Objectives: The currently available methods for rapid prenatal diagnosis of common chromosomal aneuploidies are either Interphase-Fluorescence in Situ Hybridisation (I-FISH) or Quanti- tative Fluorescent Polymerase Ch...Objectives: The currently available methods for rapid prenatal diagnosis of common chromosomal aneuploidies are either Interphase-Fluorescence in Situ Hybridisation (I-FISH) or Quanti- tative Fluorescent Polymerase Chain Reaction (QF-PCR). QF-PCR represents a rapid, high throughput, cost-effective alternative for Interphase-FISH. The objective of the study was to evaluate the performance of QF-PCR, as a molecular-based technique for the detection of chromosome 21, 18 and 13 copy numbers. Study design: A retrospective cohort of 163 samples referred for screening of common chromosomal aneuploidies was blindly tested for chromosome 21, 18 and 13 copy numbers using QF-PCR and the results were compared with those of conventional cytogenetic analysis. Results: QF-PCR demonstrated optimal sensitivity and specificity (100%) for non mosaic trisomies. QF-PCR was able to consistently detect maternal cell contamination and mosaic trisomies when the trisomic cell line was present at an adequate level (23% or more). However, QF-PCR was unable to detect chromosomal rearrangements for which the primers were not designed. Conclusion: QF- PCR proved its superior performance as a molecular-based method for autosomal aneuploidy detection concerning both sensitivity and specificity.展开更多
Objective To determine whether patients with isolated teratozoospermia have increased or decreased incidence of chromosomal aneuploidies. Methods Sperm obtained from isolated teratozoospermic men （teratozoospermic gr...Objective To determine whether patients with isolated teratozoospermia have increased or decreased incidence of chromosomal aneuploidies. Methods Sperm obtained from isolated teratozoospermic men （teratozoospermic group, n=18） and normal fertile men （the control, n=5） were analyzed using FISH （for chromosomes 18, X and Y）. Results A total of 58 178 spermatozoa were counted from the teratozoospermia group and 16 369 spermatozoa were counted from the control, with the hybridization rates of 97.5% and 98.3%, respectively. The major types of chromosomal aneuploidies were disomy （YY18, XX18, XY18, Y1818 and 3（1818） and diploidy （1818XX, 1818YY, 1818XY）. In the teratozoospermic group and the control, the disomy rates of 18 chromosome were 0.29 ±0.16% and 0.03 ±0.02%, the disomy rates of sex chromo- some were 0.65 ±0.24% and 0.05 ± 0.02%, the diploidy rates were 0.14 ± 0.12% and 0. 04±0.03%, respectively..411 the differences between these two groups were significant （P〈0. 05）.Conclusion Sperm of isolated teratozoospermic men have higher rates of 18, X and Y chromosomal aneuploidies than that of the fertile controls.展开更多
Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in...Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21,18,and 13(T21,T18,and T13);sex chromosome aneuploidies(SCAs);and subchromosomal deletions/duplications.Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test.The overall screen-positive rate of chromosomal abnormalities was 1.07%(208/19,484),including 57 cases with T21,18 cases with T18,7 cases with T13,106 cases with SCAs,and 20 cases of subchromosomal deletions/duplications.Positive predictive values were 91.30%(42/46),38.46%(5/13),33.33%(2/6),41.33%(31/75),and 27.78%(5/18),respectively.There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group(P>0.05).All of the pregnant women who had confirmed fetal T21,T18,or T13 terminated their pregnancies,except for a case of T13 mosaic,whereas 45.16%(14/31)of women with fetal SCAs continued their pregnancies.Furthermore,17 pregnant women with positive screens for T21,T18,or T13 without a subsequent diagnosis chose to terminate their pregnancy,whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21,T18,and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications.Pregnant women with fetal 47,XXX or 47,XYY were more willing to terminate their pregnancy than those with fetal 45,X or 47,XXY.展开更多
Objective:To evaluate the screening performance of noninvasive prenatal testing(NIPT)based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of Chi...Objective:To evaluate the screening performance of noninvasive prenatal testing(NIPT)based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of China.Methods:The study enrolled 26913 consecutive pregnancies,20-50 years old,who attended the Peking Union Medical College Hospital,Beijing,China,for prenatal screening from January 1,2016 to December 31,2019.Cell-free DNA was extracted from maternal peripheral blood to have a high-throughput massively parallel sequencing procedure.Cases with high-risk of fetal XXY were suggested to take invasive prenatal diagnosis(IPD)for confirmation.Maternal DNA sequencing was performed,if necessary,to find other potential factors that may lead to high-risk results of XXY by NIPT.Results:Among a cohort of 26913 pregnant women,34 were high-risk for fetal XXY,among which 30 accepted IPD while 4 declined.In those who accepted IPD,19 cases were confirmed fetal XXY by chromosome karyotyping analysis while 11 were verified as false positive.Among the 19 confirmed fetal XXY cases,14 elected pregnancy termination.For all the 34 high-risk cases,two were verified maternal sex chromosome aneuploidy.The calculated detection rate,positive predictive value,and false-positive rate of NIPT for fetal XXY in this cohort was 100.00%(19/19),63.33%(19/30),and 0.04%(11/26890),respectively.And the percentage of pregnancy termination was 73.68%(14/19).Conclusion:NIPT could be used as a potential method for fetal XXY screening,although the accuracy needs to be improved.As NIPT is not diagnostic,IPD is strongly recommended for those with high-risk results.For cases with discordance between NIPT and fetal karyotyping,maternal DNA sequencing would help to identify the cause of false-positive/false-negative results.展开更多
