Genetics and Genomics Commons^™

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …

An Investigation On The Irish Population’S Attitudes And Knowledge Towards Genetic Screening For Cancer, Emer Mccarthy, Ada Fleming, Dawn Hannah Cronin

International Undergraduate Journal of Health Sciences

Genetic mutations are alterations in DNA that may result in the development of a disease later in life. A BRCA gene is a tumour suppressor gene that helps to prevent the development of some cancers, particularly breast cancer. If a mutation occurs, this gene no longer functions at preventing these cancers. Genetic screening is when a population is tested for a mutation in an attempt to identify a group of people that are positive for the mutation. This can help identify cancer in different populations as well as track their inheritance. This study was conducted online, questioning the Irish populations …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

The Genes Of Pain, Alina Semenova

Thinking Matters Symposium

Pain is an important defense mechanism that protects us from environmental factors that might harm us. Our body's response to pain helps us to avoid injury. However, constant pain is a problem. Management of constant pain is an important area of research. Studies have shown that genetic variation contributes to pain sensitivity.

Numerous pain-related genes and their functional polymorphisms (CYP450, MOR-1, COMT, GCH1, etc.) have been identified in the past ten years. In particular, three opioid receptors (OPRM, OPRD and OPRK) are associated with pain sensitivity. One of the most studied human functional polymorphisms is the debrisoquine/sparteine polymorphism of CYP2D6 …

A Substitution In Cgmp-Dependent Protein Kinase 1 Associated With Aortic Disease Induces An Active Conformation In The Absence Of Cgmp, Matthew H Chan, Sahar Aminzai, Tingfei Hu, Amatya Taran, Sheng Li, Choel Kim, Renate B Pilz, Darren E Casteel

Faculty, Staff and Students Publications

Type 1 cGMP-dependent protein kinases (PKGs) play important roles in human cardiovascular physiology, regulating vascular tone and smooth-muscle cell phenotype. A mutation in the human PRKG1 gene encoding cGMP-dependent protein kinase 1 (PKG1) leads to thoracic aortic aneurysms and dissections. The mutation causes an arginine-to-glutamine (RQ) substitution within the first cGMP-binding pocket in PKG1. This substitution disrupts cGMP binding to the pocket, but it also unexpectedly causes PKG1 to have high activity in the absence of cGMP via an unknown mechanism. Here, we identified the molecular mechanism whereby the RQ mutation increases basal kinase activity in the human PKG1α and …

Genetic And Metabolomic Architecture Of Variation In Diet Restriction-Mediated Lifespan Extension In Drosophila., Kelly Jin, Kenneth A. Wilson, Jennifer N. Beck, Christopher S. Nelson, George W. Brownridge Iii, Benjamin R. Harrison, Danijel Djukovic, Daniel Raftery, Rachel B. Brem, Shiqing Yu, Mathias Drton, Ali Shojaie, Pankaj Kapahi, Daniel Promislow

Natural Sciences and Mathematics | Student Professional Publications

In most organisms, dietary restriction (DR) increases lifespan. However, several studies have found that genotypes within the same species vary widely in how they respond to DR. To explore the mechanisms underlying this variation, we exposed 178 inbred Drosophila melanogaster lines to a DR or ad libitum (AL) diet, and measured a panel of 105 metabolites under both diets. Twenty four out of 105 metabolites were associated with the magnitude of the lifespan response. These included proteinogenic amino acids and metabolites involved in α-ketoglutarate (α-KG)/glutamine metabolism. We confirm the role of α-KG/glutamine synthesis pathways in the DR response through genetic …

Association Of Interleukin 17f With Arthritis In Punjabi Families Of Pakistan, Asia Parveen, Andleeb Batool, Maryam Mukhtar, Abdul Wajid, Naila Malkani

Journal of Bioresource Management

Arthritis is a chronic inflammatory disease that causes severe joint pain. Interleukin 17F (IL17F) is considered as a candidate gene functionally; it mediates pro-inflammatory responses, depending on the type and site of inflammation. The present study examined the polymorphism of IL17F (rs763780 and rs2397084) among the families affected by arthritis. Demographic data and blood samples were collected from the families with at least one affected offspring with arthritis. Analysis of the IL17F gene polymorphism was performed by the digestion of DNA with NlaIII and AvaII. The results showed that IL17F rs763780 (AA, AG and GG genotypes) and rs2397084 (AA, AG …

Frontotemporal Dementia Nonsense Mutation Of Progranulin Rescued By Aminoglycosides, Lisha Kuang, Kei Hashimoto, Eric J. Huang, Matthew S. Gentry, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy.

