat Diagn ; 33(5): 409-15, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23299662

RESUMEN

OBJECTIVE: To determine whether non-invasive prenatal testing by maternal plasma DNA sequencing can uncover all fetal chromosome aneuploidies in one simple sequencing event. METHODS: Plasma samples from 435 pregnant women at high risk for Down syndrome were collected prior to amniocentesis in three hospitals in China between March 2009 and June 2011. We sequenced the plasma DNA extracted from these samples at low coverage. We discovered that the genome representation of each of the 24 chromosomes obeyed a linear relationship to its GC content. Applying this relationship, we analysed the copy number of each of the 24 chromosomes. Full fetal karyotyping was compared with maternal plasma DNA sequencing results. RESULTS: Among the 435 samples, 412 samples (94.7%) have full karyotyping and sequencing results. Sixty-seven samples containing a fetal chromosome aneuploidy, including trisomy 21, trisomy 18, trisomy 13, trisomy 9, monosomy X or others, can be accurately identified with a detection sensitivity of 100% and a detection specificity of 99.71%. Normalization of the chromosome representation values against chromosomal guanine/cytosine base content is the key issue to ensure the accuracy. CONCLUSIONS: Our results indicate that non-invasive detection of fetal chromosome aneuploidies for all 24 chromosomes in one single sequencing event is feasible.


Asunto(s)
Aneuploidia , Trastornos de los Cromosomas/diagnóstico , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Diagnóstico Prenatal/métodos , Adulto , Amniocentesis , China/epidemiología , Trastornos de los Cromosomas/epidemiología , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 9/genética , Síndrome de Down/diagnóstico , Femenino , Feto , Humanos , Cariotipificación/métodos , Embarazo , Diagnóstico Prenatal/estadística & datos numéricos , Trisomía/diagnóstico , Trisomía/genética
17.
J Ovarian Res ; 16(1): 139, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452315

RESUMEN

BACKGROUND: The specific long-term trend in ovarian cancer (OC) rates in China has been rarely investigated. We aimed to estimate the temporal trends in incidence and mortality rates from 1990 to 2019 in OC and predict the next 30-year levels. Data on the incidence, mortality rates, and the number of new cases and deaths cases due to OC in the China cohort from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019. Temporal trends in incidence and mortality rates were evaluated by joinpoint regression models. The incidence and mortality rates and the estimated number of cases from 2020 to 2049 were predicted using the Bayesian age-period-cohort model. RESULTS: Consecutive increasing trends in age-standardized incidence (average annual percent change [AAPC] = 2.03; 95% confidence interval [CI], 1.90-2.16; p < 0.001) and mortality (AAPC = 1.58; 95% CI, 1.38-1.78; p < 0.001) rates in OC were observed from 1990-2019 in China. Theoretically, both the estimated age-standardized (per 100,000 women) incidence (from 4.77 in 2019 to 8.95 in 2049) and mortality (from 2.88 in 2019 to 4.03 in 2049) rates will continue to increase substantially in the coming 30 years. And the estimated number of new cases of, and deaths from OC will increase by more than 3 times between 2019 and 2049. CONCLUSIONS: The disease burden of OC in incidence and mortality has been increasing in China over the past 30 years and will be predicted to increase continuously in the coming three decades.


Asunto(s)
Neoplasias Ováricas , Adulto , Femenino , Humanos , Teorema de Bayes , China/epidemiología , Incidencia , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/mortalidad , Predicción/métodos , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años
18.
Clin Chim Acta ; 551: 117619, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38375625

RESUMEN

Thalassemia is one of the most widely distributed monogenic disorders in the world and affects the largest number of people. It can manifest a wide spectrum of phenotypes from asymptomatic to fatal, which is associated with the degree of imbalance between α- and ß-globin chains. Therefore, individuals with different genotypes could present with a similar phenotype. Genetic analysis is always needed to make a correct diagnosis. However, routine genetic analysis of thalassemia used in the Chinese population identifies only 23 common variants, resulting in many cases undiagnosed or being misdiagnosed. In this study, we applied a long-read sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) to 30 subjects whose hematologic screening results could not be explained by the routine genetic test results. The identification of additional variants and the correction of genotypes allowed the interpretation of the clinical phenotype in 24 subjects, which have been confirmed to be correct by independent experiments. Moreover, we identified a novel 8.4-kb deletion containing the entire HBB and HBD genes as well as part of the HBBP1 gene, expanding the genotype spectrum of ß-thalassemia. CATSA showed a great advantage over other genetic tests in the diagnosis of thalassemia caused by rare variants.


Asunto(s)
Talasemia , Talasemia alfa , Talasemia beta , Humanos , Alelos , Talasemia/diagnóstico , Talasemia/genética , Genotipo , Fenotipo , Talasemia beta/diagnóstico , Talasemia beta/genética , Tecnología , Proteínas Portadoras/genética , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Talasemia alfa/epidemiología , Mutación
19.
Front Cell Neurosci ; 16: 996379, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36106011

RESUMEN

Drug abuse is considered a maladaptive pathology of emotional memory and is associated with craving and relapse induced by drug-associated stimuli or drugs. Reconsolidation is an independent memory process with a strict time window followed by the reactivation of drug-associated stimulus depending on the basolateral amygdala (BLA). Pharmacology or behavior treatment that disrupts the reconsolidation can effectively attenuate drug-seeking in addicts. Here, we hypothesized that heroin-memory reconsolidation requires cAMP-dependent protein kinase A (PKA) of BLA based on the fundamental effect of PKA in synaptic plasticity and memory process. After 10 days of acquisition, the rats underwent 11 days of extinction training and then received the intra-BLA infusions of the PKA inhibitor Rp-cAMPS at different time windows with/without a reactivation session. The results show that PKA inhibitor treatment in the reconsolidation time window disrupts the reconsolidation and consequently reduces cue-induced reinstatement, heroin-induced reinstatement, and spontaneous recovery of heroin-seeking behavior in the rats. In contrast, there was no effect on cue-induced reinstatement in the intra-BLA infusion of PKA inhibitor 6 h after reactivation or without reactivation. These data suggest that PKA inhibition disrupts the reconsolidation of heroin-associated memory, reduces subsequent drug seeking, and prevents relapse, which is retrieval-dependent, time-limited, and BLA-dependent.

20.
Nanomaterials (Basel) ; 11(9)2021 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-34578673

RESUMEN

Quasi-bound states in the continuum provide an effective and observable way to improve metasurface performance, usually with an ultra-high-quality factor. Dielectric metasurfaces dependent on Mie resonances have the characteristic of significantly low loss, and the polarization can be affected by the parameter tuning of the structure. Based on the theory of quasi-bound states in the continuum, we propose and simulate a bifunctional resonant metasurface, whose periodic unit structure consists of four antiparallel and symmetrical amorphous silicon columns embedded in a poly(methyl methacrylate) layer. The metasurface can exhibit an extreme Huygens' regime in the case of an incident plane wave with linear polarization, while exhibiting chirality in the case of incident circular polarized light. Our structure provides ideas for promoting the multifunctional development of flat optical devices, as well as presenting potential in polarization-dependent fields.

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