In the past 9 years,several externally blinded validation and implementation studies have shown that it is now possible,through analysis of cell-free(cf)DNA in maternal blood,to effectively detect a high proportion of...In the past 9 years,several externally blinded validation and implementation studies have shown that it is now possible,through analysis of cell-free(cf)DNA in maternal blood,to effectively detect a high proportion of fetuses affected by trisomies 21,18,and 13 at a much lower false positive rate than all other existing screening methods.This article aims to review the technical and clinical considerations for implementing cfDNA testing in routine practice,including methods of analysis,performance of the test,models for clinical implementation,and interpretation of results.展开更多
Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery ...Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.展开更多
Alzheimer disease(AD)is a complex neurodegenerative pathology that is characterized by a cognitive decline.Its causes and mechanisms are still largely unknown.It has been suggested that both genetic and life exposure ...Alzheimer disease(AD)is a complex neurodegenerative pathology that is characterized by a cognitive decline.Its causes and mechanisms are still largely unknown.It has been suggested that both genetic and life exposure factors can contribute to AD development.There are also evidences that chromosomal alterations can be related to this disease.So far,there is not a precise diagnosis for AD,which is given only after the exclusion of other dementia by clinical and neurological examination.The possible association of AD with chromosomal alterations and the easy access of classical cytogenetics analysis are important aspects to consider,given the difficulties in diagnosis.Due to the lack of similar studies in Brazil and the increasing number of AD cases in the state of Amazonas,the aim of this study was to investigate the presence of chromosomal alterations in patients diagnosed with AD in Manaus,Amazonas,Brazil.Peripheral blood lymphocytes of twelve patients and twelve healthy individuals with the same age were analyzed using conventional karyotyping.All AD patients presented cells with autosomal aneuploidy,while no chromosomal alterations were found in the age-matched controls.Also,rare events of double and multiple aneuploidies are being reported in association with AD for the first time.Our results corroborate that the increase in the frequencies of aneuploidies is not related to the aging process itself,but it might be associated to the disease development.However,no chromosomes were preferentially affected in all AD patients,and no consistent karyotype pattern for AD lymphocytes was found.Therefore,our results do not support the use of standard cytogenetics as a tool for AD diagnosis.Future studies are necessary to understand better the association between chromosomal alterations and AD.展开更多
AIM： To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TPS3 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H...AIM： To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TPS3 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. METHODS： Gastric biopsies from normal mucosa （NM, n = 10）, chronic gastritis （CG, n = 38）, atrophic gastritis （CAG, n=13） and gastric ulcer （GU, n=21） were studied using fluorescence in situ hybridization （FISH） and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect Hpylori. An association of the gastric pathologies and aneuploidies with Hpylori infection was assessed. RESULTS： Aneuploidies were increasingly found from CG （21%） to CAG （31%） and to GU （62%）, involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG （P=0.0143） and GU （P=0.0498）. No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% （5/11） and 12% （2/17） of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. CONCLUSION： The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with Hpylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa.展开更多
One of the main causes of pregnancy failure and fetus abortion is oocyte aneuploidy,which is increased with maternal aging.Numerous possible causes of oocyte aneuploidy in aged women have been proposed,including cross...One of the main causes of pregnancy failure and fetus abortion is oocyte aneuploidy,which is increased with maternal aging.Numerous possible causes of oocyte aneuploidy in aged women have been proposed,including cross-over formation defect,cohesin loss,spindle deformation,spindle assembly checkpoint malfunction,microtubule-kinetochore attachment failure,kinetochore mis-orientation,mitochondria dysfunction-induced increases in reactive oxygen species,protein over-acetylation,and DNA damage.However,it still needs to be answered if these aneuploidization factors have inherent relations,and how to prevent chromosome aneuploidy in aged oocytes.Epidemiologically,oocyte aneuploidy has been found to be weakly associated with higher homocysteine concentrations,obesity,ionizing radiation and even seasonality.In this review,we summarize the research progress and present an integrated view of oocyte aneuploidization.展开更多
Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain large...Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.展开更多
AIM:To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esopha-geal squamous precancerous lesions.METHODS:This study was designed as a population-based screening study.A total of 5...AIM:To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esopha-geal squamous precancerous lesions.METHODS:This study was designed as a population-based screening study.A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong.However,only 452 subjects had results of liquid-based cytology,DNA-ICM and pathology.The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse.RESULTS:Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%,86.36%,79.55% and 77.27%,respectively,which were better than that of liquid-based cytology (75%).Specifici-ties of DNA-ICM were 70.83%,84.07%,92.65% and 96.81%,but the specificity of liquid-based cytology was 91.91%.The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%,respectively.CONCLUSION:It is possible to use DNA-ICM tech-nique as a primary screening method for esophageal squamous precancerous lesions.展开更多
Objective:Hematogenous metastasis is essential for the progression of ovarian cancer(OC),and circulating tumor cells(CTCs)are part of the metastatic cascade.However,the detection rate of CTC is low due to the use of l...Objective:Hematogenous metastasis is essential for the progression of ovarian cancer(OC),and circulating tumor cells(CTCs)are part of the metastatic cascade.However,the detection rate of CTC is low due to the use of less sensitive detection methods.Therefore,this study aimed to detect CTCs and circulating tumorigenic endothelial cells(CTECs)in patients with OC using subtraction enrichment and immunostaining and fluorescence in situ hybridization(SE-iFISH).Methods:We enrolled a total of 56 subjects,including 20 OC patients and 36 ovarian benign tumor patients.CTCs and CTECs were captured by subtraction enrichment(SE)and counted and classified according to immunofluorescence staining of tumor markers(TMs)carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)combined with fluorescence in situ hybridization(iFISH)of chromosome 8(Chr8)aneuploidy.The diagnostic value and subtype characteristics of CTCs and CTECs were investigated.Results:The detection rate of CTCs by SE-iFISH was high.Compared with CA125 and HE4,Chr8 aneuploidy was the major identification feature of CTC.CTC counts in OC were statistically higher than those in benign groups.CTC and CTEC with≥pentaploidy were detected in both groups,illustrating the poor diagnostic value of CTC or CTEC.Distributions of triploid and tetraploid CTC subtypes were significantly different,and combined detection of triploid and tetraploid CTCs showed the best diagnostic value.In contrast,the distribution of CTECs in the OC and benign groups had no statistically significant difference.Small CTCs accounted for over 1/3 of the total CTC count.We also found that small CTCs and CTECs primarily comprised triploid cells,while large CTCs and CTECs mainly comprised pentaploidy and beyond.Conclusions:The application of SE-iFISH offered a more comprehensive understanding of heterogeneous CTCs and CTECs in OC.Analysis of subclass characteristics of the CTCs and CTECs according to Chr8 aneuploidy and cell size may broaden their potential clinical utility and deepen mechanistic studies in OC.展开更多
Conventional PCR methods combined with linkage analysis based on short tandem repeats （STRs） or Karyomapping with single nucleotide polymorphism （SNP） arrays, have been applied to preimplantation genetic diagnosis...Conventional PCR methods combined with linkage analysis based on short tandem repeats （STRs） or Karyomapping with single nucleotide polymorphism （SNP） arrays, have been applied to preimplantation genetic diagnosis （PGD） for spinal muscular atrophy （SMA）, an autosome recessive disorder. However, it has limitations in SMA diagnosis by Karyomapping, and these methods are unable to distinguish wild- type embryos with carriers effectively. Mutated allele revealed by sequencing with aneuploidy and linkage analyses （MARSALA） is a new method allowing embryo selection by a one-step next-generation sequencing （NGS） procedure, which has been applied in PGD for both autosome dominant and X-linked diseases in our group previously. In this study, we carried out PGD based on MARSALA for two carrier families with SMA affected children. As a result, one of the couples has given birth to a healthy baby free of mutations in SMA-causing gene. It is the first time that MARSALA was applied to PGD for SMA, and we can distinguish the embryos with heterozygous deletion （carriers） from the wild-type （normal） ones accurately through this NGS-based method. In addition, direct mutation detection allows us to identify the affected embryos （homozygous deletion）, which can be regarded as probands for linkage analysis, in case that the affected family member is absent, In the future, the NGS-based MARSALA method is expected to be used in PGD for all monogenetic disorders with known pathogenic gene mutation.展开更多
AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. MET...AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immu- nostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneu- ploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level ofchromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal- type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic path- ways.展开更多
Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed...Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.展开更多
Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re rel...Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re relative global gene expression in diffe rent types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression.While previously available methods require a selective examination of specific genes,RNA sequencing provides a whole-genome view of gene expression in aneuploids.Most studies of global aneuploidy effects have concentrated on individual types of aneuploids because multiple dose aneuploidies of the same genomic region are difficult to produce in most model genetic organisms.The genetic toolkit of maize allows the examination of multiple ploidies and 1-4 doses of chromosome arms.Thus,a detailed examination of expression changes both on the varied chromosome arms and elsewhere in the genome is possible,in both hypoploids and hyperploids,compared with euploid controls.Previous studies observed the inverse trans effect,in which genes not varied in DNA dosage were expressed in a negative relationship to the varied chromosomal region.This response was also the major type of changes found globally in this study.Many genes varied in dosage showed proportional expression changes,though some were seen to be partly or fully dosage compensated.It was also found that the effects of aneuploidy were progressive,with more severe aneuploids producing effects of greater magnitude.展开更多
The objective of this study was to investigate whether medical therapy can reduce sperm aneuploidy levels and irfiprove the results of intracytoplasmic sperm injection （ICSI） in patients with severe idiopathic oligo...The objective of this study was to investigate whether medical therapy can reduce sperm aneuploidy levels and irfiprove the results of intracytoplasmic sperm injection （ICSI） in patients with severe idiopathic oligoasthenoteratospermia （OAT）. Thirty-three infertile couples requiring ICSI because of severe idiopathic OAT after at least one unsuccessful ICSI cycle were considered. Semen parameters （concentration, motility and morphology）, the percentage of aneuploid sperm and the results of ICSI （the number of oocytes fertilized, embryos transferred, biochemical pregnancies, clinical pregnancies and live births） were compared before and after a 3-month course of treatment with L-carnitine 1 g given twice per day＋acetyI-L-carnitine 500 mg given twice per day＋one 30-mg cinnoxicam tablet every 4 days. Aneuploidy was assessed using fluorescent in situ hybridisation （FISH） performed on chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22. The results showed that 22 of the 33 patients had a reduced frequency of aneuploid sperm and improved sperm morphology after treatment （group 1）, and 11 showed no change （group 2）. The numbers of biochemical pregnancies, clinical pregnancies and live births were significantly higher in group I than in group 2. No significant difference was found between the groups regarding the numbers of oocytes fertilized and embryos transferred. The side effects were negligible. The numbers of ICSI pregnancies and live births in severe idiopathic OAT patients improved with a course of L-carnitine, acetyI-L-carnitine and cinnoxicam.展开更多
AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohi...AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.展开更多
Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segre...Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segregation and promote genetic diversity of progenies.Crossover patterns are tightly controlled and exhibit three characteristics:obligatory crossover,crossover interference,and crossover homeostasis.Aberrant crossover patterns are the leading cause of infertility,miscarriage,and congenital disease.Crossover recombination occurs in the context of meiotic chromosomes,and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally.Meiotic chromosomes are organized in a loop-axis architecture.Diverse evidence shows that chromosome axis length determines crossover frequency.Interestingly,short chromosomes show different crossover patterns compared to long chromosomes.A high frequency of human embryos are aneuploid,primarily derived from female meiosis errors.Dramatically increased aneuploidy in older women is the well-known“maternal age effect.”However,a high frequency of aneuploidy also occurs in young women,derived from crossover maturation inefficiency in human females.In addition,frequency of human aneuploidy also shows other age-dependent alterations.Here,current advances in the understanding of these issues are reviewed,regulation of crossover patterns by meiotic chromosomes are discussed,and issues that remain to be investigated are suggested.展开更多
基金a DAAD-German Egyptian Research Long-Term Schoolarship(GERLS).
