Genetics and Genomics Commons^™

Challenges In Genetic Counseling In Hereditary Cancer Syndromes In A Mexican Oncologic Center, Diana Cristina Perez-Ibave, Diana Cristina De Lourdes Perez Ibave, María Fernanda Noriega-Iriondo, Omar Alejandro Zayas-Villanueva, Fernando Alcorta-Nuñez, Juan Francisco González-Guerrero, Adelina Alcorta-Garza, David Hernandez-Barajas, Oscar Vidal-Gutierrez, Carlos Horacio Burciaga-Flores

Research Symposium

Background: In Mexico, hereditary cancer is underdiagnosed, medical geneticists give genetic counseling, but the access is limited due to the socio-economic characteristics of the population. The CUCC (Centro Universitario Contra el Cáncer) Early Cancer Detection Clinic (CECIL) created a model in which patients without cancer are enrolled in a prevention cancer screening program.

Methods: From 2016 to 2021, 3014 patients were enrolled in the prevention program. Patients were evaluated with a hereditary cancer risk survey before a consultation. Those with at least one familial hereditary risk positive answer were assessed in a consultation. We also included patients with cancer diagnoses …

Repurposing Normal Chromosomal Microarray Data To Harbor Genetic Insights Into Congenital Heart Disease, Nephi Walton, Hoang Nguyen, Sara Procknow, Darren Johnson, Alexander Anzelmi, Patrick Jay

Department of Medicine Faculty Papers

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered …

In Vivo Crispr/Cas9 Screening Identifies Pbrm1 As A Regulator Of Myeloid Leukemia Development In Mice, Bin E Li, Grace Y Li, Wenqing Cai, Qian Zhu, Davide Seruggia, Yuko Fujiwara, Christopher R Vakoc, Stuart H Orkin

Faculty, Staff and Students Publications

CRISPR/Cas9 screening approaches are powerful tool for identifying in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which the sequential acquisition of somatic mutations generates clonal diversity. Over time, additional cooperating mutations may drive disease progression. Using an in vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We, first, modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs, followed by transplantation. We, then, performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and …

Rna World And The Development Of Rna Protocells, Benjamin C. Mayfield

PANDION: The Osprey Journal of Research and Ideas

Origins of life research, also known as pre-biotic chemistry or astrobiology, aims to unravel the mystery of the first cell’s origin on Earth. This interdisciplinary field encompasses biology, chemistry, and physics, with the primary goal of understanding the conditions necessary for life to emerge from abiotic environments. The RNA world hypothesis suggests that early life initially used RNA instead of DNA to store genomic information and for enzymatic functions. Protocells, membrane-bound entities with metabolic processes and self-replication capabilities, likely preceded the emergence of true cells. The challenges associated with RNA world is currently an active field of research. Advancements in …

The Localization Of Centromere Protein A Is Conserved Among Tissues, Eleonora Cappelletti, Francesca M. Piras, Lorenzo Sola, Marco Santagostino, Jessica L. Petersen, Rebecca R. Bellone, Carrie J. Finno, Sichong Peng, Ted S. Kalbfleisch, Ernest Bailey, Solomon G. Nergadze, Elena Giulotto

Department of Animal Science: Faculty Publications

Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence …

A Proteogenomics Data-Driven Knowledge Base Of Human Cancer, Yuxing Liao, Sara R Savage, Yongchao Dou, Zhiao Shi, Xinpei Yi, Wen Jiang, Jonathan T Lei, Bing Zhang

Faculty, Staff and Students Publications

By combining mass-spectrometry-based proteomics and phosphoproteomics with genomics, epi-genomics, and transcriptomics, proteogenomics provides comprehensive molecular characterization of cancer. Using this approach, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has characterized over 1,000 primary tumors spanning 10 cancer types, many with matched normal tissues. Here, we present LinkedOmicsKB, a proteogenomics data-driven knowledge base that makes consistently processed and systematically precomputed CPTAC pan-cancer proteogenomics data available to the public through ∼40,000 gene-, protein-, mutation-, and phenotype-centric web pages. Visualization techniques facilitate efficient exploration and reasoning of complex, interconnected data. Using three case studies, we illustrate the practical utility of LinkedOmicsKB in providing …

Allostatic Load Index Effectively Measures Chronic Stress Status In Zoo-Housed Giraffes, Haley N. Beer, Lisa K. Karr, Trenton C. Schrader, Dustin T. Yates

Department of Animal Science: Faculty Publications

For giraffes, few standardized methods exist for quantifying chronic stress. Allostatic load index is quantified from a panel of multi-system stress biomarkers to estimate cumulative stress. Our objective was to determine whether a panel of biomarkers selected for their role in allostatic load would reflect the number of documented stress events experienced by giraffes. Cortisol, DHEA-S, cholesterol, non-esterified fatty acids (NEFA), and fructosamine were determined in serum samples from zoo-housed giraffes (n = 18). These were correlated with the overall number and frequency of ZIMS-documented stress events experienced prior to blood collection. We also compared giraffes grouped by high vs. …

