Genetics and Genomics Commons^™

Small Variant Benchmark From A Complete Assembly Of X And Y Chromosomes, Justin Wagner, Nathan D Olson, Jennifer Mcdaniel, Lindsay Harris, Brendan J Pinto, David Jáspez, Adrián Muñoz-Barrera, Luis A Rubio-Rodríguez, José M Lorenzo-Salazar, Carlos Flores, Sayed Mohammad Ebrahim Sahraeian, Giuseppe Narzisi, Marta Byrska-Bishop, Uday S Evani, Chunlin Xiao, Juniper A Lake, Peter Fontana, Craig Greenberg, Donald Freed, Mohammed Faizal Eeman Mootor, Paul C Boutros, Lisa Murray, Kishwar Shafin, Andrew Carroll, Fritz J Sedlazeck, Melissa Wilson, Justin M Zook

Faculty, Staff and Students Publications

The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets. We show how complete assemblies can expand benchmarks to difficult regions, but highlight …

Increased Positive Tree Species Mixture Effects On The Abundance And Richness Of Collembola With Stand Development In Canadian Boreal Forests, Yakun Zhang, Sai Peng, Zilong Ma, Chen Chen, Bilei Gao, Xinli Chen, Han Y.H. Chen

Aspen Bibliography

It is well established that species mixtures could enhance ecosystem functioning in diverse ecosystem types, with these benefits increasing over time. However, the impact of tree mixtures on Collembola communities following stand development in natural forests remains unclear, despite the critical roles Collembola plays in litter decomposition and nutrient cycling. We investigated the effects of tree species mixtures on Collembola abundance, diversity, and community structure by sampling pure and mixed jack pine (Pinus banksiana Lamb.) and trembling aspen (Populus tremuloides Michx.) of 15-year-old and 41-year-old stands in natural boreal forest. In total, 6,620 individuals of Collembola were identified …

Gene Model For The Ortholog Of Glys In Drosophila Simulans, Madeline L. Gruys, Madison A. Sharp, Zachary Lill, Caroline Xiong, Amy T. Hark, James J. Youngblom, Chinmay P. Rele, Laura K. Reed

Faculty Journal Articles

Gene model for the ortholog of glycogen synthase ( Glys ) in the Drosophila simulans May 2017 (Princeton ASM75419v2/DsimGB2) Genome Assembly (GenBank Accession: GCA_000754195.3 ). This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

Rpa And Rad27 Limit Templated And Inverted Insertions At Dna Breaks, Yang Yu, Xin Wang, Jordan Fox, Qian Li, Yang Yu, P J Hastings, Kaifu Chen, Grzegorz Ira

Faculty, Staff and Students Publications

Formation of templated insertions at DNA double-strand breaks (DSBs) is very common in cancer cells. The mechanisms and enzymes regulating these events are largely unknown. Here, we investigated templated insertions in yeast at DSBs using amplicon sequencing across a repaired locus. We document very short (most ∼5-34 bp), templated inverted duplications at DSBs. They are generated through a foldback mechanism that utilizes microhomologies adjacent to the DSB. Enzymatic requirements suggest a hybrid mechanism wherein one end requires Polδ-mediated synthesis while the other end is captured by nonhomologous end joining (NHEJ) or by alternative end joining (Alt-EJ). This process is exacerbated …

Investigating The Thermodynamic Properties Of Fat10 And Fat10ylated Proteins, Aravind R

Theses and Dissertations

Degradation of proteins by the proteasome is crucial in regulating protein levels in the cell. Post-translational modifications, such as ubiquitylation and Fat10ylation, trigger proteasomal degradation of the substrate proteins. While ubiquitylation orchestrates multiple cellular processes, Fat10ylation is primarily involved in the inflammatory response. Unlike ubiquitin, recycled upon substrate degradation, Fat10 is degraded along with its substrate. Although the thermodynamic properties of the substrate are critical for effective proteasomal degradation, they remain poorly understood for the Fat10-proteasome pathway.