文摘Objectives: The currently available methods for rapid prenatal diagnosis of common chromosomal aneuploidies are either Interphase-Fluorescence in Situ Hybridisation (I-FISH) or Quanti- tative Fluorescent Polymerase Chain Reaction (QF-PCR). QF-PCR represents a rapid, high throughput, cost-effective alternative for Interphase-FISH. The objective of the study was to evaluate the performance of QF-PCR, as a molecular-based technique for the detection of chromosome 21, 18 and 13 copy numbers. Study design: A retrospective cohort of 163 samples referred for screening of common chromosomal aneuploidies was blindly tested for chromosome 21, 18 and 13 copy numbers using QF-PCR and the results were compared with those of conventional cytogenetic analysis. Results: QF-PCR demonstrated optimal sensitivity and specificity (100%) for non mosaic trisomies. QF-PCR was able to consistently detect maternal cell contamination and mosaic trisomies when the trisomic cell line was present at an adequate level (23% or more). However, QF-PCR was unable to detect chromosomal rearrangements for which the primers were not designed. Conclusion: QF- PCR proved its superior performance as a molecular-based method for autosomal aneuploidy detection concerning both sensitivity and specificity.
基金funded by the Key Project of Jiangxi Provincial Department of Public Health, No. 20104010
文摘Objective To determine whether patients with isolated teratozoospermia have increased or decreased incidence of chromosomal aneuploidies. Methods Sperm obtained from isolated teratozoospermic men （teratozoospermic group, n=18） and normal fertile men （the control, n=5） were analyzed using FISH （for chromosomes 18, X and Y）. Results A total of 58 178 spermatozoa were counted from the teratozoospermia group and 16 369 spermatozoa were counted from the control, with the hybridization rates of 97.5% and 98.3%, respectively. The major types of chromosomal aneuploidies were disomy （YY18, XX18, XY18, Y1818 and 3（1818） and diploidy （1818XX, 1818YY, 1818XY）. In the teratozoospermic group and the control, the disomy rates of 18 chromosome were 0.29 ±0.16% and 0.03 ±0.02%, the disomy rates of sex chromo- some were 0.65 ±0.24% and 0.05 ± 0.02%, the diploidy rates were 0.14 ± 0.12% and 0. 04±0.03%, respectively..411 the differences between these two groups were significant （P〈0. 05）.Conclusion Sperm of isolated teratozoospermic men have higher rates of 18, X and Y chromosomal aneuploidies than that of the fertile controls.
基金supported by the Shanghai Municipal Health Bureau(grants 20174Y0199 and 201740096)Shanghai Clinical and Medical Center of Key Programs(2017ZZ01016)。
文摘Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21,18,and 13(T21,T18,and T13);sex chromosome aneuploidies(SCAs);and subchromosomal deletions/duplications.Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test.The overall screen-positive rate of chromosomal abnormalities was 1.07%(208/19,484),including 57 cases with T21,18 cases with T18,7 cases with T13,106 cases with SCAs,and 20 cases of subchromosomal deletions/duplications.Positive predictive values were 91.30%(42/46),38.46%(5/13),33.33%(2/6),41.33%(31/75),and 27.78%(5/18),respectively.There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group(P>0.05).All of the pregnant women who had confirmed fetal T21,T18,or T13 terminated their pregnancies,except for a case of T13 mosaic,whereas 45.16%(14/31)of women with fetal SCAs continued their pregnancies.Furthermore,17 pregnant women with positive screens for T21,T18,or T13 without a subsequent diagnosis chose to terminate their pregnancy,whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21,T18,and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications.Pregnant women with fetal 47,XXX or 47,XYY were more willing to terminate their pregnancy than those with fetal 45,X or 47,XXY.
