Genomics Commons^™

Everything But The Lab Sink: Using 1,000 Phylogenomically Informative Markers To Resolve Historically Messy Species Groups In Anastrepha Fruit Flies (Diptera: Tephritidae), Kristie J. Schmidt

2023 Midwest Ecology & Evolution Conference

The genus Anastrepha (Diptera: Tephritidae) is long overdue for a major taxonomic revision. Of the 22 recognized species groups within Anastrepha, only ~5 are well supported clades. Molecular methods, such as traditionally used mitochondrial DNA markers, have been unsuccessful at elucidating relationships amongst Anastrepha species; therefore, a more robust phylogenomic tool is likely necessary. To accomplish this, we used Highly Multiplexed Amplicon-based Phylogenomics (HiMAP) to identify 1,000 phylogenomically informative nuclear markers. Post sequencing, we obtained data for 500+ amplicons for 90 Anastrepha spp. belonging to 18 Anastrepha species groups. Our findings agree with some aspects of the most recently …

Convergent Evolution Of Antifreeze Proteins In Two Insect Families Supported By Whole Genome And Gene Family Loci Analyses, Shaw Kagawa

2023 Midwest Ecology & Evolution Conference

Various Coleoptera (beetles) and Lepidoptera (moths) insects are known to produce highly active antifreeze peptides (AFPs), an adaptive trait that enabled them to avoid freezing and survive severe winters. These include the grain pest Tenebrio molitor (yellow mealworm), pine-boring Rhagium beetles, the fire-colored Dendroides beetles, a stag beetle, and the Choristoneura spruce budworms (moths). Insect AFPs are small peptides of ~8 to 15 kDa, consisting of several tandem 13-amino acid repeats of similar sequences, each ending with a conserved tripeptide Thr-Cys/aa-Thr motif, found to be important for ice binding. Except for the eastern spruce budworm, the evolutionary origin/s and process/es …

Novel Model For Tau Protein Expression And Function: The Honeybee Brain, Abdallah F. Sher

2023 Midwest Ecology & Evolution Conference

Scientists have long attempted to understand the mechanisms by which senescence occurs. Leading theories suggest that aging is an emergent property of natural selection’s prioritization of reproductive ability. Social insects, such as the honeybee (Apis mellifera) challenge this idea, separating colonies into reproductive and non-reproductive castes. Worker honeybees do not reproduce, suggesting that selection prioritizes tasks other than reproduction. Forager honeybees, for example, display improved cognitive and immune function compared to other behavioral phenotypes of bees, likely to support their ability to perform tasks such as navigating complex environments or making context-dependent decisions while foraging. Foragers are normally older honeybees, …

Geographic Analysis Of Sex Chromosome Polymorphism In The Virginian Wild Strawberry, Trezalka A. Budinsky

2023 Midwest Ecology & Evolution Conference

The evolution of sex chromosomes is a ubiquitous and essential diversifying mechanism in eukaryotes. Yet early stages of sex-chromosome differentiation are poorly understood. The subdioecious octoploid, Fragaria virginiana, provides a rare opportunity to study the beginnings of sex chromosome evolution due to its young, polymorphic ZW sex system. Females are ZW and males/hermaphrodites are ZZ. F. virginiana has a small sex-determining region (SDR) located on the female W chromosome that has undergone three transposition events between the strawberry's four subgenomes, resulting in three SDR haplotypes: alpha (the result of a first transposition and closest to a pre-sex chromosome ancestral …

Potential Loss Of Pheromone Receptors In The Red Milkweed Beetle, Tetraopes Tetrophthalmus (Coleoptera: Cerambycidae), Mathew A. Price

2023 Midwest Ecology & Evolution Conference

The family of longhorn beetles (Coleoptera: Cerambycidae) are characterized by their elongate antennae, which are well adapted for detecting volatile compounds. This makes them an ideal family to study odorant receptor genes (ORs), which are the rapidly evolving family of proteins that are used by insects to detect odors at the molecular level. Here, we present data on 48 ORs we have sequenced and annotated from an antennal transcriptome of a male red milkweed beetle, Tetraopes tetrophthalmus. In contrast to most cerambycids, T. tetrophthalmus is not known to produce long-range sex pheromones to attract or select mates; correspondingly, …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Be-03 Effects Of Dietary Iron On Taxonomic Composition And Function Of The Zebrafish Gut Microbiome, Megan D. Whisonant, Jeremiah L. Jackson, Sam L. Evans, Stuart Gordon Ph.D.

