Medical Genetics Commons^™

Banning Abortion In Cases Of Down Syndrome: Important Lessons For Advances In Genetic Diagnosis, Rebecca Reingold, Lawrence O. Gostin

Georgetown Law Faculty Publications and Other Works

In December 2017, Ohio passed into law legislation that prohibited physicians from performing abortions if the pregnant woman’s decision was influenced by her belief that the fetus has Down syndrome. Physicians who perform abortions in these cases would face fourth-degree felony charges and revocation of their medical license. No other state bans abortion specifically for Down syndrome, but several ban abortions in cases of genetic diseases. Lower courts have struck down most such laws, holding they violate the constitutional rights of women. In February 2018, a federal district court judge blocked enforcement of Ohio’s law pending a final ...

Effect Of Trinucleotide Repeats In The Huntington's Gene On Intelligence, Jessica K. Lee, Amy Conrad, Eric Epping, Kathy Mathews, Vincent Magnotta, Jeffrey D. Dawson, Peg Nopoulos

Stead Family Department of Pediatrics Publications

BACKGROUND: Huntington's Disease (HD) is caused by an abnormality in the HTT gene. This gene includes trinucleotide repeats ranging from 10 to 35, and when expanded beyond 39, causes HD. We previously reported that CAG repeats in the normal range had a direct and beneficial effect on brain development with higher repeats being associated with higher cognitive function. The current study now expands this line of inquiry to evaluate the effects of CAG repeat throughout the entire spectrum of repeats from 15 to 58.

METHODS: We evaluated brain function in children ages 6-18 years old. DNA samples were processed ...

Optimization Of Braf V600 Assay As A 2-Step Real-Time Pcr Protocol, Mimi Phuong

Master's Theses and Capstone Projects

The QClamp® BRAF Codon Specific Mutation Detection Kit is a real-time PCR assay for the detection of somatic mutations in codon 600 Valine at exon 15 in the BRAF gene which encodes the serine/threonine protein kinase, using purified DNA. The V600E mutation is the most common BRAF gene mutation found in human cancers. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. Mutations in this gene have been found in cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, papillary thyroid carcinoma, non-small-cell lung carcinoma, gastric cancer, and ...

Surfactant Deficiency Syndrome In An Infant With A C-Terminal Frame Shift In Abca3: A Case Report, Nour Akil, Anthony J. Fischer

Stead Family Department of Pediatrics Publications

Deficiency in ATP binding cassette A3 (ABCA3) causes neonatal respiratory distress, hypoxemic respiratory failure, and interstitial lung disease. ABCA3 transports phospholipids into the lamellar bodies of type II alveolar cells, a critical step in alveolar surfactant production. We report a term infant with ABCA3 surfactant deficiency syndrome with the E292V (c.875A>T; p.Glu292Val) mutation in trans with a novel C-terminal frame shift mutation (c.4938delC; p.Met1647fs). This mutation removes the final 58 amino acids and substitutes 33 incorrect amino acids. The frame shift spares membrane spanning and nucleotide binding domains, but disrupts a highly conserved C-terminal domain ...

Dystrophic Calcifications Point The Way-Unusual And Early Diagnostic Clue Of Conradi-Hünermann-Happle Syndrome, Kenneth Yu, Alexander T. Reid, Stephanie J T Chen, Rajiv M. Patel, Steven M. Donn, Johann E. Gudjonsson, Lori Lowe

Stead Family Department of Pediatrics Publications

No abstract provided.

Editing Out Five Serpina1 Paralogs To Create A Mouse Model Of Genetic Emphysema, Florie Borel, Huaming Sun, Marina Zieger, Andrew Cox, Brynn Cardozo, Weiying Li, Gabriella Oliveira, Airiel Davis, Alisha Gruntman, Terence R. Flotte, Michael H. Brodsky, Andrew M. Hoffman, Mai K. Elmallah, Christian Mueller

Pediatric Publications and Presentations

Chronic obstructive pulmonary disease affects 10% of the worldwide population, and the leading genetic cause is alpha-1 antitrypsin (AAT) deficiency. Due to the complexity of the murine locus, which includes up to six Serpina1 paralogs, no genetic animal model of the disease has been successfully generated until now. Here we create a quintuple Serpina1a-e knockout using CRISPR/Cas9-mediated genome editing. The phenotype recapitulates the human disease phenotype, i.e., absence of hepatic and circulating AAT translates functionally to a reduced capacity to inhibit neutrophil elastase. With age, Serpina1 null mice develop emphysema spontaneously, which can be induced in younger mice ...

Complete Genome Sequences Of Three Staphylococcus Pseudintermedius Strains Isolated From Botswana, Mohamed Adel Salaheldin Abouelkhair, Stephen A. Kania, David A. Bemis, Matthew C. Riley, Riley Thompson

Faculty Publications and Other Works -- Biomedical and Diagnostic Sciences

We report here the first whole-genome sequences for 3 strains of Staphylococcus pseudintermedius (112N, 113N, and 114N) isolated in Africa. Samples of this opportunistic pathogen were collected from nasal swabs obtained from healthy carrier dogs in Botswana. The sequence information will facilitate spatial phylogenetic comparisons of staphylococcal species and other bacteria at the genome level.

Novel Candidate Genes Important For Asthma And Hypertension Comorbidity Revealed From Associative Gene Networks, Olga V. Saik, Pavel S. Demenkov, Timofey V. Ivanisenko, Elena Yu. Bragina, Maxim B. Freidin, Irina A. Goncharova, Victor E. Dosenko, Olga I. Zolotareva, Ralf Hofestaedt, Inna N. Lavrik, Evgeny I. Rogaev, Vladimir A. Ivanisenko

Open Access Articles

BACKGROUND: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or ~ 22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been ...

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic ...

Studying Vascular Morphologies In The Aged Human Brain Using Large Autopsy Datasets, Eseosa T. Ighodaro

Theses and Dissertations--Neuroscience

Cerebrovascular disease is a major cause of dementia in elderly individuals, especially Black/African Americans. Within my dissertation, we focused on two vascular morphologies that affect small vessels: brain arteriolosclerosis (B-ASC) and multi-vascular profiles (MVPs). B-ASC is characterized by degenerative thickening of the wall of brain arterioles. The risk factors, cognitive sequelae, and co-pathologies of B-ASC are not fully understood. To address this, we used multimodal data from the National Alzheimer’s Coordinating Center, Alzheimer’s Disease Neuroimaging Initiative, and brain-banked tissue samples from the University of Kentucky Alzheimer’s Disease Center (UK-ADC) brain repository. We analyzed two age at ...

Biosocial Criminology Versus The Constitution, Karen E. Balter

All Regis University Theses

The continually emerging field of biosocial criminology provides a basis for productively merging biology with sociological reasonings for criminal behavior. Mainstream research in criminology focuses on environmental factors as the sole reason individuals exhibit antisocial behavior patterns and may ultimately commit crimes. Criminological research has travelled in this direction for decades. The current climate within this community subscribes heavily to the notion that biology has very little to do with why people behave the way they do, and if it did, government control would be the norm. The nature of biocriminology opens a door through which constitutional issues may enter ...

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create ...

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of ...

Development Of The Personal Genomics Industry, Jorge L. Contreras, Vikrant Deshmukh

Utah Law Faculty Scholarship

Today, numerous commercial services offer genetic testing, genotyping and genome sequencing services both to medical providers and directly to the public. Twenty-five years ago, such offerings would have been unthinkable, both in terms of cost and medical practice. This chapter describes the development of the personal genomics industry and its evolving business models and goals.

Access To Guideline-Recommended Pharmacogenomic Tests For Cancer Treatments: Experience Of Providers And Patients, Ann Chen Wu, Kathleen M. Mazor, Rachel Ceccarelli, Stephanie Loomer, Christine Y. Lu

Open Access Articles

Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers' and patients' experiences and views on test access as well as strategies used for gaining access. We interviewed clinicians who prescribed medications that should be guided by pharmacogenomic testing and patients who received those prescriptions. We organized the themes into the four dimensions suggested by the World Health Organization framework on access to medications and health technologies. Guideline-recommended pharmacogenomic tests for cancer care are generally ...

