Frequency of Common Copy-Number Variations at 15q11.2q13 in Sperm of Healthy Men

2019 ◽  
Vol 159 (2) ◽  
pp. 66-73 ◽  
Author(s):  
Takahiro Kinoshita ◽  
Masashi Mikami ◽  
Tadayuki Ayabe ◽  
Keiko Matsubara ◽  
Hiromi Ono ◽  
...  
Keyword(s):  
Copy Number ◽  
Alcohol Intake ◽  
Negative Binomial ◽  
Smoking Status ◽  
Clinical Information ◽  
Estimating Equation ◽  
Copy Number Variations ◽  
Genomic Region ◽  
Healthy Men ◽  
Significant Difference

The genomic region at 15q11.2q13 represents a hotspot for copy-number variations (CNVs) due to nonallelic homologous recombination. Previous studies have suggested that the development of 15q11.2q13 deletions in sperm may be affected by seasonal factors because patients with Prader-Willi syndrome resulting from 15q11.2q13 deletions on paternally derived chromosomes showed autumn-dominant birth seasonality. The present study aimed to determine the frequency of 15q11.2q13 CNVs in sperm of healthy men and clarify the effects of various environmental factors, i.e., age, smoking status, alcohol intake, and season, on the frequency. Thirty volunteers were asked to provide semen samples and clinical information once in each season of a year. The rates of 15q11.2q13 CNVs were examined using 2-color FISH. The results were statistically analyzed using a generalized estimating equation with negative binomial distribution and a log link function. Consequently, informative data were obtained from 83 samples of 26 individuals. The rates of deletions and duplications ranged from 0.04 to 0.48% and from 0.08 to 0.30%, respectively. The rates were not correlated with the age, smoking status, or alcohol intake. Sperm produced in winter showed 1.2 to 1.4-fold high rates for both deletions and duplications as compared with sperm produced in the other seasons; however, there was no significant difference. These results demonstrate high and variable CNV rates at 15q11.2q13 in sperm of healthy men. These CNVs appear to occur independent of the age, smoking status, or alcohol intake, while the effect of season remains inconclusive. Our results merit further validation.

scholarly journals Evaluation of Chromosomal Abnormalities and Copy Number Variations in Fetuses with Ultrasonic Soft Markers

2020 ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Liangpu Xu ◽  
hailong huang
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Copy Number Variations ◽  
Clinical Value ◽  
Obstetrical Outcomes ◽  
Genetic Abnormalities ◽  
Significant Difference ◽  
Snp Array Analysis ◽  
Soft Marker

Abstract Background: Some ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers.Methods: Among 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis. Results: Among 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups.Conclusions: Genetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect obstetrical outcomes.

scholarly journals Frequency of the STRC-CATSPER2 deletion in STRC-associated hearing loss patients

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shin-ya Nishio ◽  
Shin-ichi Usami
Keyword(s):  
Hearing Loss ◽  
Male Infertility ◽  
Genetic Counselling ◽  
Copy Number ◽  
Read Depth ◽  
Copy Number Variations ◽  
Genomic Region ◽  
High Prevalence ◽  
Homozygous Deletions ◽  
Next Generation Sequencing Ngs

AbstractThe STRC gene, located on chromosome 15q15.3, is one of the genetic causes of autosomal recessive mild-to-moderate sensorineural hearing loss. One of the unique characteristics of STRC-associated hearing loss is the high prevalence of long deletions or copy number variations observed on chromosome 15q15.3. Further, the deletion of chromosome 15q15.3 from STRC to CATSPER2 is also known to be a genetic cause of deafness infertility syndrome (DIS), which is associated with not only hearing loss but also male infertility, as CATSPER2 plays crucial roles in sperm motility. Thus, information regarding the deletion range for each patient is important to the provision of appropriate genetic counselling for hearing loss and male infertility. In the present study, we performed next-generation sequencing (NGS) analysis for 9956 Japanese hearing loss patients and analyzed copy number variations in the STRC gene based on NGS read depth data. In addition, we performed Multiplex Ligation-dependent Probe Amplification analysis to determine the deletion range including the PPIP5K1, CKMT1B, STRC and CATSPER2 genomic region to estimate the prevalence of the STRC-CATSPER deletion, which is causative for DIS among the STRC-associated hearing loss patients. As a result, we identified 276 cases with STRC-associated hearing loss. The prevalence of STRC-associated hearing loss in Japanese hearing loss patients was 2.77% (276/9956). In addition, 77.1% of cases with STRC homozygous deletions carried a two copy loss of the entire CKMT1B-STRC-CATSPER2 gene region. This information will be useful for the provision of more appropriate genetic counselling regarding hearing loss and male infertility for the patients with a STRC deletion.