Sepepquant Enhances The Detection Of Possible Isoform Regulations In Shotgun Proteomics, Yongchao Dou, Yuejia Liu, Xinpei Yi, Lindsey K Olsen, Hongwen Zhu, Qiang Gao, Hu Zhou, Bing Zhang

Faculty, Staff and Students Publications

Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key …

A Multicenter Analysis Of Abnormal Chromosomal Microarray Findings In Congenital Heart Disease, Benjamin J Landis, Lindsey R Helvaty, Gabrielle C Geddes, Jiuann-Huey Ivy Lin, Svetlana A Yatsenko, Cecilia W Lo, William L Border, Stephanie Burns Wechsler, Chaya N Murali, Mahshid S Azamian, Seema R Lalani, Robert B Hinton, Vidu Garg, Kim L Mcbride, Jennelle C Hodge, Stephanie M Ware

Faculty, Staff and Students Publications

Background

Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype–phenotype relationships.

Methods and Results

Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers. Highly detailed cardiac phenotypes were systematically classified and analyzed for their association with CMA abnormality. Hierarchical classification of each patient into 1 CHD category facilitated broad analyses. Inclusive classification allowing multiple CHD types per …

Animal Board Invited Review: Practical Applications Of Genomic Information In Livestock, D. P. Berry, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Access to high-dimensional genomic information in many livestock species is accelerating. This has been greatly aided not only by continual reductions in genotyping costs but also an expansion in the services available that leverage genomic information to create a greater return-on-investment. Genomic information on individual animals has many uses including (1) parentage verification and discovery, (2) traceability, (3) karyotyping, (4) sex determination, (5) reporting and monitoring of mutations conferring major effects or congenital defects, (6) better estimating inbreeding of individuals and coancestry among individuals, (7) mating advice, (8) determining breed composition, (9) enabling precision management, and (10) genomic evaluations; genomic …

Diversity And Distribution Of Ascidians, Lauren M. Stefaniak

Marine Science

My research focuses on the biodiversity and biogeography of ascidians, the mechanisms controlling the distribution of species and communities, and how human activities, such as shipping, coastal hardening, and climate changes can alter those distributions. Working with my masters and undergraduate student researchers, I use morphological and molecular taxonomy, molecular ecology, and observational and manipulative field and lab studies to explore these questions...

This article was published Open Access through the CCU Libraries Transformative Agreement Program. The article was first published in genesis, the Journal of Genetics and Development: https://doi.org/10.1002/dvg.23548

Single Cell Multiomics Identifies Cells And Genetic Networks Underlying Alveolar Capillary Dysplasia, Minzhe Guo, Kathryn A Wikenheiser-Brokamp, Joseph A Kitzmiller, Cheng Jiang, Guolun Wang, Allen Wang, Sebastian Preissl, Xiaomeng Hou, Justin Buchanan, Justyna A Karolak, Yifei Miao, David B Frank, William J Zacharias, Xin Sun, Yan Xu, Mingxia Gu, Pawel Stankiewicz, Vladimir V Kalinichenko, Jennifer A Wambach, Jeffrey A Whitsett

Faculty, Staff and Students Publications

Rationale

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal developmental disorder of lung morphogenesis caused by insufficiency of FOXF1 (forkhead box F1) transcription factor function. The cellular and transcriptional mechanisms by which FOXF1 deficiency disrupts human lung formation are unknown.

Objectives

To identify cell types, gene networks, and cell–cell interactions underlying the pathogenesis of ACDMPV.

Methods

We used single-nucleus RNA and assay for transposase-accessible chromatin sequencing, immunofluorescence confocal microscopy, and RNA in situ hybridization to identify cell types and molecular networks influenced by FOXF1 in ACDMPV lungs.

Measurements and Main Results

Pathogenic single-nucleotide variants and copy-number …

Broken Tails In Holstein Dairy Cattle: A Cross-Sectional Study, Hannah E. Olsen, Karly N. Anderson, Katherine C. Creutzinger, Kurt D. Vogel

Department of Animal Science: Faculty Publications

Dairy cows are regularly handled when moved to the milking parlor and during other routine procedures. Low-stress handling methods are important in avoiding negative welfare states for dairy cattle. Tail twisting is used by some handlers to prompt cattle movement. However, when used inappropriately with excessive force, tail twisting can lead to a broken tail. The aim of this cross-sectional study was to determine cow-level factors that may be associated with the prevalence of broken tails in dairy cattle. A subset of 229 Holstein dairy cows (68 primiparous and 161 multiparous) at a single dairy were assessed for broken tails …