Here, we demonstrate that Fat10 exhibits markedly lower thermodynamic stability and faster unfolding kinetics compared to ubiquitin. This is due to the absence …

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

All ETDs from UAB

Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …

St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva

All ETDs from UAB

The sialyltransferase ST6GAL1 is overexpressed in several cancers, including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane proteins, modifying their structure and function. Despite extensive research on how ST6GAL1 affects cell phenotype, the mechanisms regulating its expression remain largely unexplored. In this study, we investigated how two pro-inflammatory cytokines, IL-1β and IL-6, prevalent in the PDAC tumor microenvironment, regulate ST6GAL1 expression. We used the Suit-2 PDAC cell line and its metastatic subclones, S2-013 and S2-LM7AA, to monitor cytokine activity. Treatment with IL-1β or IL-6 increased ST6GAL1 protein and mRNA expression across all cell models. Specifically, …

Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church

All ETDs from UAB

Modification of pre-mRNA splicing using antisense oligonucleotides (ASOs) can be used to skip one or more exons carrying pathogenic DNA sequence variants. Our previ-ously published data indicates NF1 exon 52 is a good target for exon skipping as a cDNA screen indicates an NF1 isoform lacking exon 52 maintains both high neurofi-bromin expression and the ability to suppress Ras activity. To develop an exon skipping approach, we designed antisense phosphorodiamidate morpholino oligomers (PMOs) to skip exon 52. Our lead PMO has a low IC50 of 45nM and is able to restore NF1 expres-sion and Ras-suppression in a cell line with …

Plural Molecular And Cellular Mechanisms Of Pore Domain, Timothy J Abreo, Emma C Thompson, Anuraag Madabushi, Kristen L Park, Heun Soh, Nissi Varghese, Carlos G Vanoye, Kristen Springer, Jim Johnson, Scotty Sims, Zhigang Ji, Ana G Chavez, Miranda J Jankovic, Bereket Habte, Aamir R Zuberi, Cathleen M Lutz, Zhao Wang, Vaishnav Krishnan, Lisa Dudler, Stephanie Einsele-Scholz, Jeffrey L Noebels, Alfred L George, Atul Maheshwari, Anastasios Tzingounis, Edward C Cooper

Faculty, Staff and Students Publications

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. Kcnq2G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal …

Atrx Silences Cartpt Expression In Osteoblastic Cells During Skeletal Development, Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee

Faculty, Staff and Students Publications

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture …

Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data. Accordingly, we generate Meta-EA ensemble scores that achieve comparable performance to the top individual predicting method for each gene set. Incorporating the effects of splicing and the allele frequency …

Measuring Spatial And Temporal Variation In Species Composition Of Ephemeral Pond Amphibian Assemblages Using Metabarcoding, Elizabeth Strasko

Masters Theses & Specialist Projects

Amphibian populations worldwide face severe threats, heightening the need for reliable monitoring methods. In this thesis, I explored and tested environmental DNA (eDNA) metabarcoding protocols to survey amphibian assemblages in ephemeral ponds of the the Green River Preserve in central Kentucky, USA. First, I evaluated whether the commonly used mitochondrial cytochrome c oxidase subunit I (COI) gene could effectively capture species-level variation in local amphibians for eDNA metabarcoding. Extensive primer design and testing revealed significant challenges in amplifying fragmented eDNA from water samples. In a second study, I applied a metabarcoding approach using the mitochondrial 12S ribosomal RNA (12S) gene …

The Cdk8 Kinase Module: A Novel Player In The Transcription Of Translation Initiation And Ribosomal Genes, Brittany Friedson, Stephen D Willis, Natalia Shcherbik, Alicia N Campbell, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Survival following stress is dependent upon reprogramming transcription and translation. Communication between these programs following stress is critical for adaptation but is not clearly understood. The Cdk8 kinase module (CKM) of the Mediator complex modulates the transcriptional response to various stresses. Its involvement in regulating translational machinery has yet to be elucidated, highlighting an existing gap in knowledge. Here, we report that the CKM positively regulates a subset of ribosomal protein (RP) and translation initiation factor (TIF)-encoding genes under physiological conditions in Saccharomyces cerevisiae. In mouse embryonic fibroblasts and HCT116 cells, the CKM regulates unique sets of RP and TIF …

Determining Localization Of Surf-4 In Drosophila Melanogaster In The Secretory Pathway, Jada Scott

