Medical Genetics Commons^™

Analysis Of Positional Candidate Genes In The Aaa1 Susceptibility Locus For Abdominal Aortic Aneurysms On Chromosome 19, John H. Lillvis, Yoshiki Kyo, Gerard Tromp, Guy M. Lenk, Ming Li, Qing Lu, Robert P. Igo Jr, Natzi Sakalihasan, Robert E. Ferrell, Charles M. Schworer, Zoran Gatalica, Susan Land, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database.

Methods

Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. …

A Protein Network-Guided Screen For Cell Cycle Regulators In Drosophila, Stephen T. Guest, Jingkai Yu, Dongmei Liu, Julie A. Hines, Maria A. Kashat, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Large-scale RNAi-based screens are playing a critical role in defining sets of genes that regulate specific cellular processes. Numerous screens have been completed and in some cases more than one screen has examined the same cellular process, enabling a direct comparison of the genes identified in separate screens. Surprisingly, the overlap observed between the results of similar screens is low, suggesting that RNAi screens have relatively high levels of false positives, false negatives, or both.

Results

We re-examined genes that were identified in two previous RNAi-based cell cycle screens to identify potential false positives and false negatives. We …

Biomimetic Precipitation Of Uniaxially Grown Calcium Phosphate Crystals From Full-Length Human Amelogenin Sols, Vuk Uskoković, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

Human dental enamel forms over a period of 2 – 4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of a dense amelogenin matrix is presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aims to establish the physicochemical and biochemical conditions for the synthesis of fibrous apatite crystals under the control of a recombinant fulllength human amelogenin matrix in combination with a programmable titration system. The growth …

Regional Expression Of Hoxa4 Along The Aorta And Its Potential Role In Human Abdominal Aortic Aneurysms, John H. Lillvis, Robert Erdman, Charles M. Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A. Cox, Jianbin Shen, Richard S. Vander Heide, Guy M. Lenk, Leigh Hlavaty, Li Li, James R. Elmore, David P. Franklin, John L. Gray, Robert P. Garvin, David J. Carey, Wayne D. Lancaster, Gerard Tromp, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.

Results

We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic …

Approaches For Enhancing Therapeutic Efficacy Of A Novel Il-10 Gene Family Member: Mda-7/Il-24, Belal Azab

Theses and Dissertations

Melanoma differentiation associated gene-7 (mda-7) was discovered in the Fisher laboratory by subtraction hybridization of temporally spaced subtracted cDNA libraries prepared from terminally differentiated human melanoma cells treated with human fibroblast interferon (IFN-β) and the protein kinase C activator mezerein (MEZ), an approach called ‘differentiation induction subtraction hybridization’ (DISH). mda-7 is located in human chromosome 1q32–33 and based on sequence homology, chromosomal localization, and its functional properties, the mda-7 gene is now classified as a member of the IL-10 family of cytokines and named IL-24. The mda-7/IL-24 cDNA encodes a protein of 206-amino acids with a predicted size of ~24-kDa, …

Defining The Phenotypes Of Sickle Cell Disease., Samir K. Ballas

Department of Medicine Faculty Papers

The sickle cell gene is pleiotropic in nature. Although it is a single gene mutation, it has multiple phenotypic expressions that constitute the complications of sickle cell disease. The frequency and severity of these complications vary considerably both latitudinally in patients and longitudinally in the same patient over time. Thus, complications that occur in childhood may disappear, persist or get worse with age. Dactylitis and stroke, for example, occur mostly in childhood, whereas leg ulcers and renal failure typically occur in adults. It is essential that the phenotypic manifestations of sickle cell disease be defined accurately so that communication among …

Update On Pain Management In Sickle Cell Disease., Samir K Ballas

Department of Medicine Faculty Papers

Acute pain is the hallmark of sickle cell disease and is the most common cause of hospital admissions. Tissue damage due to vaso-occlusion releases numerous inflammatory mediators that initiate the transmission of painful stimuli that culminate in the perception of pain. The acute sickle cell painful crisis evolves along four phases. Each phase is coupled with changes in certain markers of the disease. Hospital readmission occurs within 1 week in about 16% of discharged patients and within 1 month in about 50% of discharged patients. Failure to treat acute pain aggressively may lead to chronic pain syndrome which, in turn, …

Current Review Of In Nivo Gbm Rodent Models: Emphasis On The Cns-1 Tumour Model, Valerie L. Jacobs, Pablo A. Valdes, William F. Hickey, Joyce A. De Leo

Dartmouth Scholarship

GBM (glioblastoma multiforme) is a highly aggressive brain tumour with very poor prognosis despite multi-modalities of treatment. Furthermore, recent failure of targeted therapy for these tumours highlights the need of appropriate rodent models for preclinical studies. In this review, we highlight the most commonly used rodent models (U251, U86, GL261, C6, 9L and CNS-1) with a focus on the pathological and genetic similarities to the human disease. We end with a comprehensive review of the CNS-1 rodent model.

Efficient Replication Of Over 180 Genetic Associations With Self-Reported Medical Data, Joyce Y. Tung, Chuong B. Do, David A. Hinds, Amy K. Kiefer, J. Michael Macpherson, Arnab B. Chowdry, Uta Francke, Brian Naughton, Joanna Mountain, Anne Wojcicki, Nicholas Eriksson

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for obtaining large amounts of medical information from a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we …

Genome-Wide Association Studies At The Interface Of Alzheimer’S Disease And Epidemiologically Related Disorders, Christopher Ryan Simmons

University of Kentucky Doctoral Dissertations

Genome-wide association studies (GWAS)s provide an unbiased means of exploring the landscape of complex genetic disease. As such, these studies have identified genetic variants that are robustly associated with a multitude of conditions. I hypothesize that these genetic variants serve as excellent tools for evaluation of the genetic interface between epidemiologically related conditions. Herein, I test the association between SNPs associated with either (i) plasma lipids, (ii) rheumatoid arthritis (RA) or (iii) diabetes mellitus (DM) and late-onset Alzheimer’s disease (AD) to identify shared genetic variants. Regarding the most significantly AD-associated variants, I have also attempted to elucidate their molecular function. …

Post-Transcriptional Regulation Of Afp And Igm Genes, Lilia M. Turcios

University of Kentucky Doctoral Dissertations

Gene expression can be regulated at multiple steps once transcription is initiated. I have studied two different gene models, the α-Fetoprotein (AFP) and the immunoglobulin heavy chain (IgM) genes, to better understand post-transcriptional gene regulation mechanisms. The AFP gene is highly expressed during fetal liver development and dramatically repressed after birth. There is a mouse strain-specific difference between adult levels of AFP, with BALB/cJ mice expressing 10 to 20-fold higher levels compared to other mouse strains. BALB/cJ mice express low levels of Zhx2 and thus incompletely repress AFP. Despite differences in steady state AFP mRNA levels in the adult liver …

Community Cancer Services, Clinical Trials, And Quality Initiatives—Year 1 Ncccp At Lehigh Valley Health Network, Gregory R. Harper Md, Phd, Ada M. Rivera Ba, Eliot L. Friedman Md, Kathleen A. Leies Rn, Ocn, Nadesda Mack Rn, Bsn, Mba, Ocn, Lenore Mcgonigle Med, Suresh G. Nair Md, Tara Namey Ms, Cgc, Debbie Salas-Lopez Md, Mph, Facp, Ronald W. Swinfard Md, Facp

Department of Medicine

No abstract provided.