文摘Objective:To evaluate the screening performance of noninvasive prenatal testing(NIPT)based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of China.Methods:The study enrolled 26913 consecutive pregnancies,20-50 years old,who attended the Peking Union Medical College Hospital,Beijing,China,for prenatal screening from January 1,2016 to December 31,2019.Cell-free DNA was extracted from maternal peripheral blood to have a high-throughput massively parallel sequencing procedure.Cases with high-risk of fetal XXY were suggested to take invasive prenatal diagnosis(IPD)for confirmation.Maternal DNA sequencing was performed,if necessary,to find other potential factors that may lead to high-risk results of XXY by NIPT.Results:Among a cohort of 26913 pregnant women,34 were high-risk for fetal XXY,among which 30 accepted IPD while 4 declined.In those who accepted IPD,19 cases were confirmed fetal XXY by chromosome karyotyping analysis while 11 were verified as false positive.Among the 19 confirmed fetal XXY cases,14 elected pregnancy termination.For all the 34 high-risk cases,two were verified maternal sex chromosome aneuploidy.The calculated detection rate,positive predictive value,and false-positive rate of NIPT for fetal XXY in this cohort was 100.00%(19/19),63.33%(19/30),and 0.04%(11/26890),respectively.And the percentage of pregnancy termination was 73.68%(14/19).Conclusion:NIPT could be used as a potential method for fetal XXY screening,although the accuracy needs to be improved.As NIPT is not diagnostic,IPD is strongly recommended for those with high-risk results.For cases with discordance between NIPT and fetal karyotyping,maternal DNA sequencing would help to identify the cause of false-positive/false-negative results.
文摘In the past 9 years,several externally blinded validation and implementation studies have shown that it is now possible,through analysis of cell-free(cf)DNA in maternal blood,to effectively detect a high proportion of fetuses affected by trisomies 21,18,and 13 at a much lower false positive rate than all other existing screening methods.This article aims to review the technical and clinical considerations for implementing cfDNA testing in routine practice,including methods of analysis,performance of the test,models for clinical implementation,and interpretation of results.
文摘Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.
文摘Alzheimer disease(AD)is a complex neurodegenerative pathology that is characterized by a cognitive decline.Its causes and mechanisms are still largely unknown.It has been suggested that both genetic and life exposure factors can contribute to AD development.There are also evidences that chromosomal alterations can be related to this disease.So far,there is not a precise diagnosis for AD,which is given only after the exclusion of other dementia by clinical and neurological examination.The possible association of AD with chromosomal alterations and the easy access of classical cytogenetics analysis are important aspects to consider,given the difficulties in diagnosis.Due to the lack of similar studies in Brazil and the increasing number of AD cases in the state of Amazonas,the aim of this study was to investigate the presence of chromosomal alterations in patients diagnosed with AD in Manaus,Amazonas,Brazil.Peripheral blood lymphocytes of twelve patients and twelve healthy individuals with the same age were analyzed using conventional karyotyping.All AD patients presented cells with autosomal aneuploidy,while no chromosomal alterations were found in the age-matched controls.Also,rare events of double and multiple aneuploidies are being reported in association with AD for the first time.Our results corroborate that the increase in the frequencies of aneuploidies is not related to the aging process itself,but it might be associated to the disease development.However,no chromosomes were preferentially affected in all AD patients,and no consistent karyotype pattern for AD lymphocytes was found.Therefore,our results do not support the use of standard cytogenetics as a tool for AD diagnosis.Future studies are necessary to understand better the association between chromosomal alterations and AD.
基金Supported by the Brazilian Agency FAPESP,No.00/09413-6
文摘AIM： To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TPS3 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. METHODS： Gastric biopsies from normal mucosa （NM, n = 10）, chronic gastritis （CG, n = 38）, atrophic gastritis （CAG, n=13） and gastric ulcer （GU, n=21） were studied using fluorescence in situ hybridization （FISH） and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect Hpylori. An association of the gastric pathologies and aneuploidies with Hpylori infection was assessed. RESULTS： Aneuploidies were increasingly found from CG （21%） to CAG （31%） and to GU （62%）, involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG （P=0.0143） and GU （P=0.0498）. No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% （5/11） and 12% （2/17） of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. CONCLUSION： The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with Hpylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa.
基金supported by the National Natural Science Foundation of China(31801245,81671425 and 81971357)Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2019GZR110104001)
文摘One of the main causes of pregnancy failure and fetus abortion is oocyte aneuploidy,which is increased with maternal aging.Numerous possible causes of oocyte aneuploidy in aged women have been proposed,including cross-over formation defect,cohesin loss,spindle deformation,spindle assembly checkpoint malfunction,microtubule-kinetochore attachment failure,kinetochore mis-orientation,mitochondria dysfunction-induced increases in reactive oxygen species,protein over-acetylation,and DNA damage.However,it still needs to be answered if these aneuploidization factors have inherent relations,and how to prevent chromosome aneuploidy in aged oocytes.Epidemiologically,oocyte aneuploidy has been found to be weakly associated with higher homocysteine concentrations,obesity,ionizing radiation and even seasonality.In this review,we summarize the research progress and present an integrated view of oocyte aneuploidization.