SC Upstate Research Symposium

A healthy gut microbiota is essential to promote host health and well-being, therefore, effects of dietary components on the gut microbiome are important to investigate as the gastrointestinal tract can be a major route of infection. Iron—an essential component of heme and iron-sulfur proteins—plays a central role in many biological activities, including oxygen transport and cellular respiration.

In particular, the iron homeostasis system is one of the best characterized due to iron's causative relationship with iron-deficiency anemia. Dietary iron supplementation is a commonly used treatment for iron deficiency anemia; however, the known direct impacts of iron on the gut microbiome …

Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).

Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Faculty, Staff and Student Publications

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …

Srtsim: Spatial Pattern Preserving Simulations For Spatially Resolved Transcriptomics, Jiaqiang Zhu, Lulu Shang, Xiang Zhou

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT)-specific computational methods are often developed, tested, validated, and evaluated in silico using simulated data. Unfortunately, existing simulated SRT data are often poorly documented, hard to reproduce, or unrealistic. Single-cell simulators are not directly applicable for SRT simulation as they cannot incorporate spatial information. We present SRTsim, an SRT-specific simulator for scalable, reproducible, and realistic SRT simulations. SRTsim not only maintains various expression characteristics of SRT data but also preserves spatial patterns. We illustrate the benefits of SRTsim in benchmarking methods for spatial clustering, spatial expression pattern detection, and cell-cell communication identification.

A Biallelic Frameshift Indel In Ppp1r35 As A Cause Of Primary Microcephaly, Moez Dawood, Gulsen Akay, Tadahiro Mitani, Dana Marafi, Jawid M Fatih, Alper Gezdirici, Hossein Najmabadi, Kimia Kahrizi, Jaya Punetha, Christopher M Grochowski, Haowei Du, Angad Jolly, He Li, Zeynep Coban-Akdemir, Fritz J Sedlazeck, Jill V Hunter, Shalini N Jhangiani, Donna Muzny, Davut Pehlivan, Jennifer E Posey, Claudia M B Carvalho, Richard A Gibbs, James R Lupski

Faculty, Staff and Student Publications

Protein phosphatase 1 regulatory subunit 35 (PPP1R35) encodes a centrosomal protein required for recruiting microtubule-binding elongation machinery. Several proteins in this centriole biogenesis pathway correspond to established primary microcephaly (MCPH) genes, and multiple model organism studies hypothesize PPP1R35 as a candidate MCPH gene. Here, using exome sequencing (ES) and family-based rare variant analyses, we report a homozygous, frameshifting indel deleting the canonical stop codon in the last exon of PPP1R35 [Chr7: c.753_*3delGGAAGCGTAGACCinsCG (p.Trp251Cysfs*22)]; the variant allele maps in a 3.7 Mb block of absence of heterozygosity (AOH) in a proband with severe MCPH (-4.3 SD at birth, -6.1 SD by …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Determination Of Feasibility And Plausibility Of Using Various Biological Samples For Remote Genetic Testing, Cole Farnsworth, Molly Henley, Walker Kay, Varos Victer Manukyan, Jonathon Reynolds, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Presentation Of Paired P- And Q-Arm Mosaic Deletions On Chromosome 18 Associated With Neuropsychiatric Symptoms, Jackson Nielsen, Laura Minor, John Dougherty Jr., Paige Moore, Kailee Edwards, Brandon Burrell, Jameson Williams, John A. Kriak, David W. Sant, Kyle B. Bills

Annual Research Symposium

No abstract provided.

Braf V600e-Mutant Cancers Treated With Vemurafenib Alone Or In Combination With Everolimus, Sorafenib, Or Crizotinib Or With Paclitaxel And Carboplatin (Vem-Plus) Study, Blessie Elizabeth Nelson, Jason Roszik, Filip Janku, David S Hong, Shumei Kato, Aung Naing, Sarina Piha-Paul, Siqing Fu, Apostolia Tsimberidou, Maria Cabanillas, Naifa Lamki Busaidy, Milind Javle, Lauren Averett Byers, John V Heymach, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Combined BRAF + MEK inhibition is FDA approved for BRAF V600E-mutant solid tumors except for colorectal cancer. However, beyond MAPK mediated resistance several other mechanisms of resistance such as activation of CRAF, ARAF, MET, P13K/AKT/mTOR pathway exist among other complex pathways. In the VEM-PLUS study, we performed a pooled analysis of four phase one studies evaluating the safety and efficacy of vemurafenib monotherapy and vemurafenib combined with targeted therapies (sorafenib, crizotinib, or everolimus) or carboplatin plus paclitaxel in advanced solid tumors harboring BRAF V600 mutations. When vemurafenib monotherapy was compared with the combination regimens, no significant differences in OS or …

