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Beyond The Basics: Unraveling The Complexity Of Coronary Artery Calcification, Satwat Hashmi, Pashmina Wiqar Shah, Zouhair Aherrahrou, Elena Aikawa, Rédouane Aherrahrou

Department of Biological & Biomedical Sciences

Coronary artery calcification (CAC) is mainly associated with coronary atherosclerosis, which is an indicator of coronary artery disease (CAD). CAC refers to the accumulation of calcium phosphate deposits, classified as micro- or macrocalcifications, that lead to the hardening and narrowing of the coronary arteries. CAC is a strong predictor of future cardiovascular events, such as myocardial infarction and sudden death. Our narrative review focuses on the pathophysiology of CAC, exploring its link to plaque vulnerability, genetic factors, and how race and sex can affect the condition. We also examined the connection between the gut microbiome and CAC, and the impact …

Phenotype And Genetic Analysis Of Data Collected Within The First Year Of Neurodev, Patricia Kipkemoi, Heesu Ally Kim, Bjorn Christ, Emily O’Heir, Jake Allen, Christina Austin-Tse, Samantha Baxter, Amina Abubakar, Charles Newton, Alicia Martin

Institute for Human Development

Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev’s first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing …

The Role Of Interspecies Recombination In The Evolution Of Antibiotic-Resistant Pneumococci, Joshua C. D'Aeth, Mark Pg Van Der Linden, Lesley Mcgee, Herminia De Lencastre, Paul Turner, Jae-Hoon Song, Stephanie W. Lo, Rebecca A. Gladstone, Gps Consortium, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking …

A Novel Mutation In The Choroideremia Gene In A Turkish Family., Mustafa Iftikhar, Yulia Wolfson, Simrat Sodhi, Bushra Usmani, Hendrik P. N. Scholl, Syed M.A. Shah

Medical College Documents

Choroideremia is an X-linked recessive genetic disorder caused by mutations in the CHM gene. It is a rare retinal dystrophy that manifests as nyctalopia and vision loss, progressing to blindness in later stages. We report a 21-year Turkish man who presented with nyctalopia for the past 4-5 years. His mother and maternal grandmother had similar, but less pronounced complaints. Fundus examination revealed pigmentary changes and retinal atrophy in both eyes. Optical coherence tomography showed outer retinal loss, with central island of preserved autofluorescence surrounded by absent autofluorescence on fundus autofluorescence examination. Goldmann visual fields were constricted. Microperimetry detected retinal sensitivity …

Subsequent Event Risk In Individuals With Established Coronary Heart Disease, Riyaz S. Patel, Vinicius Tragante, Amand F. Schmidt, Raymond O. Mccubrey, Michael V. Holmes, Laurence J. Howe, Kenan Direk, Axel Åkerblom, Karin Leander, Salim S. Virani

Office of the Provost

Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.
Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.
Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within …

Genetics Of The Thrombomodulin-Endothelial Cell Protein C Receptor System And The Risk Of Early-Onset Ischemic Stroke, John W. Cole, Huichun Xu, Kathleen Ryan,, Thomas Jaworek, Nicole Dueke, Patrick Mcardle, Brady Gaynor,, Yu-Ching Cheng, Jeffrey O'Connell, Ayeesha Kamran Kamal

Section of Neurology

Background and Purpose: Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.

Methods: Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms …

Large Scale Genetic Research On Neuropsychiatric Disorders In African Populations Is Needed, Shareefa Dalvie, Nastassja Koen, Laramie Duncan, Catherine Abbo, Dickens Akena, Lukoye Atwoli, Bonginkosi Chiliza, Kirsten A. Donald, Eugene Kinyanda, Christine Lochner

Internal Medicine, East Africa

In recent years there have been significant insights into the complex aetiologies of neurodevelopmental brain disorders. For example, neuropsychiatric genetics has achieved success with the identification of 108 loci for schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). Furthermore, meta-analyses of genomewide association study (GWAS) results encompassing thousands of samples have been completed for other psychiatric disorders including attention-deficit/hyperactivity disorder (ADHD), autism