文摘Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.
基金Supported by Grants from the Ministry of Health of China,No.200902002-8Grants from Cancer Institute/Hospital Chinese Academy of Medical Sciences and Peking Union Medical College,No.2009YF50
文摘AIM:To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esopha-geal squamous precancerous lesions.METHODS:This study was designed as a population-based screening study.A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong.However,only 452 subjects had results of liquid-based cytology,DNA-ICM and pathology.The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse.RESULTS:Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%,86.36%,79.55% and 77.27%,respectively,which were better than that of liquid-based cytology (75%).Specifici-ties of DNA-ICM were 70.83%,84.07%,92.65% and 96.81%,but the specificity of liquid-based cytology was 91.91%.The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%,respectively.CONCLUSION:It is possible to use DNA-ICM tech-nique as a primary screening method for esophageal squamous precancerous lesions.
基金financially supported by the National Key Research and Development Program of China(No.2016YFA0201404)National Natural Science Foundation of China(No.81971360)the National Key Technology R&D Program of China(No.2015BAI 13B06)。
文摘Objective:Hematogenous metastasis is essential for the progression of ovarian cancer(OC),and circulating tumor cells(CTCs)are part of the metastatic cascade.However,the detection rate of CTC is low due to the use of less sensitive detection methods.Therefore,this study aimed to detect CTCs and circulating tumorigenic endothelial cells(CTECs)in patients with OC using subtraction enrichment and immunostaining and fluorescence in situ hybridization(SE-iFISH).Methods:We enrolled a total of 56 subjects,including 20 OC patients and 36 ovarian benign tumor patients.CTCs and CTECs were captured by subtraction enrichment(SE)and counted and classified according to immunofluorescence staining of tumor markers(TMs)carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)combined with fluorescence in situ hybridization(iFISH)of chromosome 8(Chr8)aneuploidy.The diagnostic value and subtype characteristics of CTCs and CTECs were investigated.Results:The detection rate of CTCs by SE-iFISH was high.Compared with CA125 and HE4,Chr8 aneuploidy was the major identification feature of CTC.CTC counts in OC were statistically higher than those in benign groups.CTC and CTEC with≥pentaploidy were detected in both groups,illustrating the poor diagnostic value of CTC or CTEC.Distributions of triploid and tetraploid CTC subtypes were significantly different,and combined detection of triploid and tetraploid CTCs showed the best diagnostic value.In contrast,the distribution of CTECs in the OC and benign groups had no statistically significant difference.Small CTCs accounted for over 1/3 of the total CTC count.We also found that small CTCs and CTECs primarily comprised triploid cells,while large CTCs and CTECs mainly comprised pentaploidy and beyond.Conclusions:The application of SE-iFISH offered a more comprehensive understanding of heterogeneous CTCs and CTECs in OC.Analysis of subclass characteristics of the CTCs and CTECs according to Chr8 aneuploidy and cell size may broaden their potential clinical utility and deepen mechanistic studies in OC.
基金supported by the National Natural Science Foundation of China (Nos. 31522034, 31571544 and 31230047)the National High Technology Research and Development Program (No. 2015AA020407)+1 种基金Beijing Municipal Science and Technology Commission (No. D151100002415004)Research Fund of National Health and Family Planning Commission of China (No. 201402004)
文摘Conventional PCR methods combined with linkage analysis based on short tandem repeats （STRs） or Karyomapping with single nucleotide polymorphism （SNP） arrays, have been applied to preimplantation genetic diagnosis （PGD） for spinal muscular atrophy （SMA）, an autosome recessive disorder. However, it has limitations in SMA diagnosis by Karyomapping, and these methods are unable to distinguish wild- type embryos with carriers effectively. Mutated allele revealed by sequencing with aneuploidy and linkage analyses （MARSALA） is a new method allowing embryo selection by a one-step next-generation sequencing （NGS） procedure, which has been applied in PGD for both autosome dominant and X-linked diseases in our group previously. In this study, we carried out PGD based on MARSALA for two carrier families with SMA affected children. As a result, one of the couples has given birth to a healthy baby free of mutations in SMA-causing gene. It is the first time that MARSALA was applied to PGD for SMA, and we can distinguish the embryos with heterozygous deletion （carriers） from the wild-type （normal） ones accurately through this NGS-based method. In addition, direct mutation detection allows us to identify the affected embryos （homozygous deletion）, which can be regarded as probands for linkage analysis, in case that the affected family member is absent, In the future, the NGS-based MARSALA method is expected to be used in PGD for all monogenetic disorders with known pathogenic gene mutation.
