Genetic Processes Commons^™

Meta-Analysis Of Genome-Wide Association Studies Identifies Ancestry-Specific Associations Underlying Circulating Total Tau Levels, Chloé Sarnowski, Mohsen Ghanbari, Joshua C Bis, Mark Logue, Myriam Fornage, Aniket Mishra, Shahzad Ahmad, Alexa S Beiser, Eric Boerwinkle, Vincent Bouteloup, Vincent Chouraki, L Adrienne Cupples, Vincent Damotte, Charles S Decarli, Anita L Destefano, Luc Djoussé, Alison E Fohner, Carol E Franz, Tiffany F Kautz, Jean-Charles Lambert, Michael J Lyons, Thomas H Mosley, Kenneth J Mukamal, Matthew P Pase, Eliana C Portilla Fernandez, Robert A Rissman, Claudia L Satizabal, Ramachandran S Vasan, Amber Yaqub, Stephanie Debette, Carole Dufouil, Lenore J Launer, William S Kremen, William T Longstreth, M Arfan Ikram, Sudha Seshadri

Faculty, Staff and Student Publications

Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P < 5 × 10-8. We additionally detected 14 novel loci at P < 5 × 10-7, specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer's, and Parkinson's (F5, MAP1B, and BCAS3), with Alzheimer's pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.

Human Genes Differ By Their Uv Sensitivity Estimated Through Analysis Of Uv-Induced Silent Mutations In Melanoma, Ivan P Gorlov, Christopher I Amos, Spiridon Tsavachidis, Colin Begg, Eva Hernando, Chao Cheng, Ronglai Shen, Irene Orlow, Li Luo, Marc S Ernstoff, Joel Parker, Nancy E Thomas, Olga Y Gorlova, Marianne Berwick

Faculty, Staff and Students Publications

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top …

Dna Transfer In The Soil Bacterium Rhodococcus, Jaimin Maheshbhai Kapadia

Undergraduate Honors Theses

Gene transfer plays an important role in bacterial evolution. Especially in an under explored species like Rhodococcus, a type of bacteria found in the soil. Rhodococcus has several applications in the pharmaceutical industry and in the production of antibiotics. Rhodococcus possess several unique sets of properties which makes it beneficial to have a reliable method of producing mutants of Rhodococcus. The goal of the experiment was to find an efficient way of forming Rhodococcus colonies with kanamycin resistant genes. The project began from an unexpected observation from an earlier experiment with Rhodococcus strain MTM3W5.2. where I attempted to transform this …

Novel Caries Loci In Children And Adults Implicated By Genome-Wide Analysis Of Families, Manika Govil, Nandita Mukhopadhyay, Daniel E. Weeks, Eleanor Feingold, John R. Shaffer, Steven M. Levy, Alexandre R. Vieira, Rebecca L. Slayton, Daniel W. Mcneil, Robert J. Weyant, Richard J. Crout, Mary L. Marazita

Faculty & Staff Scholarship

Background: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited.

Methods: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and …

Rare Single Gene Disorders: Estimating Baseline Prevalence And Outcomes Worldwide, Hannah Blencowe, Sowmiya Moorthie, Mary Petrou, Hanan Hamamy, Alan Bittles, Stephen Gibbons, Matthew Darlison, Bernadette Modell, Congenital Disorders Expert Group .

Research outputs 2014 to 2021

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and …

Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild

Pharmacy Faculty Articles and Research

Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.

Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …

El Acceso Y Uso De Las Pruebas Genéticas Para La Detección Precoz De Enfermedades Congénitas En Mujeres Embarazadas En La Ciudad Autónoma De Buenos Aires En El Año 2017 \ The Access And Use Of Genetic Tests For Early Detection Of Congenital Diseases In Pregnant Women In The Autonomous City Of Buenos Aires In The Year 2017, Anna Anna Bauer

Independent Study Project (ISP) Collection

Las pruebas genéticas son una herramienta útil para la prevención y el diagnóstico de defectos congénitos en las mujeres embarazadas. Esta investigación explora el acceso y uso de estas pruebas para mujeres que residen en la Ciudad Autónoma de Buenos Aires en el año 2017. Se trata de un tema amerita una investigación porque la tecnología para hacer estudios genéticos todavía es algo novedosa. Además, a través de las pruebas genéticas es posible detectar si el feto tiene un alto riesgo para desarrollar un defecto congénito, el cual es una de las causas más importantes de la mortalidad prenatal y …

Cohort Of Birth Modifies The Association Between Fto Genotype And Bmi, James Niels Rosenquist, Steven F. Lehrer, A. James O'Malley, Alan M. Zaslavsky, Jordan W. Smoller, Nicholas A. Christakis

Dartmouth Scholarship

A substantial body of research has explored the relative roles of genetic and environmental factors on phenotype expression in humans. Recent research has also sought to identify gene-environment (or g-by-e) interactions, with mixed success. One potential reason for these mixed results may relate to the fact that genetic effects might be modified by changes in the environment over time. For example, the noted rise of obesity in the United States in the latter part of the 20th century might reflect an interaction between genetic variation and changing environmental conditions that together affect the penetrance of genetic influences. To evaluate this …

The Metabolism Of Alcohol: Risk And Protective Factors, Sydney E. Levan, Amy Adkins, Danielle Dick, Karen G. Chartier

Undergraduate Research Posters

Purpose: Abstract for poster submission to VCU Poster Symposium for

Undergraduate Research and Creativity

Title: The Metabolism of Alcohol: Risk and Protective Factors

Background: In 2002, it was reported by the National Institutes of Health that

60.3% of college aged students (18-22) drank alcohol in the past month of being

asked, as compared to 51.9% of those not in college. They also found that 20% of

college students met the criteria for at least one alcohol use disorder (AUDs)1.

Many genes have been linked to an increased risk for AUDs and how individuals

with various ethnic backgrounds respond to alcohol. …

Epigenetics: Blurring The Line Between Nature And Nurture, Elizabeth H. Rose

CMC Senior Theses

This long-standing nature versus nurture debate is cited in behavioral and physical expressions of disease dysfunctions, resiliencies, and recovery. Their purposes are noted both in scientific pursuits as well as literature. This discourse has been particularly intense in the fields of psychology, psychiatry, and biology where there is a long history of scientists’ attempts to disprove or discredit others’ intellectual and professional measures. Interestingly, recent advances in the neurosciences and genetic technologies have brought these fields closer together with a new focus – the interactional relationship between nature and nurture – epigenetics.