Mahurin Honors College Capstone Experience/Thesis Projects

The purpose of this research is to determine the role of the Surfeit-4 gene, or Surf-4 locus protein, during Drosophila melanogaster development. Surf-4 was identified in the Srivastava lab in a biochemical screen for proteins that associate with the basement membrane (BM): a structure needed and required for normal development and its degradation is a hallmark of tumor metastasis. Surf-4 has been predicted to function within intracellular compartments and is known to be expressed in many parts of the developing fly. We are currently determining why Surf-4 is important in development and what role, if any, it could play during …

Graduate Student Literature Review From "The Development Of The Brouwer Equation To Estimate Heat Production: Past, Present, And Future Perspectives" In Journal Of Dairy Science (2025), Addison L. Carroll, Paul J. Kononoff, Tami M. Brown-Brandl

Department of Animal Science: Faculty Publications

Appendix 1, supplemental to "The development of the Brouwer equation to estimate heat production: Past, present, and future perspectives," Journal of Dairy Science (2025).

Noncoding Rnas In Nuclear Organization, Thembalami Dube , '24, Dawn M. Carone

Biology Faculty Works

No abstract provided.

Covariate Selection For Rna-Seq Differential Expression Analysis With Hidden Factor Adjustment, Farzana Noorzahan, Hyeongseon Jeon, Yet Nguyen

Mathematics & Statistics Faculty Publications

In RNA-seq data analysis, a primary objective is the identification of differentially expressed genes, which are genes that exhibit varying expression levels across different conditions of interest. It is widely known that hidden factors, such as batch effects, can substantially influence the differential expression analysis. Furthermore, apart from the primary factor of interest and unforeseen artifacts, an RNA-seq experiment typically contains multiple measured covariates, some of which may significantly affect gene expression levels, while others may not. Existing methods either address the covariate selection or the unknown artifacts separately. In this study, we investigate two integrated strategies, FSR_sva and SVAall_FSR, …

Clonal Variation In Effector Gene Expression As A Mechanism For Pathogenic Adaptation In Magnaporthe Oryzae, Rebekah J. Ellsworth

Theses and Dissertations--Plant Pathology

Magnaporthe oryzae is a filamentous fungal pathogen that causes destructive diseases in cereals, including rice blast, wheat blast, and gray leaf spot. It is responsible for 10–30% annual yield losses in rice (Nalley et al., 2016) and up to 100% loss in wheat under favorable conditions (Kohli et al., 2011). Disease management typically relies on the use of resistant cultivars, but M. oryzae rapidly overcomes host resistance by mutating or deleting avirulence (AVR) genes recognized by host immune receptors. This rapid adaptation, often occurring within one to two growing seasons, presents a major challenge to breeding for durable resistance.

The …

Feasibility Of Producing Non-Structural Wood Products Using Trembling Aspen Lumber, Mengyuan Zhang

Aspen Bibliography

Trembling aspen (Populus tremuloides) is abundant in Canada but underutilized in non-structural solid wood products.This study was aimed at evaluating the feasibility of using aspen lumber to produce flooring, moulding, and siding. The shrinkage, surface roughness, and wettability of aspen wood were tested. The surface hardness, screw withdrawal resistance, colour change, and dimensional stability of there products fabricated were examined. The wood yield of each product was analyzed. It was found that aspen showed superior machinability and wettability to silver maple and yellow poplar. Aspen flooring had a Brinell hardness of 13.47 MPa, 60% lower than silver maple. …

Microsatellites Reveal The Population Genetic Structure Of Yellow Perch In Minnesota, Megan Boche

Journal of Earth and Life Science

When analyzing a population’s genetic makeup, looking at variation of individuals and populations is a crucial factor. The management of yellow perch will be aided by this information particularly in regard to stocking or relocation. Microsatellite loci were used to analyze the genetic population structure of yellow perch Perca flavescens within and among 29 sampling areas throughout Minnesota’s basins. Seven microsatellite DNA loci were evaluated, with heterozygosities ranging from 0.41 to 0.78. The Lower Mississippi basin samples showed higher numbers of alleles per locus and greater expected heterozygosities compared to other basins, with Lake Pepin (PEP) exhibiting the highest average …