Aminoglycosides are a class of antibiotics that possess a less known function …

Analysis Of Two Maize Mutations That Arose After Exposure To Radiation From A Plutonium-Beryllium Source And Developing Molecular Markers For Antimorph Aei1-5180, An Alternative To Aei To Increase Amylose Content In Maize Endosperm, Prameela Awale

Electronic Theses and Dissertations

This thesis consists of two independent projects dealing with two different aspects of maize. The first project is about the maize reproduction, where we try to uncover the candidate genes of two mutations that affect pollen viability and successful fertilization. The second project is about maize endosperm starch, where we developed molecular markers to characterize a mutant allele that knocks a major starch branching enzyme in maize.

Analysis of two maize mutations that arose after exposure to radiation from a plutonium-beryllium source
Maize is a monoecious and diclinous plant. Sexual reproduction takes place by the fusion of haploid male and …

Genetics With Nettie And Friends: An Exploration Of Genetics In Children's Literature, Erin Soule, Madeleine Gray Burland

Honors Projects

Genetics with Nettie and Friends is an exploration of chromosomal disorders and its place within children's literature. The book provides a comprehensive examination the genetic composition of Downs syndrome, Williams Syndrome, and Duchenne muscular dystrophy at a level to increase understanding in children. This paper provides an insight to the development and construction of the children's book that is available for purchase on Barnes and Noble as well as why representation of genetic disorders in children's literature is needed.

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu

Biochemistry Publications

Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were …

Multigenerational Genomic And Epigenetic Effects Of Manufactured Silver Nanomaterials In Caenorhabditis Elegans, Anye Wamucho

Theses and Dissertations--Toxicology and Cancer Biology

There has been an increase in the incorporation of silver nanomaterials into consumer products due to their antimicrobial properties. Therefore there is potential for silver nanoparticles (Ag-NPs) to leach out into the environment during different life-cycle stages of these nanomaterial-containing products. Concern about the toxicity of Ag-NPs has led to investigations into their toxic effects on a variety of organisms mainly using acute and sub-chronic, single-generation exposures. The focus of this project was to understand the effects of long-term continuous multigenerational exposure to AgNO₃ and Ag-NPs in both pristine and environmentally transformed forms, on the model organism, Caenorhabditis elegans …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

A Mutation Affecting Polycystin-1 Mediated Heterotrimeric G-Protein Signaling Causes Pkd, Stephen C. Parnell, Brenda S. Magenheimer, Robin L. Maser, Tengis S. Pavlov, Mallory A. Havens, Michelle L. Hastings, Stephen F. Jackson, Christopher J. Ward, Kenneth R. Peterson, Alexander Staruschenko, James P. Calvet

Biology Department Faculty Articles

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of renal cysts that ultimately destroy kidney function. Mutations in the PKD1 and PKD2 genes cause ADPKD. Their protein products, polycystin-1 (PC1) and polycystin-2 (PC2) have been proposed to forma calcium-permeable receptor-channel complex; however the mechanisms by which they function are almost completely unknown. Most mutations in PKD1 are truncating loss-of-function mutations or affect protein biogenesis, trafficking or stability and reveal very little about the intrinsic biochemical properties or cellular functions of PC1. An ADPKD patient mutation (L4132D or DL), resulting in a single amino acid deletion in a …

The Zinc Transporter Zipt-7.1 Regulates Sperm Activation In Nematodes, Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating …

Crispr Gene Editing In The Sea Squirt, Ciona Intestinalis, Evelyn Siler, Steven Irvine

Senior Honors Projects

Genetic manipulation has come a long way in the past ten years alone. Scientists have had access to gene editing techniques for decades, but until recently these methods have proven to be expensive and unpredictable. However, thanks to the development of a new, more efficient genome editing strategy called CRISPR/Cas9, more aggressive progress can now be made in genetics research.

CRISPR is not a machine or a physical tool, but rather it is a system that involves introducing a protein into a cell, along with a DNA segment that will attract the protein to a desired location on the DNA. …

Uvb Induced Mutation Of P53 In Non Melanoma Skin Cancer, Raizy Berger

The Science Journal of the Lander College of Arts and Sciences

There is a clear correlation between excessive sun exposure and the development of skin cancer. UVB radiation from the sun is potent, and as the ozone layer gets depleted, more UVB can reach Earth and cause cell damage. UV radiation causes DNA lesions, such as 6-4 photoproducts and cyclobutane pyrimidine dimers. Cyclobutane pyrimidine dimers are more abundant and take longer to be repaired and therefore are responsible for most of the mutation and DNA damage. These DNA lesions lead to mutation of the p53 gene. The signature mutation on p53 from UV radiation is a CC to TT mutation, which …

Identification Of The Cftr C.1666a > G Mutation In Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis, Yan Lu, Yuwei Da, Yong B. Zhang, Xingang Li, Min Wang, Li Di, Mi Pang, Lin Lei

