Medical Genetics Commons^™

Differential Strain-Dependent Ovarian And Metabolic Responses In A Mouse Model Of Pcos, April K. Binder, Danielle L. Peecher, Amanda J. Qvigstad, Silvia D. Gutierrez, Jennifer Magaña, David B. Banks, Kenneth S. Korach

Biology Faculty Scholarship

Several mouse models have been developed to study polycystic ovarian syndrome (PCOS), a leading cause of infertility in women. Treatment of mice with dihydrotestosterone (DHT) for 90-days causes ovarian and metabolic phenotypes similar to women with PCOS. We used this 90-day DHT treatment paradigm to investigate the variable incidence and heterogeneity in two inbred mouse strains, NOD/ShiLtJ and 129S1/SvlmJ. NOD mice naturally develop type 1 diabetes, and recent meta-analysis found increased androgen excess and PCOS in women with type 1 diabetes. 129S1 mice are commonly used in genetic manipulations. Both NOD and 129S1 DHT treated mice had early vaginal opening, …

Differential Transcriptional Alterations In Detoxification Genes In Parkinson’S Disease In Egypt, Nourhan Shebl

Theses and Dissertations

PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmental profiles, the Egyptian population is one of the mostunderrepresented population in terms of PD research. In this study, we investigated PD through various perspectives tohighlight the complexity of the disease in Egypt, taking into consideration the diversity of the Egyptian population. We recruited PD patients and reference controls from 4 governorates: Cairo, Giza, Alexandria, and …

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

Advancement In Human Face Prediction Using Dna, Aamer Alshehhi, Aliya Almarzooqi, Khadija Alhammadi, Naoufel Werghi, Guan Kwang Tay, Habiba Alsafar

Research outputs 2022 to 2026

The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly, this technology can be vital in forensic cases involving human identification from biological traces or human remains, especially when reference samples are not available in the deoxyribose nucleic acid (DNA) database. This review summarizes the currently used methods for predicting human phenotypes such as age, ancestry, pigmentation, and facial features based on genetic variations. To identify the facial features affected by DNA, various two-dimensional (2D)- and three-dimensional (3D)-scanning techniques and analysis tools are reviewed. A comparison between the scanning …

Molecular Subtyping And Survival Analysis Of Osteosarcoma Reveals Prognostic Biomarkers And Key Canonical Pathways, Siddesh Southekal, Sushil Kumar Shakyawar, Prachi Bajpai, Amr Elkholy, Upender Manne, Nitish Kumar Mishra, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. …

A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell A. Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan

Journal Articles: Genetics, Cell Biology & Anatomy

Porous alginate (Alg) hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden Alg hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of Alg and caseinate (Cas), are cross-linked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the Cas phase from the ion-cross-linked Alg hydrogel. Those …

Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz

Theses and Dissertations

The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the Kras^G12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Detecting Overlapping Gene Regions Using The U-Net Attention Mechanism, Samuel Lemma

All Graduate Theses, Dissertations, and Other Capstone Projects

The current issue of locating, diagnosing, and treating cancer and other diseases linked to specific target genes necessitates the creation of a reliable system for precisely identifying target genes that are initially extracted from a human chromosome. Current methodologies often suffer from overlapping gene regions in the target gene that occurs during the analysis process, which can have a substantial impact on the accuracy of the results. Our recommended approach, which was the appropriate model to apply for this particular problem, is set to enhance the analytical process by utilizing neural networks' U-Net with an attention mechanism. We were able …

Case Report: Sex-Specific Characteristics Of Epilepsy Phenotypes Associated With Xp22.31 Deletion: A Case Report And Review, Yi Wu, Dan Wu, Yulong Lan, Shaocong Lan, Duo Li, Zexin Zheng, Hongwu Wang, Lian Ma

Research outputs 2022 to 2026

Deletion in the Xp22.31 region is increasingly suggested to be involved in the etiology of epilepsy. Little is known regarding the genomic and clinical delineations of X-linked epilepsy in the Chinese population or the sex-stratified difference in epilepsy characteristics associated with deletions in the Xp22.31 region. In this study, we reported two siblings with a 1.69 Mb maternally inherited microdeletion at Xp22.31 involving the genes VCX3A, HDHD1, STS, VCX, VCX2, and PNPLA4 presenting with easily controlled focal epilepsy and language delay with mild ichthyosis in a Chinese family with a traceable 4-generation history of skin ichthyosis. Both brain magnetic resonance …

Powerful, Scalable And Resource-Efficient Meta-Analysis Of Rare Variant Associations In Large Whole Genome Sequencing Studies, Xihao Li, Corbin Quick, Hufeng Zhou, Sheila M. Gaynor, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Harald H. H. Goring, Michael Mahaney, Juan M. Peralta

School of Medicine Publications and Presentations

Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of …

Rescue Of Auditory Function By A Single Administration Of Aav-Tmprss3 Gene Therapy In Aged Mice Of Human Recessive Deafness Dfnb8, Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, Zheng-Yi Chen

Journal Articles: Genetics, Cell Biology & Anatomy

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3^A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. …

Determinism V. Free Will & Genetic Evidence Of Addiction In Plea Bargaining And Sentence Mitigation: Conversion Of Incarceration To Probation And Rehabilitation Based On Genetic Addiction Risk Severity (Gars) Test, Kenneth Blum, Paul Mullen, Richard Green

St. Mary's Law Journal

In this Article, Dr. Kenneth Blum and his team present the case of a presently abstinent, thirty-five year old alcoholic (“AG”) who has several convictions for DWI. AG has undergone and continues to be engaged in out-patient substance abuse treatment. He entered treatment before adjudication and was mandated by the court to continue treatment to assist in maintaining sobriety. Treatment included the administration of the Genetic Addiction Risk Severity (“GARS”) Test.