Gut Barrier Defects, Intestinal Immune Hyperactivation And Enhanced Lipid Catabolism Drive Lethality In Ngly1-Deficient Drosophila, Ashutosh Pandey, Antonio Galeone, Seung Yeop Han, Benjamin A Story, Gaia Consonni, William F Mueller, Lars M Steinmetz, Thomas Vaccari, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not …

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Collagene Enables Privacy-Aware Federated And Collaborative Genomic Data Analysis, Wentao Li, Miran Kim, Kai Zhang, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Growing regulatory requirements set barriers around genetic data sharing and collaborations. Moreover, existing privacy-aware paradigms are challenging to deploy in collaborative settings. We present COLLAGENE, a tool base for building secure collaborative genomic data analysis methods. COLLAGENE protects data using shared-key homomorphic encryption and combines encryption with multiparty strategies for efficient privacy-aware collaborative method development. COLLAGENE provides ready-to-run tools for encryption/decryption, matrix processing, and network transfers, which can be immediately integrated into existing pipelines. We demonstrate the usage of COLLAGENE by building a practical federated GWAS protocol for binary phenotypes and a secure meta-analysis protocol. COLLAGENE is available at https://zenodo.org/record/8125935 …

Early Onset Horizontal Gaze Palsy And Progressive Scoliosis Due To A Noncanonical Splicing-Site Variant And A Missense Variant In The Robo3 Gene, Sheng Yi, Zailong Qin, Xunzhao Zhou, Junjie Chen, Shang Yi, Qiuli Chen, Limei Huang, Qinle Zhang, Biyan Chen, Jingsi Luo

Faculty, Staff and Student Publications

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified.

METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene.

RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention …

Phasedancer: A Novel Targeted Assembler Of Segmental Duplications Unravels The Complexity Of The Human Chromosome 2 Fusion Going From 48 To 46 Chromosomes In Hominin Evolution, Barbara Poszewiecka, Krzysztof Gogolewski, Justyna A Karolak, Paweł Stankiewicz, Anna Gambin

Faculty, Staff and Students Publications

Resolving complex genomic regions rich in segmental duplications (SDs) is challenging due to the high error rate of long-read sequencing. Here, we describe a targeted approach with a novel genome assembler PhaseDancer that extends SD-rich regions of interest iteratively. We validate its robustness and efficiency using a golden-standard set of human BAC clones and in silico-generated SDs with predefined evolutionary scenarios. PhaseDancer enables extension of the incomplete complex SD-rich subtelomeric regions of Great Ape chromosomes orthologous to the human chromosome 2 (HSA2) fusion site, informing a model of HSA2 formation and unravelling the evolution of human and Great Ape genomes.

Appendage Abnormalities In Spiders Induced By An Alternating Temperature Protocol In The Context Of Recent Advances In Molecular Spider Embryology, Teresa Napiorkowska, Julita Templin, Pawel Napiorkowski, Mark A. Townley

Faculty Publications

In the literature there are numerous reports of developmental deformities in arthropods collected in their natural habitat. Since such teratogenically affected individuals are found purely by chance, the causes of their defects are unknown. Numerous potential physical, mechanical, chemical, and biological teratogens have been considered and tested in the laboratory. Thermal shocks, frequently used in teratological research on the spider Eratigena atrica, have led to deformities on both the prosoma and the opisthosoma. In the 2020/2021 breeding season, by applying alternating temperatures (14 °C and 32 °C, changed every 12 h) for the first 10 days of embryonic development, …

Daily Injection Of The Β2 Adrenergic Agonist Clenbuterol Improved Poor Muscle Growth And Body Composition In Lambs Following Heat Stress-Induced Intrauterine Growth Restriction, Rachel L. Gibbs, Rebecca M. Swanson, Joslyn K. Beard, Zena M. Hicks, Micah S. Most, Haley Beer, Pablo C. Grijalva, Shawna M. Clement, Eileen Marks-Nelson, Ty B. Schmidt, Jessica Lynn Petersen, Dustin T. Yates

Department of Animal Science: Faculty Publications

Background: Intrauterine growth restriction (IUGR) is associated with reduced β2 adrenergic sensitivity, which contributes to poor postnatal muscle growth. The objective of this study was to determine if stimulating β2 adrenergic activity postnatal would rescue deficits in muscle growth, body composition, and indicators of metabolic homeostasis in IUGR offspring.

Methods: Time-mated ewes were housed at 40°C from day 40 to 95 of gestation to produce IUGR lambs. From birth, IUGR lambs received daily IM injections of 0.8 μg/kg clenbuterol HCl (IUGR+CLEN; n = 11) or saline placebo (IUGR; n = …