Deepbend: An Interpretable Model Of Dna Bendability, Samin Rahman Khan, Sadman Sakib, M Sohel Rahman, Md Abul Hassan Samee

Faculty, Staff and Students Publications

The bendability of genomic DNA impacts chromatin packaging and protein-DNA binding. However, we do not have a comprehensive understanding of the motifs influencing DNA bendability. Recent high-throughput technologies such as Loop-Seq offer an opportunity to address this gap but the lack of accurate and interpretable machine learning models still remains. Here we introduce DeepBend, a convolutional neural network model with convolutions designed to directly capture the motifs underlying DNA bendability and their periodic occurrences or relative arrangements that modulate bendability. DeepBend consistently performs on par with alternative models while giving an extra edge through mechanistic interpretations. Besides confirming the known …

Discovery Of Highly Potent And Bmpr2-Selective Kinase Inhibitors Using Dna-Encoded Chemical Library Screening, Ram K Modukuri, Diana Monsivais, Feng Li, Murugesan Palaniappan, Kurt M Bohren, Zhi Tan, Angela F Ku, Yong Wang, Chandrashekhar Madasu, Jian-Yuan Li, Suni Tang, Gabriella Miklossy, Stephen S Palmer, Damian W Young, Martin M Matzuk

Faculty, Staff and Students Publications

The discovery of monokinase-selective inhibitors for patients is challenging because the 500+ kinases encoded by the human genome share highly conserved catalytic domains. Until now, no selective inhibitors unique for a single transforming growth factor β (TGFβ) family transmembrane receptor kinase, including bone morphogenetic protein receptor type 2 (BMPR2), have been reported. This dearth of receptor-specific kinase inhibitors hinders therapeutic options for skeletal defects and cancer as a result of an overactivated BMP signaling pathway. By screening 4.17 billion “unbiased” and “kinase-biased” DNA-encoded chemical library molecules, we identified hits CDD-1115 and CDD-1431, respectively, that were low-nanomolar selective kinase inhibitors of …

Additional Taxonomic Refinements Suggested By Genomic Analysis Of Butterflies, Jing Zhang, Qian Cong, Jinhui Shen, Leina Song, Paul A. Opler, Nick V. Grishin

The Taxonomic Report of the International Lepidoptera Survey

Comparative analyses of genomic data reveal further insights into the phylogeny and taxonomic classification of butterflies presented here. As a result, 2 new subgenera and 2 new species of Hesperiidae are described: Borna Grishin, subgen. n. (type species Godmania borincona Watson, 1937) and Lilla Grishin, subgen. n. (type species Choranthus lilliae Bell, 1931) of Choranthus Scudder, 1872, Cecropterus (Murgaria) markwalkeri Grishin, sp. n. (type locality in Mexico: Sonora), and Hedone yunga Grishin, sp. n. (type locality in Bolivia: Yungas, La Paz). The lectotype is designated for Aethilla toxeus Plötz, 1882. The type locality of Dion uza (Hewitson, 1877) is likely …

A Comparison Of Microsatellites And Single Nucleotide Polymorphisms For The Assessment Of Population Structure In The Amblyomma Maculatum Koch, 1844 Species Complex, Henrey A. Deese

Electronic Theses and Dissertations

The Gulf Coast tick, Amblyomma maculatum Koch, 1844 is widespread throughout North and Central America and is the primary vector for the emerging pathogen Rickettsia parkeri. In the U.S., the population in the Southwest (A. maculatum morphotype III) is morphologically different from the population east of the Rocky Mountains (A. maculatum morphotype II). This research tests the hypothesis that A. maculatum morphotype II and morphotype III represent distinct species through the analysis and comparison of 6 microsatellite loci and suite of 135,221 Single nucleotide polymorphisms (SNPs) generated from ddRADseq. Population genetic analysis of both microsatellites and SNPs …