ABSTRACT
OBJECTIVE@#To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area.@*METHODS@#A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test.@*RESULTS@#19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia.@*CONCLUSION@#CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.
Subject(s)
Humans , Male , Azoospermia/genetics , DNA Copy Number Variations , Oligospermia/genetics , Infertility, Male/genetics , Y ChromosomeABSTRACT
OBJECTIVE@#To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion.@*METHODS@#A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing (NIPT) at Tianjin Medical University General Hospital in July 2021 was selected as the study subject. Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), real-time fluorescence PCR (QF-PCR), and ultrasound examination.@*RESULTS@#Analysis of the amniocytes at 23 gestational weeks had yielded a 45,X karyotype. However, FISH had shown signals of Y chromosome. Re-examination by cordocentesis had shown a mosaicism of 46,X,+mar[33]/45,X[17]. FISH showed that 69% of the cells had contained Y chromosome signals. The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos) chrY: g.13200001_ 28820000del (mosaicism rate = 64%), which suggested mosaicism for a Yq deletion, which encompassed the azoospermia factor (AZF) region. Deletion of the AZF region was verified by QF-PCR. The fetal karyotype was ultimately determined as mos46,X,del(Y)(q11.1)[33]/45,X[17]. Although ultrasound examination had shown no abnormality in the fetus, the couple had opted to terminate the pregnancy, and the induced fetus had a normal male appearance.@*CONCLUSION@#The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis. For fetuses with mosaicism chromosomal abnormalities, it may be difficult to accurately predict the postnatal phenotype. It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.
Subject(s)
Female , Pregnancy , Male , Humans , Mosaicism , DNA Copy Number Variations , In Situ Hybridization, Fluorescence , Y Chromosome , FetusABSTRACT
OBJECTIVE@#To explore the genetic basis for a rare case with Disorder of sex development.@*METHODS@#Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out.@*RESULTS@#The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223).@*CONCLUSION@#The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
Subject(s)
Female , Humans , Adolescent , DNA Copy Number Variations , In Situ Hybridization, Fluorescence , Y Chromosome , Sexual Development , MosaicismABSTRACT
The paternal inheritance characteristics of Y chromosome have been widely used in the forensic genetics field to detect the genetic markers in the non-recombining block, and used in the studies such as, genetic relationship identification, mixed stain detection, pedigree screen and ethnicity determination. At present, capillary electrophoresis is still the most common detection technology. The commercial detection kits and data analysis and processing system based on this technology are very mature. However, the disadvantages of traditional detection technology have gradually appeared with the rapid growth of bio-information amount, which promotes the renewal of forensic DNA typing technology. In recent years, next generation sequencing (NGS) technology has developed rapidly. This technology has been applied to various fields including forensic genetics and has provided new techniques for the detection of Y chromosome genetic markers. This article describes the current situation and application prospects of the NGS technology in forensic Y chromosome genetic markers detection in order to provide new ideas for future judicial practice.
Subject(s)
Humans , Chromosomes, Human, Y/genetics , DNA Fingerprinting , Forensic Genetics , Genetic Markers , High-Throughput Nucleotide Sequencing , Microsatellite Repeats , Technology , Y ChromosomeABSTRACT
Subject(s)
Female , Humans , Male , Bone Marrow , Diagnosis , Fluorescence , In Situ Hybridization , Korea , Leukemia , Leukemia, Promyelocytic, Acute , Microsatellite Repeats , Peripheral Blood Stem Cell Transplantation , Polymorphism, Single Nucleotide , Stem Cell Transplantation , Tandem Repeat Sequences , Tissue Donors , Y ChromosomeABSTRACT
@#45,X/46,XY mosaicism is a rare disorder with a wide heterogeneity in its manifestations. An 18-year-old girl was referred to the endocrine clinic for investigation of her primary amenorrhea. Clinical examination was unremarkable. Hormonal profile was consistent with primary ovarian insufficiency and human chorionic gonadotropin (hCG) stimulation did not show evidence of active testicular tissue. Karyotyping studies by G-banding revealed a 45,X/46,XY karyotype. She was diagnosed with mosaic Turner syndrome with Y chromosomal material and investigation was performed to identify the presence of male gonads due to the risk of gonadal malignancy. Magnetic resonance imaging (MRI) of the pelvis did not show evidence of gonads. Laparoscopic exploration was proposed but the patient and parents refused opting for conservative management. This case highlights the challenges in the management of this rare condition.