Research outputs 2014 to 2021

Hereditary inclusion body myopathy (HIBM) is a rare autosomal recessive adult onset muscle disease which affects one to three individuals per million worldwide. This disease is autosomal dominant and occurs in adulthood. Our previous study reported a new subtype of HIBM linked to the susceptibility locus at 7q22.1-31.1. The present study is aimed to identify the candidate gene responsible for the phenotype in HIBM pedigree. After multipoint linkage analysis, we performed targeted capture sequencing on 16 members and whole-exome sequencing (WES) on 5 members. Bioinformatics filtering was performed to prioritize the candidate pathogenic gene variants, which were further genotyped by …

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …

Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer

Biological Sciences Faculty Publications

Viral gain-of-function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …

Mutations Of Conserved Non-Coding Elements Of Pitx2 In Patients With Ocular Dysgenesis And Developmental Glaucoma., Meredith E. Protas, Eric Weh, Tim Footz, Jay Kasberger, Scott C. Baraban, Alex V. Levin, L. Jay Katz, Robert Ritch, Michael A. Walter, Elena V. Semina, Douglas B. Gould

Natural Sciences and Mathematics | Faculty Scholarship

Mutations in FOXC1 and PITX2 constitute the most common causes of ocular anterior segment dysgenesis (ASD), and confer a high risk for secondary glaucoma. The genetic causes underlying ASD in approximately half of patients remain unknown, despite many of them being screened by whole exome sequencing. Here, we performed whole genome sequencing on DNA from two affected individuals from a family with dominantly inherited ASD and glaucoma to identify a 748-kb deletion in a gene desert that contains conserved putative PITX2 regulatory elements. We used CRISPR/Cas9 to delete the orthologous region in zebrafish in order to test the pathogenicity of …

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O⁶-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ω_ave. We found …

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

High Resolution Time-Course Mapping Of Early Transcriptomic, Molecular And Cellular Phenotypes In Huntington's Disease Cag Knock-In Mice Across Multiple Genetic Backgrounds., Seth A Ament, Jocelynn R Pearl, Andrea Grindeland, Jason St Claire, John C Earls, Marina Kovalenko, Tammy Gillis, Jayalakshmi Mysore, James F Gusella, Jong-Min Lee, Seung Kwak, David Howland, Min Young Lee, David Baxter, Kelsey Scherler, Kai Wang, Donald Geman, Jeffrey B Carroll, Marcy E Macdonald, George Carlson, Vanessa C Wheeler, Nathan D Price, Leroy Hood

Articles, Abstracts, and Reports

Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, …

Dna Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent Of Error-Prone Synthesis, And The Role Of Dntp Pools, Olga V. Kochenova

Theses & Dissertations

Despite multiple DNA repair pathways, DNA lesions can escape repair and compromise normal chromosomal replication, leading to genome instability. Cells utilize specialized low-fidelity Translesion Synthesis (TLS) DNA polymerases to bypass lesions and rescue arrested replication forks. TLS is a highly conserved two-step process that involves insertion of a nucleotide opposite a lesion and extension of the resulting aberrant primer terminus. The first step can be performed by both replicative and TLS DNA polymerases and, because of non-instructive DNA lesions, often results in a nucleotide misincorporation. The second step is almost exclusively catalyzed by DNA polymerase ζ …

Selfish Mutations: The Genetic Basis Of The Paternal Age Effect, Eoin C. Whelan

Biological Sciences Theses & Dissertations

As the mean age of childrearing grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father but have a deleterious effect in offspring.

I present a mathematical model to analyse the normal function of the stem cell compartment, which provides a framework for SSC renewal and accommodates differences between animal systems. In order to model the SSC mutation accumulation, a Markov chain …

Alcohol Discrimination And Preferences In Two Species Of Nectar-Feeding Primate, Samuel R. Gochman, Michael B. Brown, Nathaniel J. Dominy

Dartmouth Scholarship

Recent reports suggest that dietary ethanol, or alcohol, is a supplemental source of calories for some primates. For example, slow lorises (Nycticebus coucang) consume fermented nectars with a mean alcohol concentration of 0.6% (range: 0.0–3.8%). A similar behaviour is hypothesized for aye-ayes (Daubentonia madagascariensis) based on a single point mutation (A294V) in the gene that encodes alcohol dehydrogenase class IV (ADH4), the first enzyme to catabolize alcohol during digestion. The mutation increases catalytic efficiency 40-fold and may confer a selective advantage to aye-ayes that consume the nectar of Ravenala madagascariensis. It is uncertain, however, whether alcohol exists in this nectar …

Comprehensive Genetic Testing Identifies Targetable Genomic Alterations In Most Patients With Non-Small Cell Lung Cancer, Specifically Adenocarcinoma, Single Institute Investigation, Janani Vigneswaran, Yi-Hung Carol Tan, Septimiu D. Murgu, Brian M. Won, Kathryn Alexa Patton, Victoria M. Villaflor, Philip C. Hoffman, Thomas Hensing, D. Kyle Hogarth, Renuka Malik

Dartmouth Scholarship

This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular …