SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility.

Unexplained infertility affects 2%-3% of reproductive-aged couples. One approach to identifying genes involved in infertility is to study subjects with this clinical phenotype and a de novo balanced chromosomal aberration (BCA). While BCAs may reduce fertility by production of unbalanced gametes, a chromosomal rearrangement may also disrupt or dysregulate genes important in fertility. One such subject, DGAP230, has severe oligozoospermia and 46,XY,t(20;22)(q13.3;q11.2). We identified exclusive overexpression of SYCP2 from the der(20) allele that is hypothesized to result from enhancer adoption. Modeling the dysregulation in budding yeast resulted in disrupted structural integrity of the synaptonemal complex, a common cause of defective spermatogenesis in mammals. Exome sequencing of infertile males revealed three heterozygous SYCP2 frameshift variants in additional subjects with cryptozoospermia and azoospermia. In sum, this investigation illustrates the power of precision cytogenetics for annotation of the infertile genome, suggests that these mechanisms should be considered as an alternative etiology to that of segregation of unbalanced gametes in infertile men harboring a BCA, and provides evidence of SYCP2-mediated male infertility in humans.

Comprehension Profile of Patient Education Materials in Endocrine Care.

Introduction: The internet is an ever-evolving resource to improve healthcare literacy among patients. The nature of the internet can make it difficult to condense educational materials in a manner applicable to a worldwide patient audience. Within the realm of endocrinology, there is lack of a comprehensive analysis regarding these pathologies in addition to education materials related to their medical work-up or management. The aim of this study was to assess contemporary online patient education material in endocrinology and management of care. Methods: Analysis of the readability of 1,500 unique online education materials was performed utilizing seven readability measures: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index Readability Formula (FOG), Simple Measure of Gobbledygook Index (SMOG), Coleman-Liau Index (CLI), automated readability index (ARI), and Linsear Write Formula (LWF). Results: The average grade level readability scores from six measures (e.g., FKGL, FOG, SMOG, CLI, ARI, LWF) was more than or equal to 11 which corresponds to a reading level at or above the 11th grade. The average FRE between adrenal, diabetes, and thyroid-related education m aterial ranged between "fairly difficult" to "very difficult". Conclusions: The readability of contemporary online endocrine education material did not meet current readability recommendations for appropriate comprehension of the general audience.

Perceived Depression, Anxiety, and Stress Outcomes Among Students of Early Entrance College Programs.

Introduction Mental health disorders affect adolescents and children and have resulted in many academic institutions now recognizing and taking steps to reduce the pressure they place on students. Early Entrance to College Programs (EECP) is a small subset of academic institutions focused on providing an accelerated higher education path, and these students are held to high academic standards. It is important to research the effects of these programs on the students' mental health, as younger children are extremely susceptible to mental disorders that may last into adulthood.  Methods This study analyzed a three-part survey given to alumni of various EECPs. The survey is a combination of Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and yes/no questions regarding the participants' demographics. A longitudinal study was also conducted on current students in EECPs. These students were given a survey consisting of the 21-item Depression, Anxiety, and Stress Scale (DASS-21) questionnaire, which was completed two times throughout the academic year, three months later. Results The results displayed that there was a significant impact of academic rigor on the mental health of these students. In both the one-time and longitudinal studies, a majority of participants recorded having higher levels of anxiety and depression than before they were in the program. Conclusions The association between mental health and academic rigor is similar to what is seen among both high school and college cohort students with a greater emphasis on the social environment as a modulating factor.

Computational Prediction of Position Effects of Human Chromosome Rearrangements.

Balanced and apparently balanced chromosome abnormalities (BCAs) have long been known to generate disease through position effects, either by altering local networks of gene regulation or positioning genes in architecturally different chromosome domains. Despite these observations, identification of distally affected genes by BCAs is oftentimes neglected, especially when predicted gene disruptions are found elsewhere in the genome. In this unit, we provide detailed instructions on how to run a computational pipeline that identifies relevant candidates of non-coding BCA position effects. This methodology facilitates quick identification of genes potentially involved in disease by non-coding BCAs and other types of rearrangements, and expands on the importance of considering the long-range consequences of genomic lesions.

Effects of Antioxidants in Human Cancers: Differential Effects on Non-Coding Intronic RNA Expression.

The notion that dietary antioxidants can help fight cancer is popular. However, the mechanism(s) behind the effect of antioxidants in cancer is still unclear. Previous studies indicate that supplements can influence gene expression; however, all of these studies were focused on the coding/exonic gene expression. Studies are now emerging to highlight critical functional roles for RNAs expressed from the non-coding regions. This project was designed to study the effect of antioxidant supplements on non-coding intronic RNA expression in human cancers. Vitamin E, N-Acetyl cysteine (NAC) and Sulforaphane are commonly used supplements to prevent diseases including cancers. We studied the effect of these antioxidant supplements on the non-coding intronic RNA expression using publicly available datasets from a mouse model for lung cancer and prostate cancer cell lines. Although high throughput polyA-enriched RNA-Seq data characterize spliced coding mRNA regions, recent studies reveal the expression of reads from the non-coding intronic regions. Our analyses indicate that cancer cells have higher expression of introns compared to that of normal cells and that treatment with antioxidant supplements reduces the increased expression of introns of several genes. However, we did find high expression of introns of multiple genes including many oncogenes in the supplement treated groups compared to that of the control; this effect was distinct depending on the cell type and the supplement studied. Using RT-PCRs, we validated the expression of introns of two oncogenes, DLK1 and LRG1, known to be key players in lung cancer progression, and demonstrate changed intronic expression with supplement treatment in cancer cells. With regard to the antioxidant system, supplements did not change the intronic RNAs for endogenous antioxidant enzymes except for a significant decrease in the expression of superoxide dismutase (SOD) intronic RNA. Concurrently, we also found that a prolonged (48 h) exposure to Vitamin C, Vitamin E and Green tea extract reduced the enzymatic activity of SOD in lung cancer cells. The results from this study reveal that the antioxidant supplements have a significant effect on the intronic RNA expression of many genes including cancer genes that are not directly linked to the body's antioxidant system. It is important to study this novel effect of antioxidant supplements in detail as it may have a significant role in disease progression.