Cellular and Molecular Genetic Analysis of 1980 Male Infertility Patients

Background The aims of this study were to investigate the distribution of chromosome karyotype abnormality and azoospermia factor (AZF) microdeletion on Y chromosome in male infertility patients and its effect on infertility. Further, the study aimed to guide fertility in patients. Methods A total of 1980 azoospermic and oligoospermic male infertility patients were selected from the male outpatient department of our hospital from January 2016 to December 2019. Peripheral blood was collected from the patients for karyotype analysis. Further, AZF microdeletion analysis on Y chromosome was performed by capillary electrophoresis. Results Among the patients of male infertility, 178 had chromosomal abnormality (8.99%, 178/1980). Among them, 98 had an abnormal chromosome number. Among the 98 patients, 47, XXY was the most common (80 cases), accounting for 44.99 % (80/178) of abnormal karyotypes. There were 211 cases of AZF microdeletion on Y chromosome, with a total deletion rate of 10.66% (211/1980). The most common type was AZFb/c deletion (sY1192 140 cases), accounting for 66.3 % (140/211). Conclusion Karyotype abnormality and AZF gene microdeletion are important causes of male infertility. Men with Yqh-, del(Y) (q11) have a higher risk of AZF microdeletion. Infertility patients should routinely undergo cell and molecular genetic tests to guide patient fertility.

A probabilistic model for indel evolution: differentiating insertions from deletions

Insertions and deletions (indels) are common molecular evolutionary events. However, probabilistic models for indel evolution are under-developed due to their computational complexity. Here we introduce several improvements to indel modeling: (1) While previous models for indel evolution assumed that the rates and length distributions of insertions and deletions are equal, here we propose a richer model that explicitly distinguishes between the two; (2) We introduce numerous summary statistics that allow Approximate Bayesian Computation (ABC) based parameter estimation; (3) We develop a method to correct for biases introduced by alignment programs, when inferring indel parameters from empirical datasets; (4) Using a model-selection scheme we test whether the richer model better fits biological data compared to the simpler model. Our analyses suggest that both our inference scheme and the model-selection procedure achieve high accuracy on simulated data. We further demonstrate that our proposed richer model better fits a large number of empirical datasets and that, for the majority of these datasets, the deletion rate is higher than the insertion rate.

Mitochondrial DNA 4977 bp Deletion in Peripheral Blood Is Associated With Polycystic Ovary Syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder worldwide. We aimed to examine the associations of two mitochondrial DNA (mtDNA) biomarkers in the peripheral blood, mtDNA copy number (CN), and mtDNA4977 deletion rate (DR), with PCOS in a clinical setting.MethodsWe performed a study involving 263 women with PCOS and 326 age-matched controls between June 2015 and June 2019. The mtDNA CN and mtDNA4977 DR were measured using multiplex probe-based qPCR. The associations of the mtDNA CN and mtDNA4977 DR with the risk of PCOS were estimated using logistic regression.ResultsAnalysis of the associations between mtDNA biomarkers and PCOS indicate that the mtDNA CN (P = 0.003) and mtDNA4977 DR (P < 0.001) in PCOS patients were significantly higher than those in the controls. After adjusting for the body mass index, luteinizing hormone/follicle-stimulating hormone ratio, and testosterone level, only higher mtDNA4977 DR was associated with PCOS (odds ratio 1.053, 95% confidence interval 1.024 to 1.083; P < 0.001). The linear dose-response trends of the mtDNA4977 DR were also supported by the quartile analysis.ConclusionMultivariable models suggest that mtDNA4977 DR levels are strongly associated with PCOS and represent an independent risk factor for PCOS. Further investigation of the utility of mtDNA as a biomarker for PCOS is warranted.

A probabilistic model for indel evolution: differentiating insertions from deletions

Insertions and deletions (indels) are common molecular evolutionary events. However, probabilistic models for indel evolution are under-developed due to their computational complexity. Here we introduce several improvements to indel modeling: (1) while previous models for indel evolution assumed that the rates and length distributions of insertions and deletions are equal, here, we propose a richer model that explicitly distinguishes between the two; (2) We introduce numerous summary statistics that allow Approximate Bayesian Computation (ABC) based parameter estimation; (3) We develop a neural-network model-selection scheme to test whether the richer model better fits biological data compared to the simpler model. Our analyses suggest that both our inference scheme and the model-selection procedure achieve high accuracy on simulated data. We further demonstrate that our proposed indel model better fits a large number of empirical datasets and that, for the majority of these datasets, the deletion rate is higher than the insertion rate. Finally, we demonstrate that indel rates are negatively correlated to the effective population size across various phylogenomic clades.

Analysis of the copy number of the BRCA1, NF-κB1 and PARP1 genes in patients with luminal B breast cancer

Целью работы явилась оценка связи хромосомных аберраций генов BRCA1, NF-κB1, PARP1 в опухолевой ткани молочной железы с эффектом химиотерапии и прогнозом заболевания. В исследование включены 85 больных люминальным В раком молочной железы IIA-IIIB стадии, с морфологически верифицированным диагнозом, в возрасте 25-68 лет (47,8±1,1). Было установлено, что наибольшая частота делеций наблюдается в гене BRCA1 (36%, 30 случаев из 85). Частота амплификаций PARP1 в исследуемой группе больных РМЖ достигает 62% (53 случая из 85). Наименьшее число хромосомных аберраций наблюдается в гене NF-κB1, всего у 22 больных наблюдаются делеции и амплификации данного гена (26%). Показано, что делеция гена BRCA1 сопряжена с хорошим ответом на неоадъювантную химиотерапию вне зависимости от наличия хромосомных аберраций других генов. При этом амплификация PARP1 связана с плохим прогнозом заболевания. The aim of the work was to assess the relationship of chromosomal aberrations of the BRCA1, NF-κB1, PARP1 genes in breast tumor tissue with the effect of chemotherapy and prognosis of the disease. The study included 85 patients with luminal stage IIA-IIIB breast cancer, with a morphologically verified diagnosis, aged 25-68 years (47.8±1.1). As a result of the study, the CNA frequency of the studied genes was estimated. It was found that the highest deletion rate is observed in the BRCA1 gene (36%, 30 cases out of 85). The frequency of amplification of PARP1 in the studied group of breast cancer patients reaches 62% (53 cases out of 85). The smallest number of chromosomal aberrations is observed in the NF-κB1 gene; in only 22 patients, deletions and amplifications of this gene are observed (26%). it was found that the deletion of the BRCA1 gene is associated with a good response to neoadjuvant chemotherapy, regardless of the presence of chromosomal aberrations of other genes. Moreover, amplification of PARP1 is associated with a poor prognosis of the disease.

Attitudes and exposure as predictors of -t/d deletion among local and expatriate children in Singapore

Although orientation towards local norms is increasing in Singapore, Singapore English (SgE) is still perceived by some as a nonnative variety. Variation in attitudes towards SgE may shape acquisition of SgE features by both Singaporean and expatriate children, who increasingly attend government schools. The present study investigates how the -t/d deletion patterns of 60 children reflect their attitudes and school setting. Significant correlations are observed between deletion rate, attitude towards SgE, and accent self-perception among Singaporean children, highlighting that this variety is undergoing endonormative stabilization. However, while some expatriates in local schools delete more than peers in international schools, expatriate children generally do not acquire local -t/d deletion rates or constraints, regardless of familiarity with SgE or attitudes towards the variety. This gap between locals and expatriates reflects the persistence of ideologies that delegitimize SgE, as well as the growing prominence of SgE as a marker of local identity.