Genes To Predict Vo2max Trainability: A Systematic Review, Camilla J. Williams, Mark G. Williams, Nir Eynon, Kevin J. Ashton, Jonathan P. Little, Ulrik Wisloff, Jeff S. Coombes

Faculty of Health Sciences & Medicine Publications

Background:

Cardiorespiratory fitness (VO_2max) is an excellent predictor of chronic disease morbidity and mortality risk. Guidelines recommend individuals undertake exercise training to improve VO_2max for chronic disease reduction. However, there are large inter-individual differences between exercise training responses. This systematic review is aimed at identifying genetic variants that are associated with VO_2max trainability.

Methods:

Peer-reviewed research papers published up until October 2016 from four databases were examined. Articles were included if they examined genetic variants, incorporated a supervised aerobic exercise intervention; and measured VO_2max/VO_2peak pre and post-intervention.

Results:

Thirty-five articles describing 15 cohorts met ...

The Gene Smart Study: Method, Study Design, And Preliminary Findings, Yan Xu, Nir Eynon, Ioannis D. Papadimitriou, Jujiao Kuang, Fiona Munson, Oren Tirosh, Lannie O'Keefe, Lyn R. Griffiths, Kevin J. Ashton, Nuala Byrne, Yannis P. Pitsiladis, David J. Bishop

Faculty of Health Sciences & Medicine Publications

The gene SMART (genes and the Skeletal Muscle Adaptive Response to Training) Study aims to identify genetic variants that predict the response to both a single session of High-Intensity Interval Exercise (HIIE) and to four weeks of High-Intensity Interval Training (HIIT). While the training and testing centre is located at Victoria University, Melbourne, three other centres have been launched at Bond University, Queensland University of Technology, Australia, and the University of Brighton, UK. Currently 39 participants have already completed the study and the overall aim is to recruit 200 moderately-trained, healthy Caucasians participants (all males 18-45 y, BMI<30). Participants will undergo exercise testing and exercise training by an identical exercise program. Dietary habits will be assessed by questionnaire and dietitian consultation. Activity history is assessed by questionnaire and current activity level is assessed by an activity monitor. Skeletal muscle biopsies and blood samples will be collected before, immediately after and 3h post HIIE, with the fourth resting biopsy and blood sample taken after four weeks of supervised HIIT (3 training sessions per week). Each session consists of eight to fourteen 2-min intervals performed at the pre-training lactate threshold (LT) power plus 40 to 70% of the difference between pre-training lactate threshold (LT) and peak aerobic power (W_peak). A ...

Small Rna Teg49 Is Derived From A Sara Transcript And Regulates Virulence Genes Independent Of Sara In Staphylococcus Aureus, Adhar Manna, Samin Kim, Liviu Cengher, Anna Corvaglia, Stefano Leo, Patrice Francois, Ambrose L. Cheung

Open Dartmouth: Faculty Open Access Articles

Expression of virulence factors in Staphylococcus aureus is regulated by a wide range of transcriptional regulators, including proteins and small RNAs (sRNAs), at the level of transcription and/or translation. The sarA locus consists of three overlapping transcripts generated from three distinct promoters, all containing the sarA open reading frame (ORF). The 5= untranslated regions (UTRs) of these transcripts contain three separate regions 711, 409, and 146 nucleotides (nt) upstream of the sarA translation start, the functions of which remain unknown. Re- cent transcriptome-sequencing (RNA-Seq) analysis and subsequent characterization indicated that two sRNAs, teg49 and teg48, are processed and likely ...

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Pediatric Publications and Presentations

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create ...

Difatty Acyl-Conjugated Linear And Cyclic Peptides For Sirna Delivery, Hung Do, Meenakshi Sharma, Naglaa Salem El-Sayed, Parvin Mahdipoor, Emira Bousoik, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic difatty acyl linear and cyclic R5K2 peptide conjugates were synthesized by solid-phase peptide methods to enhance the interaction with the hydrophobic cellular phospholipid bilayer and to improve siRNA delivery and silencing. Binding to siRNA molecules was significantly less for the cyclic peptide conjugates. A gradual decrease was observed in the particle size of the complexes with increasing peptide/siRNA ratio for most of the synthesized peptides, suggesting the complex formation. Most of the complexes showed a particle size of less than 200 nm, which is considered an appropriate size for in vitro siRNA delivery. A number ...