Subject(s)
Gonadal Dysgenesis, Mixed , Turner Syndrome , Y ChromosomeABSTRACT
ABSTRACT Purpose: To identify the fetal stem cell (FSC) response to maternal renal injury with emphasis on renal integrity improvement and Y chromosome detection in damaged maternal kidney. Materials and Methods: Eight non-green fluorescent protein (GFP) transgenic Sprague-Dawley rats were mated with GFP-positive transgenic male rats. Renal damage was induced on the right kidney at gestational day 11. The same procedure was performed in eight non-pregnant rats as control group. Three months after delivery, right ne- phrectomy was performed in order to evaluate the injured kidney. The fresh perfused kidneys were stained with anti-GFP antibody. Polymerase chain reaction (PCR) assay was also performed for the Y chromosome detection. Cell culture was performed to detect the GFP-positive cells. Technetium-99m-DMSA renal scan and single-photon emission computed tomography (SPECT) were performed after renal damage induction and 3 months later to evaluate the improvement of renal integrity. Results: The presence of FSCs was confirmed by immune histochemical staining as well as immunofluorescent imaging of the damaged part. Gradient PCR of female rat purified DNA demonstrated the presence of Y-chromosome in the damaged maternal kidney. Moreover, the culture of kidney cells showed GPF- positive cells by immuno- fluorescence microscopy. The acute renal scar was repaired and the integrity of dam- aged kidney reached to near normal levels in experimental group as shown in DMSA scan. However, no significant improvement was observed in control group. Conclusion: FSC seems to be the main mechanism in repairing of the maternal renal injury during pregnancy as indicated by Y chromosome and GFP-positive cells in the sub-cultured medium.
Subject(s)
Animals , Male , Female , Pregnancy , Wound Healing/physiology , Chimerism , Fetal Stem Cells/physiology , Kidney Diseases/physiopathology , Maternal-Fetal Exchange/physiology , Time Factors , Y Chromosome , Immunohistochemistry , Tomography, Emission-Computed, Single-Photon , Cells, Cultured , Polymerase Chain Reaction , Fluorescent Antibody Technique , Rats, Sprague-Dawley , Radiopharmaceuticals , Technetium Tc 99m Dimercaptosuccinic Acid , Disease Models, Animal , Kidney Diseases/pathology , Kidney Diseases/diagnostic imagingABSTRACT
We report the case of a 46-year-old Chinese male patient who visited our clinic complaining of infertility. Semen analysis revealed azoospermia, and azoospermia factor c region partial deletion (b1/b3) was detected using Y chromosome microdeletion analysis. Testicular sperm extraction was performed after genetic counseling. The bilateral ductus deferens and a portion of the epididymis were absent, whereas the remaining epididymis was expanded. Motile intratesticular spermatozoa were successfully extracted from the seminiferous tubule. On histopathology, nearly complete spermatogenesis was confirmed in almost every seminiferous tubule. To our knowledge, this is the first case report of b1/b3 deletion with a congenital bilateral absence of the vas deferens and almost normal spermatogenesis.
Subject(s)
Humans , Male , Middle Aged , Asian People , Azoospermia , Epididymis , Genetic Counseling , Infertility , Infertility, Male , Semen Analysis , Seminiferous Tubules , Spermatogenesis , Spermatozoa , Vas Deferens , Y ChromosomeABSTRACT
BACKGROUND: Chromosomal abnormalities are confirmed as one of the frequent causes of male infertility. The microdeletion of the azoospermia factor (AZF) region in the Y chromosome was discovered as another frequent genetic cause associated with male infertility. The aim of this study was to evaluate the frequency and type of chromosomal abnormalities and Y chromosome microdeletions in Korean infertile men. METHODS: A total of 846 infertile men with azoospermia and severe oligozoospermia were included for genetic screening. Cytogenetic analyses using G-banding and screening for Y chromosome microdeletions by multiplex PCR for AZF genes were performed. RESULTS: Chromosomal abnormalities were detected in 112 infertile men (13.2%). Of these, Klinefelter's syndrome was the most common (55.4%, 62/112), followed by balanced translocation including translocation between sex chromosome and autosome (14.3%), Yq deletion (13.4%), X/XY mosaicism with Yq deletion (12.5%), and XX male (4.5%). The overall prevalence of Y chromosome microdeletions was 9.2% (78/846). Most microdeletions were in the AZFc region (51.3%) with a low incidence in AZFa (7.7 %) and AZFb (6.4 %). Combined deletions involving the AZFbc and AZFabc regions were detected in 26.9 % and 7.7 % of men, respectively. Among the infertile men with Y chromosome microdeletions, the incidence of chromosomal abnormality was 25.6% (20/78). CONCLUSIONS: There was a high incidence (20.1%) of chromosomal abnormalities and Y chromosome microdeletions in Korean infertile men. These findings strongly suggest that genetic screening for chromosomal abnormalities and Y chromosome microdeletions should be performed, and genetic counseling should be provided before starting assisted reproductive techniques.
Subject(s)
Humans , Male , Azoospermia , Chromosome Aberrations , Cytogenetic Analysis , Genetic Counseling , Genetic Testing , Incidence , Infertility, Male , Klinefelter Syndrome , Mass Screening , Mosaicism , Multiplex Polymerase Chain Reaction , Oligospermia , Prevalence , Reproductive Techniques, Assisted , Sex Chromosomes , Y ChromosomeABSTRACT
Interchromosomal insertion of Y chromosome heterochromatin in an autosome was identified in a fetus and a family. A fetal karyotype was analyzed as 46,XX,dup(7)(?q22q21.1) in a referred amniocentesis at 16 weeks of gestation for advanced maternal age. In the familial karyotype analyses for identification of der(7), the mother, the first daughter and the maternal grandmother showed the same der(7) as the fetus's. CBG-banding was positive at 7q22 region of der(7) that indicated inserted material was originated from heterochromatin. The origin of heterochromatic insertion region in der(7) of the fetus and the mother was found in Yq12 region by fluorescent in situ hybridization with a DYZ1 probe. In the specific analysis of Y chromosomal heterochromatic region of ins(7;Y) of the mother, 15 sequence tagged sites from Yp11.3 region including SRY to Yq11.223 region was not detected. Final karyotypes of the mother, the first daughter and the maternal grandmother were reported as 46,XX,der(7)ins(7;Y)(q21.3;q12q12). All female carriers of ins(7;Y) in the family showed normal phenotype and the mother and the maternal grandmother were fertile. A healthy girl was born at term. We report a rare case of familial interchromosomal insertion of Y chromosome heterochromatin detected only in female family members with normal phenotype that was diagnosed prenatally.
Subject(s)
Female , Humans , Pregnancy , Amniocentesis , Fetus , Grandparents , Heterochromatin , In Situ Hybridization, Fluorescence , Karyotype , Maternal Age , Mothers , Nuclear Family , Phenotype , Prenatal Diagnosis , Sequence Tagged Sites , Y ChromosomeABSTRACT
A 15-year-old boy was referred due to gynecomastia and short stature. He was overweight and showed the knuckle-dimple sign on the left hand, a short fourth toe on the left foot, and male external genitalia with a small phallus. His levels of estradiol and follicle-stimulating hormone were increased, and his testosterone concentration was normal. Other hormonal tests were within the normal range. Radiographs showed short fourth and fifth metacarpals and fourth metatarsal bones. The karyotype was reported as 46,X,+mar, and the marker chromosome was shown to originate from the Y chromosome, which was identified by fluorescence in situ hybridization. Polymerase chain reaction and direct sequencing were used to clarify the deleted loci of the Y chromosome by making use of Y-specific sequence-tagged sites (STSs). The sex-determining region Y and centromere were verified, and there were microdeletions on the long arm of the Y chromosome. The azoospermia factor (AZF) b region was partially deleted, and AZFa and AZFc were completely deleted. Two STS probes of sY143 and the Y chromosome RNA recognition motif in AZFb showed positive signals corresponding to Yq11.223. The karyotype of the patient was interpreted as 46,X,der(Y)del(Y)(q11.21q11.222)del(Y)(q11.23qter). Herein, we report a rare case of a boy presenting with gynecomastia and short stature with 46, X, +mar, which originated from the Y chromosome, which was identified to have Yq microdeletions.
Subject(s)
Adolescent , Humans , Male , Arm , Azoospermia , Centromere , Estradiol , Fluorescence , Follicle Stimulating Hormone , Foot , Genitalia , Gynecomastia , Hand , In Situ Hybridization , Karyotype , Metacarpal Bones , Metatarsal Bones , Overweight , Polymerase Chain Reaction , Reference Values , RNA , Sequence Tagged Sites , Testosterone , Toes , Y ChromosomeABSTRACT
OBJECTIVE: The aim of this study was to compare the efficacy of swim-up and density gradient centrifugation (DGC) for reducing the amount of sperm with fragmented DNA, sex chromosome aneuploidy, and abnormal chromatin structure. METHODS: Semen samples were obtained from 18 healthy male partners who attended infertility clinics for infertility investigations and were processed with swim-up and DGC. The percentages of sperm cells with fragmented DNA measured by the sperm chromatin dispersion test, normal sex chromosomes assessed by fluorescence in situ hybridization, and abnormal chromatin structure identified by toluidine blue staining were examined. RESULTS: The percentage of sperm cells with fragmented DNA was significantly lower in the swim-up fraction (9.7%, p=0.001) than in the unprocessed fraction (27.0%), but not in the DGC fraction (27.8%, p=0.098). The percentage of sperm cells with normal X or Y chromosomes was comparable in the three fractions. The percentage of sperm cells with abnormal chromatin structure significantly decreased after DGC (from 15.7% to 10.3%, p=0.002). The swim-up method also tended to reduce the percentage of sperm cells with abnormal chromatin structure, but the difference was not significant (from 15.7% to 11.6%, p=0.316). CONCLUSION: The swim-up method is superior for enriching genetically competent sperm.
Subject(s)
Humans , Male , Aneuploidy , Centrifugation, Density Gradient , Chromatin , DNA Fragmentation , DNA , Fluorescence , In Situ Hybridization , Infertility , Methods , Semen , Sex Chromosomes , Spermatozoa , Tolonium Chloride , Y ChromosomeABSTRACT
BACKGROUND: The nuclear architecture of meiotic prophase spermatocytes is based on higher-order patterns of spatial associations among chromosomal domains and consequently is prone to modification by chromosomal rearrangements. We have shown that nuclear architecture is modified in spermatocytes of Robertsonian (Rb) homozygotes of Mus domesticus. In this study we analyse the synaptic configuration of the quadrivalents formed in the meiotic pro- phase of spermatocytes of mice double heterozygotes for the dependent Rb chromosomes: Rbs 11.16 and 16.17. RESULTS: Electron microscope spreads of 60 pachytene spermatocytes from four animals of Mus domesticus 2n = 38 were studied and their respective quadrivalents analysed in detail. Normal synaptonemal complex was found between arms 16 of the Rb metacentric chromosomes, telocentrics 11 and 17 and homologous arms of the Rb metacentric chromosomes. About 43% of the quadrivalents formed a synaptonemal complex between the heterologous short arms of chromosomes 11 and 17. This synaptonemal complex is bound to the nuclear envelope through a fourth synapsed telomere, thus dragging the entire quadrivalent to the nuclear envelope. About 57% of quadrivalents showed unsynapsed single axes in the short arms of the telocentric chromosomes. About 90% of these unsynapsed quadrivalents also showed a telomere-to-telomere association between one of the single axes of the telocentric chromosome 11 or 17 and the X chromosome single axis, which was otherwise normally paired with the Y chromosome. Nucleolar material was associated with two bivalents and with the quadrivalent. CONCLUSIONS: The spermatocytes of heterozygotes for dependent Rb chromosomes formed a quadrivalent where four chromosomes are synapsed together and bound to the nuclear envelope through four telomeres. The nuclear configuration is determined by the fourth shortest telomere, which drags the centromere regions and heterochromatin of all the chromosomes towards the nuclear envelope, favouring the reiterated encounter and eventual rearrangement between the heterologous chromosomes. The unsynapsed regions of quadrivalents are frequently bound to the single axis of the X chromosome, possibly perturbing chromatin condensation and gene expression.
Subject(s)
Animals , Male , Mice , Spermatocytes/physiology , Spermatocytes/ultrastructure , X Chromosome/physiology , Y Chromosome/physiology , Synaptonemal Complex/physiology , Cell Nucleolus/physiology , Translocation, Genetic , X Chromosome/genetics , Y Chromosome/genetics , Synaptonemal Complex/genetics , Heterochromatin/physiology , Heterochromatin/genetics , Cell Nucleolus/genetics , Telomere/physiology , Telomere/genetics , Meiotic Prophase I/physiology , Meiotic Prophase I/genetics , HeterozygoteABSTRACT
To assess the prevalence of Y-chromosome sequences and gonadoblastoma in patients with Turner syndrome (TS) using molecular techniques. Data source: A literature search was performed in Pubmed, limiting the period of time to the years 20052014 and using the descriptors: TS and Y sequences (n=26), and TS and Y-chromosome material (n=27). The inclusion criteria were: articles directly related to the subject and published in English or Portuguese. Articles which did not meet these criteria and review articles were excluded. After applying these criteria, 14 papers were left. Data synthesis: The main results regarding the prevalence of Y-chromosome sequences in TS were: (1) about 60% of the studies were conducted by Brazilian researchers; (2) the prevalence varied from 4.6 to 60%; (3) the most frequently investigated genes were SRY, DYZ3 and TSPY; (4) seven studies used only polymerase chain reaction, while in the remaining seven it was associated with FISH. Nine of the 14 studies reported gonadectomy and gonadoblastoma. The highest prevalence of gonadoblastoma (33%) was found in two studies. In five out of the nine papers evaluated the prevalence of gonadoblastoma was 1025%; in two of them it was zero. Conclusions: According to these data, molecular analysis to detect Y-chromosome sequences in TS patients is indicated, regardless of their karyotype. In patients who test positive for these sequences, gonadoblastoma needs to be investigated.
Apresentar a prevalência de sequências do cromossomo Y por técnicas moleculares e de gonadoblastoma em pacientes com síndrome de Turner. Fontes de dados: Foi feita uma pesquisa bibliográfica no Pubmed, com limite de período entre 2005 e 2014, com os descritores Turner syndrome and Y sequences (n=26) e Turner syndrome and Y chromosome material (n=27). Os critérios de inclusão foram artigos que tivessem relação direta com o tema e publicados no idioma inglês ou português. Foram excluídos aqueles que não cumpriram esses critérios e eram do tipo revisão. Após aplicação desses critérios, 14 foram selecionados. Síntese dos dados: Os principais resultados quanto à prevalência de sequências do cromossomo Y em síndrome de Turner foram: 1 cerca de 60% dos estudos foram feitos por pesquisadores brasileiros; 2 a frequência variou de 4,6 a 60%; 3 os genes SRY, DYZ3 e TSPY foram os mais investigados; 4 a técnica de PCR foi empregada exclusivamente em sete estudos e nos sete restantes, associada à FISH. Nove dos 14 estudos apresentaram informações sobre gonadectomia e gonadoblastoma. Dois estudos relataram a maior prevalência para gonadoblastoma (33%). Cinco dos nove estudos referiram prevalência de 10 a 25% e em dois esse valor foi nulo. Conclusões: De acordo com os dados apresentados, é indicada a pesquisa molecular para sequências do cromossomo Y em pacientes com ST, independentemente do cariótipo. Naquelas com positividade para essas sequências, é necessária a investigação de gonadoblastoma.
Subject(s)
Humans , Y Chromosome , Gonadoblastoma , Prevalence , Polymerase Chain Reaction , Turner SyndromeABSTRACT
Mitochondrial DNA (mt DNA) and the non-recombining region of the Y chromosome are passed down, unaltered, from generation to generation, matrilineally and patrilineally, respectively. Therefore, the Y-chromosome DNA and mtDNA are known as lineage markers, and they play important roles in studies based on human migration and evolutionary history. Y-chromosome DNA is used in forensic analysis to identify individuals involved in cases of sexual assault. In this paper, we review the methods of statistical evaluation of lineage markers used in forensic identification. We also review the combined approach of autosomal and lineage marker evidence.