AG was facing a probable five-year sentence for his fifth DWI conviction in Bexar County, Texas. However, because AG’s genetic risk results indicated a genetically induced dopamine dysfunction, hypodopaminergia, …

Methods Development In Inflammatory Bowel Disease, Andrew B. Steimke

Theses and Dissertations (ETD)

Inflammatory bowel disease (IBD) is a disease that is classified into two subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). Symptoms can range from mild discomfort to requiring surgical intervention and affects approximately 1-in-200 adults in America alone, with global incidence rates increasing. While many treatments exist for IBD, perhaps the main reason for the lack of a cure is that there are many different pathogeneses that all lead to a very similar expression of symptoms. Over 240 IBD loci have been identified to date, yet the causative allele that drives the association has only been identified in ~60 of …

Identifying And Minimizing Underspecification In Breast Cancer Subtyping, Jonathan Cheuk-Kiu Tang

Master's Theses

In the realm of biomedical technology, both accuracy and consistency are crucial to the development and deployment of these tools. While accuracy is easy to measure, consistency metrics are not so simple to measure, especially in the scope of biomedicine where prediction consistency can be difficult to achieve. Typically, biomedical datasets contain a significantly larger amount of features compared to the amount of samples, which goes against ordinary data mining practices. As a result, predictive models may fail to find valid pathways for prediction during training on such datasets. This concept is known as underspecification.

Underspecification has been more accepted …

A Cloning-Free Recyclable System For Crispr-Cas9 Mediated Mutant And Reversion Construction In Candida Albicans Clinical Isolates, Amanda K. Vogel

Theses and Dissertations (ETD)

Candida albicans is a ubiquitous opportunistic fungal pathogen and one of the most prevalent causes of fungal diseases worldwide. The reference isolate SC5314 is one of the most widely used strains for both experimental and genetic studies, but it is becoming increasingly evident that genetic diversity in clinical isolates plays an important role in antifungal resistance, virulence, and pathogenicity. These recent discoveries highlight the need for genetic tools that are capable of investigating genes in multiple strain backgrounds. Here we build on the SAT1-flipper method and combine it with CRISPR-Cas9 technology to achieve cloning-free homozygous deletion in a single transformation …

North American Genetic Counselors' Approach To Collecting And Using Ancestry In Clinical Practice, Alexandra Hubbel, Elizabeth Hogan, Anne Matthews, Aaron Goldenberg

Student Scholarship

Current guidelines from the National Society of Genetic Counselors (NSGC) recommend that patients' ancestry be obtained when taking a family history. However, no study has explored how consistently genetic counselors obtain or utilize this information. The goals of this study included assessing how genetic counselors collect their patients' ancestry, what factors influence this decision, and how they view the utility of this information. Genetic counselors working in a direct patient care setting in the US or Canada were recruited to participate in an anonymous survey via an NSGC email blast. Most participants (n = 115) obtain information about their patients' …

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

Should Health Systems Share Genetic Findings With At-Risk Relatives When The Proband Is Deceased? Interviews With Individuals Diagnosed With Lynch Syndrome, Jessica Ezzell Hunter, Jennifer L. Schneider, Alison J. Firemark, James V. Davis, Sara Gille, Pamala A. Pawloski, Su-Ying Liang, Victoria Schlieder, Alanna Kulchak Rahm

Journal of Patient-Centered Research and Reviews

Purpose: Genetic information has health implications for patients and their biological relatives. Death of a patient before sharing a genetic diagnosis with at-risk relatives is a missed opportunity to provide important information that could guide interventions to minimize cancer-related morbidity and mortality in relatives.

Methods: We performed semi-structured interviews with individuals diagnosed with Lynch syndrome at 1 of 4 health systems to explore their perspectives on whether health systems should share genetic risk information with relatives following a patient’s death. An inductive, open-coding approach was used to analyze audio-recorded content, with software-generated code reports undergoing iterative comparative analysis by a …

Mismatch In Mice And Men, Ryan Schroeder, Hayley Ulloa, Alan Williams, Ed Grabczyk

Medical Research Day

Friedreich ataxia is a progressive degenerative neuromuscular disease that is caused by the expansion of a repetitive region of DNA, composed of three nucleotide repeats (GAA•TTC). Expansion of the DNA occurs throughout the lifespan of the patient and has been linked to the activity of specific DNA mismatch repair proteins. Disease onset occurs when the expansion increases in size beyond a certain threshold, silencing the gene and causing progressive ataxia, diabetes mellitus, and cardiomyopathy. These symptoms are linked to an increased repeat number observed within the heart, pancreas, and brain relative to other tissues within an individual. Friedreich ataxia is …