Genetics Commons^™

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Predictive Screening Of M1 And M2 Macrophages Reveals The Immunomodulatory Effectiveness Of Post Spinal Cord Injury Azithromycin Treatment, John C. Gensel, Timothy J. Kopper, Bei Zhang, Michael B. Orr, William M. Bailey

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitrosystems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and …

A Rare Breed: Wild-Type Braf And Ighv Expression In A 29 Year Old Lady With Classical Hairy Cell Leukemia, A. Hossain, Hind Rafei, Amar Jariwala, Khaled El-Shami

Medicine Faculty Publications

The V600 BRAF mutation has been described as a key mutation in the pathogenesis of classical hairy cell leukemia (c-HCL) cases without expression of a mutant immunoglobulin heavy chain (IgHV). Here we present a rare case of c-HCL with neither V600 BRAF mutation nor the aforementioned IgHV variant successfully treated with cladribine and review the current literature on its use in women of childbearing age/pregnancy.

Medical Genetics And Genomic Medicine In The United States. Part 2: Reproductive Genetics, Newborn Screening, Genetic Counseling, Training, And Registries, Debra S. Regier, Carlos Ferreira, Suzanne Hart, Donald Hadley, Maximilian Muenke

Pediatrics Faculty Publications

eview of genetics in the United States with emphasis on the prenatal, metabolic, genetic counseling, and training aspects of the field.

Genetic Counselor Workforce Trends In The United States : 2002 To 2016, Charlene J. Schulz

Legacy Theses & Dissertations (2009 - 2024)

The purpose of this study was to identify and measure trends in genetic counselor (GC) workforce supply in the United States from 2002 to 2016. Using data collected biennially from the National Society of Genetic Counselors’ Professional Status Survey (PSS), I calculated overall percent change in GC employment across specific work settings over the past 14 years. I also measured change in the relative percentage of GCs who provide direct patient counseling (i.e. clinical GCs) to determine if the percentage of clinical GCs decreased over time. Analyses were performed to determine if associations existed between GC work settings and 1) …

Functions Of Atr/Mec1 In Meiosis And The Cell Cycle, Layne Weatherford

Wayne State University Dissertations

Mec1 is a protein kinase in S. cerevisiae that is critical for the DNA damage checkpoint response, and is the yeast orthologue of the human ATR protein. Cancer cells rely on ATR to arrest the cell cycle and allow sufficient time to repair DNA damage before proceeding through the cell cycle, and ATR inhibitors have been developed as possible anti-cancer agents. DBF4 is the regulatory subunit of DBF4-dependent kinase (DDK) that regulates initiation of DNA replication and is overexpressed in a number of different cancer types. To better understand ATR and DBF4 function, we took advantage of yeast genetics to …

Statistical Analyses To Detect And Refine Genetic Associations With Neurodegenerative Diseases, Yuriko Katsumata

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical state caused by neurodegeneration and characterized by a loss of function in cognitive domains and behavior. Alzheimer’s disease (AD) is the most common form of dementia. Although the amyloid β (Aβ) protein and hyperphosphorylated tau aggregates in the brain are considered to be the key pathological hallmarks of AD, the exact cause of AD is yet to be identified. In addition, clinical diagnoses of AD can be error prone. Many previous studies have compared the clinical diagnosis of AD against the gold standard of autopsy confirmation and shown substantial AD misdiagnosis Hippocampal sclerosis of aging (HS-Aging) …

Steroidogenesis In The Green Anole Lizard Brain And Gonad, Christine Peek

All Graduate Theses, Dissertations, and Other Capstone Projects

Seasonally breeding animals reproduce during certain times of the year and, subsequently, behaviors, steroid hormone levels, and brain morphology change. The green anole lizard (Anolis carolinensis) is an excellent model to study the regulation of steroid hormone production because they have distinct hormonal and behavioral differences between sexes and seasons. As in other vertebrates, steroidogenesis in anoles is under the control of the hypothalamus-pituitary-gonadal (HPG) axis. We tested the hypothesis that natural variations in steroid hormone levels between sexes and seasons are mediated within the brain and gonad by examining four genes involved in steroidogenesis: StAR, Cyp17α1, HSD17β3, and Cyp19α1. …

Paths To Tier 1 Genomics Implementation: A Survey Of Chronic Disease Directors, Amy Ponte

Walden Dissertations and Doctoral Studies

Although evidence is currently available for population-based genetic screening and testing of individuals and their family members for certain hereditary chronic disease conditions (Tier 1), few states have integrated these genomic applications into chronic disease prevention programs. State and territorial chronic disease directors (CDDs) could provide the leadership needed to deliver these applications in more states. The purpose of this study was to determine whether an association exists between current chronic disease genomics funding or specific state genomic activities and the level of knowledge and interests in genomics by these directors. Rogers's diffusion of innovations (DIT) theory was used to …

Living With Fragile X Syndrome: Occupations As An Outcome Measure In A Clinical Trial, Kaylee E. Gothelf, Ty Duong, Ana Baldinger, Theresa Chase

Student Research Posters

The purpose of this study was to evaluate the use of semi-structured interviews as an outcome measure in a clinical trial for children with fragile X syndrome (FXS) ages 2-6. This qualitative approach was used to analyze twenty-five interviews of parents with children in a double-blind medication trial - sertraline or placebo. The aim was to assess occupational improvements in their child that may not have been detected with the use quantitative outcome measures alone. Results showed greater improvements in the sertraline group in areas of behavior, social participation, sensory-related behaviors, receptive language, education, family impact and therapeutic strategies. Our …

Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki

Wayne State University Dissertations

The work of this project was to develop, test and characterize a potential novel mouse model of the neurodegenerative disease Multiple Sclerosis (MS). Historically, MS has been identified as a primary autoimmune disease of the central nervous system (CNS). However, treatments based on this view have met with limited success, and in most cases, fail to prevent progression of MS from mild to moderate and severe forms. Original observations regarding axonal and neuronal pathology in the white and gray matter of the CNS were rediscovered in the 1990s. These observations indicated that even in the absence of the immune system, …

Investigation On Genetic Modifiers Of Age At Onset Of Major Depressive Disorder, Huseyin Gedik

Theses and Dissertations

Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample …

Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan

Theses and Dissertations

DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic …

Drinking Motives Underlying Internalizing And Externalizing Pathways To Alcohol Misuse In College Students, Jeanne Savage

Theses and Dissertations

Alcohol misuse, including heavy episodic use and negative consequences, is a major public health concern and a particular problem among college students. The etiology of alcohol misuse is not well resolved, with multiple and often contradictory factors implicated in its development. Genetic factors influence alcohol misuse but few specific genes have been identified. A potential reason for these challenges is that alcohol misuse is phenotypically and genetically heterogeneous; that is, there are multiple causal pathways underlying its development. Previous typologies have suggested that distinct internalizing and externalizing pathways are involved, with corresponding differences in profiles of personality, temperament, and comorbid …

The Influence Of Genetic And Environmental Factors On Quit Attempt In Adolescent And Young Adult Twins, Gladys Langi

Theses and Dissertations

The purpose of this study was to examine the genetic and environmental influences on lifetime quit attempt in three US adolescent and young adult twin samples (N total = 6,322). The study utilized a common-contingent-causal (CCC) model to estimate these factors for lifetime quit attempts, after accounting for the factors for lifetime cigarette use and cigarettes per day. The study also examined age and sex differences, as well as the degree of relationship between these smoking phenotypes. The results demonstrated significant genetic influences for lifetime quit attempts in adolescents and young adults. No sex differences were observed for the contributions …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced …

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder

Dissertations and Theses (Open Access)

Over the last decade, a paradigm-shift in lung cancer therapy has evolved into targeted-driven medicinal approaches. However, patients frequently relapse and develop resistance to available therapies. Herein, we utilized genomic mutation data from advanced chemorefractory non-small cell lung cancer (NSCLC) patients enrolled in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) clinical trial to characterize novel actionable genomic alterations potentially of clinical relevance. We identified RICTOR alterations (mutations, amplifications) in 17% of lung adenocarcinomas and found RICTOR expression correlates to worse overall survival. There was enrichment of MAPK pathway genetic aberrations in key oncogenes (e.g. KRAS, BRAF, …

Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The recent studies have revealed that most BRAF inhibitors can paradoxically induce kinase activation by promoting dimerization and enzyme transactivation. Despite rapidly growing number of structural and functional studies about the BRAF dimer complexes, the molecular basis of paradoxical activation phenomenon is poorly understood and remains largely hypothetical. In this work, we have explored the relationships between inhibitor binding, protein dynamics and allosteric signaling in the BRAF dimers using a network-centric approach. Using this theoretical framework, we have combined molecular dynamics simulations with coevolutionary analysis and modeling of the residue interaction networks to determine molecular determinants of paradoxical activation. We …

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …

221 Newborn-Screened Neonates With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency: Findings From The Inborn Errors Of Metabolism Collaborative, K Bentler, S Zhai, S Elsbecker, G Arnold, B Burton, J Vockley, C Cameron, S Hiner, M Edick, S Berry, J Thomas, M Dodge, R Singh, S Lakshman, David Kronn, Inborn Errors Of Metabolism Collaborative

NYMC Faculty Publications

Introduction: There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods: Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism-Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results: The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcamitine (C8) value on first newborn screen was 11.2 …

Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff

Dissertations and Theses (Open Access)

Gene content determination and variant calling in the complex KIR genomic region are useful for immune system function analysis, pathogenesis and disease risk factor elucidation, immunotherapy development, evolutionary investigations, and human migration modeling. Sequence-specific oligonucleotide and sequence-specific primer PCR methods are the de facto standards for KIR presence/absence identification, but the current platforms are unsuitable for SNP calling, impractical for KIR typing large cohorts of DNA samples, and inapplicable for typing repositories in which sequence data, but not cells or cell analytes, are available. Alternative typing methods, such as in silico sequence-based typing, can address the problems associated with amplicon-based …

Relationship Between Morphogenesis And Secretion In The Filamentous Fungus Aspergillus Nidulans, Lakshmi Preethi Yerra

School of Biological Sciences: Dissertations, Theses, and Student Research

Filamentous fungi have a long history in biotechnology for the production of food ingredients, pharmaceuticals and enzymes. The advancements made in recent years have earned filamentous fungi such as Aspergillus species a dominant place among microbial cell factories. Although the model fungus A. nidulans has been extensively studied, the genetic and regulatory networks that underlie morphogenesis and development have yet to be fully characterized. The Rho GTPases (Cdc42 and RacA) are one of the most important regulators of the morphogenetic processes among diverse eukaryotic organisms. Although the functions of these GTPases are relatively well-characterized, little is known about their …

Identification Of Biomarkers Associated With Rous Sarcoma Virus-Induced Tumors In Two Divergently Selected Chicken Lines, Ashley Hayden

Graduate Theses and Dissertations

Poultry has become especially important to genetic research due to breeding feasibility, short generation turnover, and ease of maintaining large populations. The discovery of virus induced cancer has paved the way for further genetic studies. Rous Sarcoma Virus (RSV) is a tumor-causing virus that infects poultry. While not prevalent today, it can serve as a model for virus-induced cancer in humans and create additional insight to marker assisted selection in poultry. Genetically selected Arkansas Progressor (AP) and Arkansas Regressor (AR) chicken lines have been established and maintained at the Arkansas Experimental Station (AES) in Fayetteville, AR. Previous research has investigated …

The Clinical, Biochemical And Genetic Features Associated With Rmnd1-Related Mitochondrial Disease., Yi Shiau Ng, Charlotte L Alston, Daria Diodato, Andrew A Morris, Nicole Ulrick, Stanislav Kmoch, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, …

Adgrl3 (Lphn3) Variants Are Associated With A Refined Phenotype Of Adhd In The Mta Study, Maria T. Acosta, James Swanson, Annamarie Stehli, Brooke Molina, The Mta Team

Neurology Faculty Publications

Background

ADHD is the most common neuropsychiatric condition affecting individuals of all ages. Long-term outcomes of affected individuals and association with severe comorbidities as SUD or conduct disorders are the main concern. Genetic associations have been extensively described. Multiple studies show that intronic variants harbored in the ADGRL3 (LPHN3) gene are associated with ADHD, especially associated with poor outcomes.

Methods

In this study, we evaluated this association in the Multimodal Treatment Study of children with ADHD (MTA), initiated as a 14-month randomized clinical trial of 579 children diagnosed with DSM-IV ADHD-Combined Type (ADHD-C), that transitioned to a 16-year prospective observational …

Large Deletions At The Shox Locus In The Pseudoautosomal Region Are Associated With Skeletal Atavism In Shetland Ponies, Nima Rafati, Lisa S. Andersson, Sofia Mikko, Chungang Feng, Terje Raudsepp, Jessica Pettersson, Jan Janecka, Ove Wattle, Adam Ameur, Gunilla Thyreen, John E. Eberth, John Huddleston, Maika Malig, Ernest Bailey, Evan E. Eichler, Göran Dalin, Bhanu Chowdary, Leif Andersson, Gabriella Lindgren, Carl-Johan Rubin

Maxwell H. Gluck Equine Research Center Faculty Publications

Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure and impaired movements, and affected foals are usually killed. In order to identify the causal mutation we subjected six confirmed Swedish cases and a DNA pool consisting of 21 control individuals to whole genome resequencing. We screened for polymorphisms where the cases and the control pool were fixed for opposite alleles and observed this signature for only 25 SNPs, most of which were scattered on genome assembly unassigned scaffolds. …