Subject(s)
DNA , DNA, Mitochondrial , Human Migration , Y ChromosomeABSTRACT
A 31-year-old woman, who was pregnant with twins, underwent chorionic villus sampling because of increased nuchal translucency in one of the fetuses. Cytogenetic analysis showed a normal karyotype in the fetus with increased nuchal translucency. However, the other fetus, with normal nuchal translucency, had a derivative X chromosome (der(X)). For further analysis, fluorescence in situ hybridization (FISH) and additional molecular studies including fragile X analysis were performed. FISH analysis confirmed that the Y chromosome was the origin of extra segment of the der(X). The X-chromosome breakpoint was determined to be at Xq27 by FMR1 CGG repeat analysis, and the Y-chromosome breakpoint was determined to be at Yq11.23 by the Y chromosome microdeletion study. To predict the fetal outcome, the X-inactivation pattern was examined, and it revealed non-random X inactivation of the der(X). To the best of our knowledge, the identification of an unbalanced Xq;Yq translocation at prenatal diagnosis has never been reported. This study was performed to identify precise breakpoints and the X-inactivation pattern as well as to provide the parents with appropriate genetic counseling.
Subject(s)
Adult , Female , Humans , Pregnancy , Chorionic Villi Sampling , Cytogenetic Analysis , Fetus , Fluorescence , Genetic Counseling , In Situ Hybridization , Karyotype , Nuchal Translucency Measurement , Parents , Prenatal Diagnosis , Twins , X Chromosome , X Chromosome Inactivation , Y ChromosomeABSTRACT
The Y-chromosome, as with other chromosomes in the cell, is subject to mutations. However, unlike autosomal genes, the Y chromosome does not undergo recombination, and therefore individuals from different geographical regions may have differing distribution patterns with respect to Y-chromosome mutations. More detailed knowledge and information regarding Y-chromosome mutations might therefore provide insights into phylogenetic history and personal identification. Here, we describe a case study involving genotype-phenotype discrepancy in an Indian male individual. We found that the mistyping in sex determination was caused by a deletion in the amelogenin Y (AMEL Y) gene. Furthermore, on examining the short tandem repeat (Y-STR) loci using the PowerPlex(R) Y23 System, we found four more deleted loci on Yp11.2 (DYS576, DYS481, DYS570, and DYS458) in this sample. We performed deletion mapping for this sample, and we propose that the microdeletion on the Yp11.2 locus occurred approximately in the 6.44 Mb to 9.75 Mb region. Previous studies have reported that the AMEL Y deletion is a common mutation in the Indian population. Taking into account regional differences, we also analyzed several area-specific Y-chromosome mutations.
Subject(s)
Humans , Male , Amelogenin , DNA , Microsatellite Repeats , Recombination, Genetic , Y ChromosomeABSTRACT
PURPOSE: Whether parental origin of the intact X chromosome and/or the presence of Y chromosome sequences (Yseq) play a role in three-year height response to growth hormone (GH) were investigated. METHODS: Paternal (Xp) or maternal (Xm) origin of X chromosome was assessed by microsatellite marker analysis and the presence of hidden Yseq was analyzed. The first-, second-, and third-year GH response was measured as a change in height z-score (Z_Ht) in Turner syndrome (TS) patients with 45,Xp (n=10), 45,Xm (n=15), and 45,X/46,X,+mar(Y) (Xm_Yseq) (n=8). RESULTS: The mean baseline Z_Ht did not differ according to Xp or Xm origin, however the mean baseline Z_Ht was higher in the Xm_Yseq group than in Xm group, after adjusting for bone age delay and midparental Z_Ht (P=0.04). There was no difference in the height response to GH between the 3 groups. The height response to GH decreased progressively each year (P<0.001), such that the third-year increase in Z_Ht was not significant. This third-year decrease in treatment response was unaffected by Xp, Xm, and Xm_Yseq groups. Increasing GH dosage from the second to third-year of treatment positively correlated with the increase in Z_Ht (P=0.017). CONCLUSION: There was no evidence of X-linked imprinted genes and/or Yseq affecting height response to 3 years of GH therapy. Increasing GH dosages may help attenuate the decrease in third-year GH response in TS patients with 45,X and/or 46,X/+mar(Y).
Subject(s)
Humans , Genomic Imprinting , Growth Hormone , Microsatellite Repeats , Parents , Turner Syndrome , X Chromosome , Y ChromosomeABSTRACT
As disgenesias gonadais parcial (DGP) e mista (DGM) caracterizam-se por ambiguidade genital e presença de gônada disgenética associada a testículo disgenético ou dois testículos disgenéticos. Na DGP o cariótipo é 46,XY; na DGM, há mosaico 45,X/46,XY ou suas variantes (mais de duas linhagens e (ou) anomalias estruturais do cromossomo Y). Esses mosaicos podem determinar, ainda, fenótipo feminino com síndrome de Turner (ST), distúrbio da diferenciação do sexo ovotesticular (DDS OT) e esterilidade em homens com genitais normais. Independentemente do fenótipo gonadal e genital, esses indivíduos apresentam outros sinais clínicos decorrentes da linhagem 45,X, como baixa estatura, dismorfismos, anomalias cardíacas e renais e diversas afecções adquiridas. Nos últimos anos surgiram evidências de ligação entre microdeleções do Y e o mosaicismo com linhagem 45,X. Há, ainda, indicações de que a instabilidade cromossômica trazida por essas deleções possa ser mais pronunciada nas gônadas. O objetivo deste trabalho foi investigar a presença de microdeleções do Y em indivíduos com DGP e naqueles com mosaico 45,X/46,XY ou suas variantes e diferentes fenótipos. A casuística constou de 15 indivíduos com DGP e 15 com mosaicismo, dos quais a maioria apresentava DGM (11 casos). Foram analisados 38 sequence tagged sites (STS) cobrindo a região específica masculina (MSY, male specific region) em Yp, centrômero e Yq por meio da técnica de reação em cadeia da polimerase (PCR) multiplex e individual. Todos os STS investigados nos indivíduos com DGP tiveram amplificação positiva, porém havia STS de Yq ausentes em seis indivíduos com mosaicismo e DGM, dos quais dois sem alterações estruturais de Y evidentes ao cariótipo. Essas deleções se localizavam em regiões contendo genes relacionados à espermatogênese (AZFb e AZFc - azoospermia factor)...
Partial and mixed gonadal dysgenesis (PGD and MGD) are characterized by genital ambiguity and the finding of either a streak gonad and a dysgenetic testis or two dysgenetic testes. In PGD there is a 46,XY karyotype, whereas in MGD there is a 45,X/46,XY mosaic or its variants (more than two lineages and/or structural abnormalities of the Y chromosome). These mosaics are also compatible with a female phenotype and Turner syndrome, ovotesticular disorder of sex development, and infertility in men with normal external genitalia. Regardless of the gonadal and genital phenotypes, these individuals present other clinical features associated with the 45,X cell line, including short stature, dysmorphisms, cardiovascular and renal anomalies and various acquired diseases. During the last few years, evidences of a link between Y microdeletions and 45,X mosaicism have been reported. There are also indications that the instability caused by such deletions might be more significant in germ cells. The aim of this work was to investigate the presence of Y chromosome microdeletions in individuals with PGD and in those with 45,X/46,XY mosaicism or its variants and variable phenotypes. Our sample comprised 15 individuals with PGD and 15 with mosaicism, most of them with a MGD phenotype (n=11). Thirty-eight sequence tagged sites (STS) spanning the male specific region (MSY) on the Y chromosome (Yp, centromere and Yq) where analyzed by multiplex PCR and some individual reactions. All STS showed positive amplifications in the PGD group. Conversely, in the group with mosaicism, six individuals with MGD had been identified with Yq microdeletions, two of them did not have structural abnormalities of the Y chromosome recognized by routine cytogenetic analysis. The deleted STSs were located within AZFb and AZFc (Azoospermia Factor) regions, which harbor several genes responsible for spermatogenesis...
Subject(s)
Humans , Male , Chromosome Deletion , Y Chromosome , MosaicismABSTRACT
In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae). The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome) or both sex chromosomes (X and Y chromosomes). This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes) and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.