scholarly journals Comprehensive Genomic Analysis Reveals the Prognostic Role of LRRK2 Copy-Number Variations in Human Malignancies

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 846
Author(s):  
Gianluca Lopez ◽  
Giulia Lazzeri ◽  
Alessandra Rappa ◽  
Giuseppe Isimbaldi ◽  
Fulvia Milena Cribiù ◽  
...  
Keyword(s):  
Copy Number ◽  
Prognostic Significance ◽  
Point Mutations ◽  
Genomic Analysis ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Cancer Development ◽  
Future Research ◽  
Gene Deletions ◽  
Significant Difference

Genetic alterations of leucine-rich repeat kinase 2 (LRRK2), one of the most important contributors to familial Parkinson’s disease (PD), have been hypothesized to play a role in cancer development due to demographical and preclinical data. Here, we sought to define the prevalence and prognostic significance of LRRK2 somatic mutations across all types of human malignancies by querying the publicly available online genomic database cBioPortal. Ninety-six different studies with 14,041 cases were included in the analysis, and 761/14,041 (5.4%) showed genetic alterations in LRRK2. Among these, 585 (76.9%) were point mutations, indels or fusions, 168 (22.1%) were copy number variations (CNVs), and 8 (1.0%) showed both types of alterations. One case showed the somatic mutation R1441C. A significant difference in terms of overall survival (OS) was noted between cases harboring somatic LRRK2 whole deletions, amplifications, and CNV-unaltered cases (median OS: 20.09, 57.40, and 106.57 months, respectively; p = 0.0008). These results suggest that both LRRK2 amplifications and whole gene deletions could play a role in cancer development, paving the way for future research in terms of potential treatment with LRRK2 small molecule inhibitors for LRRK2-amplified cases.

Influence of Rheumatoid Arthritis on Employment, Function, and Productivity in a Nationally Representative Sample in the United States

2010 ◽  
Vol 37 (3) ◽  
pp. 544-549 ◽  
Author(s):  
PATRICK W. SULLIVAN ◽  
VAHRAM GHUSHCHYAN ◽  
XING-YUE HUANG ◽  
DENISE R. GLOBE
Keyword(s):  
Rheumatoid Arthritis ◽  
Negative Binomial ◽  
Medical Expenditure Panel Survey ◽  
Smoking Status ◽  
International Classification Of Diseases ◽  
The United States ◽  
Medical Expenditure ◽  
Significant Difference ◽  
Inability To Work ◽  
Nationally Representative

Objective.The Medical Expenditure Panel Survey (MEPS) was used to estimate the national influence of rheumatoid arthritis (RA) on employment, limitations in work or housework, inability to work or do housework, missed work days, days spent sick in bed, and annual wages.Methods.MEPS is a nationally representative survey of the US population. Multiple logistic, negative binomial, and Heckman selection regression methods were used, controlling for age, sex, race, ethnicity, smoking status, income, education, and chronic comorbidity. RA was identified using International Classification of Diseases-9 code 714.Results.In unadjusted descriptive statistics, individuals with RA were older, had more chronic conditions, missed more work days, spent more days sick in bed, had lower employment rates, had higher rates of limitations and inability to work, and received disability benefits at higher rates. After adjustment, multiple regression analyses showed individuals with RA were 53% less likely to be employed [OR 0.47, 95% CI 0.34–0.65], 3.3 times more likely to have limitations in work or housework (95% CI 2.35–4.64), 2.3 times more likely to be unable to work or do housework (95% CI 1.55–3.53), and spent 3.6 times as many days sick in bed as those without RA (95% CI 2.32–5.53). RA was associated with an expected loss of $8957 in annual earnings (95% CI $1881–$15,937). There was no statistically significant difference in missed work days or the level of wages.Conclusion.In the most recent available national data for adults, RA was associated with reductions in employment, productivity, and function.

scholarly journals Penetrance of WT1 and WT2 Gene Mutation and Loss of Heterozygosity in Wilms tumors in Indian Population

2020 ◽  
Vol 5 (3) ◽  
Keyword(s):  
Gene Mutation ◽  
Loss Of Heterozygosity ◽  
Copy Number ◽  
Wilms Tumor ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Dna Copy Number ◽  
Pediatric Age Group ◽  
Significant Difference ◽  
Number Variation