基金Supported by Financiadora de Estudos e Projetos(FINEP CT-INFRA/FADESP),No.0927-03Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP)No.2003/06540-5+1 种基金DQC had a master fellowship,No.151127/2002-6granted by Coordenacao de Aperfeicoamento de Pessoal de Nível Superior
文摘AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immu- nostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneu- ploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level ofchromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal- type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic path- ways.
基金supported by Chinese National Natural Science Foundation (No. 81301323, 81472789)Beijing Natural Science Foundation (No. 7161002)the Capital Health Research and Development of Special (No. 2016-1-1021)
文摘Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.
基金This work was supported by the National Science Foundation grants IOS-1545780,NSF 1615789,and NSF 1853556。
文摘Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re relative global gene expression in diffe rent types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression.While previously available methods require a selective examination of specific genes,RNA sequencing provides a whole-genome view of gene expression in aneuploids.Most studies of global aneuploidy effects have concentrated on individual types of aneuploids because multiple dose aneuploidies of the same genomic region are difficult to produce in most model genetic organisms.The genetic toolkit of maize allows the examination of multiple ploidies and 1-4 doses of chromosome arms.Thus,a detailed examination of expression changes both on the varied chromosome arms and elsewhere in the genome is possible,in both hypoploids and hyperploids,compared with euploid controls.Previous studies observed the inverse trans effect,in which genes not varied in DNA dosage were expressed in a negative relationship to the varied chromosomal region.This response was also the major type of changes found globally in this study.Many genes varied in dosage showed proportional expression changes,though some were seen to be partly or fully dosage compensated.It was also found that the effects of aneuploidy were progressive,with more severe aneuploids producing effects of greater magnitude.
文摘The objective of this study was to investigate whether medical therapy can reduce sperm aneuploidy levels and irfiprove the results of intracytoplasmic sperm injection （ICSI） in patients with severe idiopathic oligoasthenoteratospermia （OAT）. Thirty-three infertile couples requiring ICSI because of severe idiopathic OAT after at least one unsuccessful ICSI cycle were considered. Semen parameters （concentration, motility and morphology）, the percentage of aneuploid sperm and the results of ICSI （the number of oocytes fertilized, embryos transferred, biochemical pregnancies, clinical pregnancies and live births） were compared before and after a 3-month course of treatment with L-carnitine 1 g given twice per day＋acetyI-L-carnitine 500 mg given twice per day＋one 30-mg cinnoxicam tablet every 4 days. Aneuploidy was assessed using fluorescent in situ hybridisation （FISH） performed on chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22. The results showed that 22 of the 33 patients had a reduced frequency of aneuploid sperm and improved sperm morphology after treatment （group 1）, and 11 showed no change （group 2）. The numbers of biochemical pregnancies, clinical pregnancies and live births were significantly higher in group I than in group 2. No significant difference was found between the groups regarding the numbers of oocytes fertilized and embryos transferred. The side effects were negligible. The numbers of ICSI pregnancies and live births in severe idiopathic OAT patients improved with a course of L-carnitine, acetyI-L-carnitine and cinnoxicam.
文摘AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.
基金This work is supported by grants from the National Key R&D Program of China(2018YFC1003700,2018YFC1003400)National Natural Science Foundation of China(31671293,31801203,and 31890782).
文摘Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segregation and promote genetic diversity of progenies.Crossover patterns are tightly controlled and exhibit three characteristics:obligatory crossover,crossover interference,and crossover homeostasis.Aberrant crossover patterns are the leading cause of infertility,miscarriage,and congenital disease.Crossover recombination occurs in the context of meiotic chromosomes,and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally.Meiotic chromosomes are organized in a loop-axis architecture.Diverse evidence shows that chromosome axis length determines crossover frequency.Interestingly,short chromosomes show different crossover patterns compared to long chromosomes.A high frequency of human embryos are aneuploid,primarily derived from female meiosis errors.Dramatically increased aneuploidy in older women is the well-known“maternal age effect.”However,a high frequency of aneuploidy also occurs in young women,derived from crossover maturation inefficiency in human females.In addition,frequency of human aneuploidy also shows other age-dependent alterations.Here,current advances in the understanding of these issues are reviewed,regulation of crossover patterns by meiotic chromosomes are discussed,and issues that remain to be investigated are suggested.
