A5015968575- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Retinal Imaging and Analysis
- Autism Spectrum Disorder Research
- Retinal Development and Disorders
- Complement system in diseases
- Genomic variations and chromosomal abnormalities
- Genetic Associations and Epidemiology
- HIV/AIDS drug development and treatment
- Genetics and Neurodevelopmental Disorders
- Mosquito-borne diseases and control
- Proteoglycans and glycosaminoglycans research
- Cystic Fibrosis Research Advances
- Ophthalmology and Visual Impairment Studies
- Heat shock proteins research
- Immune Response and Inflammation
- Neonatal Health and Biochemistry
- Virology and Viral Diseases
- Retinopathy of Prematurity Studies
- Retinoids in leukemia and cellular processes
- Gene expression and cancer classification
- Ferroelectric and Negative Capacitance Devices
- Cardiovascular Health and Risk Factors
- Digestive system and related health
- HIV-related health complications and treatments
Vanderbilt University Medical Center
2005-2024
Vanderbilt University
2007-2017
Meharry Medical College
2016
Center for Human Genetics
2004-2015
Genomics (United Kingdom)
2015
Massachusetts Eye and Ear Infirmary
2012
Harvard University
2012
Duke Medical Center
2005
Duke University
2005
Duke University Hospital
2005
Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring susceptibility locus for AMD. We used single-nucleotide polymorphisms to interrogate this region strongly associated haplotype two independent data sets. DNA resequencing complement factor H gene within revealed common coding variant, Y402H, that significantly increases risk AMD with odds...
Rationale: Up to 20% of cases idiopathic interstitial pneumonia cluster in families, comprising the syndrome familial (FIP); however, genetic basis FIP remains uncertain most families.Objectives: To determine if new disease-causing rare variants could be identified using whole-exome sequencing affected members from providing additional insights into disease pathogenesis.Methods: Affected subjects 25 kindreds were selected an ongoing registry for genomic DNA. Candidate confirmed by Sanger...
Age-related macular degeneration (AMD) is a retinal degenerative disease that the leading cause of blindness worldwide for individuals over age 60. Although etiology AMD remains largely unknown, numerous studies have suggested both genes and environmental risk factors significantly influence developing AMD. Identification underlying has been difficult, with genomic screen (locational) candidate gene (functional) approaches being used. The present study tested association AMD.Eight...
Age-related macular degeneration (AMD) is a devastating disorder of the central retina, causing significant visual impairment for 7.5 million elderly Americans. Abnormal regulation complement system likely caused by Y402H polymorphism in factor H gene recognized risk AMD, as A69S variant poorly characterized LOC387715 gene. Recently, polymorphisms B ( CFB ) and component 2 CC2 genes were associated with decreased susceptibility to AMD. To validate this association independent family-based...
Autism is a neurobehavioral spectrum of phenotypes characterized by deficits in the development language and social relationships patterns repetitive, rigid compulsive behaviors. Twin family studies point to significant genetic etiology, several groups have performed genomic linkage screens identify susceptibility loci. We genome-wide screen 158 combined Tufts, Vanderbilt AGRE (Autism Genetics Research Exchange) multiplex autism families using parametric nonparametric methods with...
Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, genome-wide association study (GWAS) for POAG an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm SNPs are associated our Caucasian US specific haplotypes located CAV1/CAV2 intergenic...
Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory suppressive capacity. However, heat-exposed helper 1 (T H 1) selectively developed mitochondrial stress DNA damage activated Trp53 stimulator interferon genes pathways. Although many subjected to such died, surviving exhibited...
Abstract Autism is a complex genetic neuropsychiatric condition characterized by deficits in social interaction and language patterns of repetitive or stereotyped behaviors restricted interests. Chromosome 15q11.2‐q13 candidate region for autism susceptibility based on observations chromosomal duplications small percentage affected individuals findings linkage association. We performed disequilibrium (LD) mapping across 1‐Mb interval containing cluster GABA A receptor subunit genes ( GABRB3...
Abstract Autism is a complex genetic neurodevelopmental disorder in which affected individuals display deficits language, social relationships, and patterns of compulsive stereotyped behaviors rigidity. Linkage analysis our dataset 57 New England 80 AGRE multiplex autism families reveals multipoint heterogeneity LOD (HLOD) score 2.74 at D17S1871 17q11.2. Analysis phenotypic subsets shows an increased HLOD 3.62 with The serotonin transporter locus ( SLC6A4 ) maps nearby considered functional...
Inflammation has long been suspected to play a role in the pathogenesis of age-related macular degeneration (AMD). Association variants complement factor H (CFH) and B (CFB) genes targeted search for additional loci alternative cascade, which C3 is major component. Two non-synonymous coding polymorphisms within C3, R102G L314P, have previously strongly associated with increased risk. These are strong linkage disequilibrium (LD), making contribution this locus AMD even more difficult...
The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is increased risk for age-related macular degeneration (AMD). A preliminary 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an occurrence 4917G compared controls (15.4% vs.9.0%, p = 0.11). Since there significant age difference between initial analysis, we extended...
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow aqueous humor through the trabecular meshwork causes pressure, but specific mechanisms are unknown. In this study, we used genome-wide SNP arrays map disease gene in colony Beagle dogs inherited POAG within single 4 Mb locus on canine chromosome 20. The syntenic previously mapped human quantitative trait for 19. Sequence...
Abstract Genome‐wide association studies (GWAS) are a useful approach in the study of genetic components complex phenotypes. Aside from large cohorts, GWAS have generally been limited to one or few diseases traits. The emergence biobanks linked electronic medical records (EMRs) allows efficient reuse data yield meaningful genotype–phenotype associations for multiple phenotypes Phase I MEdical Records and GEnomics (eMERGE‐I) Network is National Human Genome Research Institute‐supported...
Age-related macular degeneration (AMD) impairs vision for ∼7.5 million Americans. Both susceptibility variants and protective haplotypes in the complement factor H (CFH) gene modulate risk AMD. Recently, deletion of 'CFH-related' genes CFHR1 CFHR3 was found to be segregating with a particular CFH haplotype, which reduced We tested association Caucasian population 780 cases 265 controls examined its effect context known AMD factors. The did not segregate perfectly any one SNP, as previously...
To analyze the relationship between ARMS2 and HTRA1 in association with age-related macular degeneration (AMD) an independent case-control dataset to investigate subcellular localization of protein vitro system.Two SNPs were genotyped 685 cases 269 controls by a genotyping assay. Allelic was tested chi(2) test. A likelihood ratio test (LRT) full versus reduced models used interaction smoking smoking, after adjustment for CFH age. Immunofluorescence immunoblot applied localize retinal...
Primary open-angle glaucoma (POAG) is a common disease with complex inheritance. The identification of genes predisposing to POAG an important step toward the development novel gene-based methods diagnosis and treatment. Genome-wide association studies (GWAS) have successfully identified contributing traits such as however, frequently require very large sample sizes, thus, collaborations consortia been critical importance for GWAS approach. In this report we describe formation NEIGHBOR...
Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part our continued efforts define causes degeneration, we performed whole exome sequencing in four individuals two-generation family with autosomal dominant maculopathy identified rare variant p.Glu1144Lys Fibrillin 2 (FBN2),...
A major goal of personalized medicine is to pre-symptomatically identify individuals at high risk for disease using knowledge each individual's particular genetic profile and constellation environmental factors. With the identification several well-replicated factors age-related macular degeneration (AMD), leading cause legal blindness in older adults, this previously unreachable beginning seem less elusive. However, recently developed algorithms have either been much accurate than expected,...