Wilms tumor is a nephroblastoma of pediatric age group and heterogeneous in nature. WT1 and WT2 gene mutations are involved in onset of tumorigenesis in syndromic and non syndromic cases of Wilms tumor. Present study has been designed with aim to evaluate the frequency of WT1 and WT2 gene mutation, loss of heterozygosity (LOH) and DNA copy number variation (CNV) in clinically diagnosed cases of Wilms tumor using RT-PCR based analysis. Findings reveals that there was vast difference in the mutation frequency between WT1 (7.5%) and WT2 (17.5) gene, and statistical analysis shows significant difference (p < 0.05) in WT2 mutation and calculated value of C.I. varies between 0.886-1.990 at 95% with odd ratio (7.52). Interestingly, the frequency of LOH (loss of heterozygosity and DNA copy number variations (CNVs) shows significant difference (p < 0.01), suggesting increase of genetic susceptibility and penetrance of gene in proband of the family tumor resulting increase of risk factor after using three different microsatellite DNA markers (DS11S935, DS11S904 and DS11S1363). Genetic heterogenecity were also observed by calculating Tm values, between cases and controls (GAPDH), and C.I. varies between 0.292 - 2.270 at 95% with O.R = 0.54 in D11S1363 and maximum value of C.I. was 1.165-2.165 at 95% with O.R = 0.50 in D11S1905 and the p = 0.194 & p = 0.522 respectively, between cases and controls..

scholarly journals Combined Analysis of SNP Array Data Identifies Novel CNV Candidates and Pathways in Ependymoma and Mesothelioma

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Gabriel Wajnberg ◽  
Benilton S. Carvalho ◽  
Carlos G. Ferreira ◽  
Fabio Passetti
Keyword(s):  
Open Source ◽  
Open Source Software ◽  
Copy Number ◽  
Chemotherapy Resistance ◽  
Snp Array ◽  
Copy Number Variations ◽  
Genomic Region ◽  
Structural Genomic ◽  
Innovative Strategy ◽  
Novel Strategy

Copy number variation is a class of structural genomic modifications that includes the gain and loss of a specific genomic region, which may include an entire gene. Many studies have used low-resolution techniques to identify regions that are frequently lost or amplified in cancer. Usually, researchers choose to use proprietary or non-open-source software to detect these regions because the graphical interface tends to be easier to use. In this study, we combined two different open-source packages into an innovative strategy to identify novel copy number variations and pathways associated with cancer. We used a mesothelioma and ependymoma published datasets to assess our tool. We detected previously described and novel copy number variations that are associated with cancer chemotherapy resistance. We also identified altered pathways associated with these diseases, like cell adhesion in patients with mesothelioma and negative regulation of glutamatergic synaptic transmission in ependymoma patients. In conclusion, we present a novel strategy using open-source software to identify copy number variations and altered pathways associated with cancer.

scholarly journals Evaluation of chromosomal abnormalities and copy number variations in fetuses with ultrasonic soft markers

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Xuemei Chen ◽  
Meimei Fu ◽  
Nan Guo ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Copy Number Variations ◽  
Clinical Value ◽  
Single Nucleotide ◽  
Genetic Abnormalities ◽  
Significant Difference ◽  
Snp Array Analysis ◽  
Soft Marker

Abstract Background Some ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers. Methods Among 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis. Results Among 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups. Conclusions Genetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect pregnancy outcomes.

scholarly journals Analysis of XX SRY-Negative Sex Reversal Dogs

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1667 ◽  
Author(s):  
Sara Albarella ◽  
Lisa De Lorenzi ◽  
Elena Rossi ◽  
Francesco Prisco ◽  
Marita Georgia Riccardi ◽  
...  
Keyword(s):  
Copy Number ◽  
Promoter Region ◽  
Molecular Genetic ◽  
Disorders Of Sex Development ◽  
Sex Reversal ◽  
Copy Number Variations ◽  
Genomic Region ◽  
Chromosome 9 ◽  
Economic Losses ◽  
Sex Development

Impaired fertility associated with disorders of sex development (DSDs) due to genetic causes in dogs are more and more frequently reported. Affected dogs are usually of specific breeds thus representing a cause of economic losses for breeders. The aim of this research is to report the clinical, cytogenetic and molecular genetic findings of four XX SRY-negative DSD dog cases. All the subjects showed a female aspect and the presence of an enlarged clitoris with a penis bone. Morphopathological analyses performed in three of the four cases showed the presence of testes in two cases and ovotestis in another. Conventional and R-banded cytogenetic techniques were applied showing that no chromosome abnormalities were involved in these DSDs. CGH arrays show the presence of 11 copy number variations (CNVs), one of which is a duplication of 458 Kb comprising the genomic region between base 17,503,928 and base 17,962,221 of chromosome 9 (CanFam3 genome assembly). This CNV, confirmed also by qPCR, includes the promoter region of SOX9 gene and could explain the observed phenotype.

scholarly journals A Retrospective Study of Noninvasive Prenatal Testing for Chromosome Aneuploidies and Sub-Chromosomal Copy Number Variations in 24359 Single Pregnancies

2020 ◽  
Author(s):  
Yuefang Liu ◽  
Longfei Cheng ◽  
Yuan Peng ◽  
Zhe Liang ◽  
Pan Qiong
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number ◽  
False Negative ◽  
Prenatal Testing ◽  
Clinical Information ◽  
Copy Number Variations ◽  
Negative Case ◽  
Chromosomal Copy Number ◽  
Chromosomal Copy

Abstract Background: With the development of whole-genome sequencing, small sub-chromosomal deletions and duplications could be found by non-invasive prenatal testing(NIPT). This study aimed to review the efficiency of NIPT as a screening test for aneuploidies and sub-chromosomal copy number variations (CNVs) in 24359 single pregnancies.Methods: A total of 24359 single pregnancies with different clinical indications were retrospectively analyzed. The positive predictive value （PPV）of chromosome aneuploidies and subchromosomal CNVs were analyzed. Pathogenicity of abnormal NIPT results were assessed according to American College of Medical Genetics and Genomics(ACMG). Results: A total of 442 pregnancies (442/24359,1.9%) were with abnormal NIPT results. PPV for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), and sex chromosome aneuploidies (SCAs) was 84.8%, 54.2%, 11.1% an 40.5% respectively. The PPV for sub-chromosomal CNVs was 59.0% (46/78). The PPV for CNVs ≤5 Mb was 68.9% (31/45), for CNVs within 5-10 Mb was 83.3%(5/6) and for CNVs ≥10 Mb was 37.1% (10/27) respectively. The clinical information, prenatal diagnosis results and follow-up results of 46 true positive cases, 6 cases with sub-chromosomal CNVs inconsistent with NIPT and 1 false negative case were also described in detail.Conclusions: Our data have potential significance in demonstrating the significance of NIPT not only for common whole chromosome aneuploidies but also for sub-chromosomal CNVs. Besides, the clinical information, prenatal diagnosis results and follow-up results of 52 cases with sub-chromosomal CNVs and 1 false negative case would provide important guidance for genetic counseling.

scholarly journals Screening for Copy Number Variations of the 15q13.3 Hotspot in CHRNA7 Gene and Expression in Patients with Migraines

2021 ◽  
Vol 43 (2) ◽  
pp. 1090-1113
Author(s):  
Mehmet Fatih Özaltun ◽  
Sırma Geyik ◽  
Şenay Görücü Yılmaz
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Cholinergic Receptor ◽  
Copy Number Variations ◽  
Healthy Controls ◽  
Standard Curve ◽  
Copy Numbers ◽  
Significant Difference ◽  
Alpha 7

Background: a migraine is a neurological disease. Copy number variation (CNV) is a phenomenon in which parts of the genome are repeated. We investigated the effects of the CNV and gene expression at the location 15q13.3 in the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, which we believe to be effective in the migraine clinic. Methods: we evaluated changes in CHRNA7 gene expression levels and CNV of 15q13.3 in patients with migraine (n = 102, with aura, n = 43; without aura, n = 59) according to healthy controls (n = 120) by q-PCR. The data obtained were analyzed against the reference telomerase reverse transcriptase (TERT) gene with the double copy number by standard curve analysis. Copy numbers were graded as a normal copy (2), gain (2>), and loss (<2). Results: we analyzed using the 2−ΔΔCT calculation method. The CHRNA7 gene was significantly downregulated in patients (p < 0.05). The analysis of CNV in the CHRNA7 gene was statistically significant in the patient group, according to healthy controls (p < 0.05). A decreased copy number indicates a dosage loss. However, no significant difference was observed among gain, normal, and loss copy numbers and expression values in patients (p > 0.05). The change in CNV was not associated with the downregulation of the CHRNA7 gene. Conclusion: Downregulation of the CHRNA7 gene may contribute to the formation of migraine by inactivation of the alpha-7 nicotinic receptor (α7nAChR). The association of CNV gains and losses with migraines will lead to better understanding of the molecular mechanisms and pathogenesis, to better define the disease, to be used as a treatment target.

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