A5076875985- Autism Spectrum Disorder Research
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Multiple Sclerosis Research Studies
- Folate and B Vitamins Research
- Genetic Associations and Epidemiology
- Retinal Development and Disorders
- vaccines and immunoinformatics approaches
- Cancer-related molecular mechanisms research
- Viral Infections and Immunology Research
- T-cell and B-cell Immunology
- Congenital heart defects research
- Cellular transport and secretion
- Neurological diseases and metabolism
- Lysosomal Storage Disorders Research
- Lipid metabolism and disorders
- Gene expression and cancer classification
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Ovarian cancer diagnosis and treatment
- Bioinformatics and Genomic Networks
- Growth Hormone and Insulin-like Growth Factors
- Nutrition, Genetics, and Disease
University of Miami
2012-2024
Dr. John T. Macdonald Foundation
2009-2016
Duke University Hospital
2001-2009
Center for Human Genetics
2009
Duke Medical Center
2001-2009
ID Genomics (United States)
2008
Duke University
2001-2006
Parkinson disease (PD) is a chronic neurodegenerative disorder with cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These implicated several genes as PD risk loci strong, but not significant, associations. In this study, we combined data from two previously published GWAS Caucasian subjects our 604 cases and 619 controls for joint analysis sample size 1752 1745...
Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous only fraction autism genes have been discovered. To help unravel this complexity, we performed whole exome sequencing on 100 individuals 40 families with...
Abstract Background Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, prioritization candidate genes and regions follow-up studies often proves difficult due to false-positive associations caused by statistical noise multiple-testing. In order address this issue, we propose novel GWAS reduction (GWAS-NR) method as a way increase power detect true in GWAS, particularly complex diseases such autism. Methods GWAS-NR...
Summary Although autism is one of the most heritable neuropsychiatric disorders, its underlying genetic architecture has largely eluded description. To comprehensively examine hypothesis that common variation important in autism, we performed a genome‐wide association study (GWAS) using discovery dataset 438 autistic Caucasian families and Illumina Human 1M beadchip. 96 single nucleotide polymorphisms (SNPs) demonstrated strong with risk (p‐value < 0.0001). The validation top SNPs was an...
Autism spectrum disorders (ASDs) are highly heritable, yet relatively few associated genetic loci have been replicated. Copy number variations (CNVs) implicated in autism; however, the majority of contribute to <1% disease population. Therefore, independent studies important refine CNV regions and discover novel susceptibility genes. In this study, a genome-wide SNP array was utilized for detection by two distinct algorithms European ancestry case–control data set. We identify significantly...
Genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) have consistently observed strong evidence with polymorphisms in APOE. However, until recently, variants at few other loci statistically significant associations replicated across studies. The present study combines data on 483,399 single nucleotide (SNPs) from a previously reported GWAS 492 LOAD cases and 496 controls an independent set 439 608 to strengthen power identify novel genetic signals. Associations...
Genome-wide association studies (GWASs) have proven highly effective, identifying hundreds of associations across numerous complex diseases. These typically test thousands variations and identify potential associations. However, to date, follow-up attempts generally only concentrated on just the few most significant initial associations, leaving majority true in any GWAS study without replication. Here, we present a substantially more comprehensive first genome-wide screen performed multiple...
Copy number variations (CNVs) are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than single nucleotide polymorphisms (SNPs). In multifaceted etiology autism spectrum disorders (ASDs), CNVs appear to contribute significantly our understanding pathogenesis this complex disease. A unique resource 42 extended ASD families was genotyped for over 1 million SNPs detect that may susceptibility. Each family has at least...
Background The Neuronal Ceroid Lipofuscinoses (NCL) comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify mutations associated with autosomal dominant disease (ADKD). Methodology and Principal Findings We have studied the family first reported this phenotype in 1970s, Parry family. proband had psychiatric manifestations, seizures cognitive decline starting her...
Autism spectrum disorder (ASD) is highly heritable, yet genome-wide association studies (GWAS), copy number variation screens, and candidate gene have found no single factor accounting for a large percentage of genetic risk. ASD trio exome sequencing revealed genes with recurrent de novo loss-of-function variants as strong risk factors, but there are relatively few recurrently affected while many 1000 predicted to play role. As such, it critical identify the remaining rare low-frequency...
Autism is a heritable neurodevelopmental disorder with substantial genetic heterogeneity. Studies point to possible links between autism and two serotonin related genes: SLC6A4 ITGB3 sex-specific effect interaction the genes. Despite positive findings, inconsistent results have complicated interpretation. This study seeks validate clarify previous findings in an independent dataset taking into account sex, family-history (FH) gene-gene effects. Family-based association analysis was performed...
Summary To identify novel late‐onset Alzheimer disease (LOAD) risk genes, we have analysed Amish populations of Ohio and Indiana. We performed genome‐wide SNP linkage association studies on 798 individuals (109 with LOAD). tested using the Modified Quasi‐Likelihood Score test also two‐point multipoint analyses. found that LOAD was significantly associated APOE ( P = 9.0 × 10–6) in all our ascertainment regions except for Adams County, Indiana, community 0.55). Genome‐wide, most strongly...
Summary Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), observation patients with mitochondrial defects have symptoms consistent ASD, there are no comprehensive published studies examining of variation autism. Therefore, we sought to comprehensively examine DNA (mtDNA) regard ASD risk, employing multi‐phase approach. In phase 1 our experiment, examined 132 mtDNA single‐nucleotide polymorphisms (SNPs)...
Abstract Background Autism spectrum disorder (ASD) is a complex neurodevelopmental with strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest presence X-linked susceptibility genes people ASD. Methods We analyzed genome-wide association study (GWAS) data on three independent autism GWAS sets: two family sets one case-control set. performed meta- joint analyses combined sets. In addition analyses, we...
Abstract Asperger disorder (ASP) is one of the autism spectrum disorders (ASD) and differentiated from largely on absence clinically significant cognitive language delays. Analysis a homogenous subset families with ASP may help to address corresponding effect genetic heterogeneity identifying ASD risk factors. To examine hypothesis that common variation important in ASD, we performed genome‐wide association study (GWAS) 124 discovery data set 110 validation set. We prioritized top 100...
The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced cancers. aim this study was to further delineate role IGFBP-2 pathoetiology and determine if reflected serum. Relative measured using quantitative real-time polymerase chain reaction 113 cancers 6 normal surface samples. Preoperative serum levels were by radioimmunoassay 84...
2-Methoxyestradiol (2-ME) is an estradiol metabolite with antiangiogenic and antitumor activity. It formed by granulosa cell (GC) catechol-O-methyltransferase activity present in the normal follicle at high concentrations. In this unique microenvironment, it may regulate selected types via autocrine and/or paracrine action. To assess possibility that 2-ME or might exert differential mitotic apoptotic effects on endothelial cells GCs, we compared their actions primary cultures of hormone-...
Background Essential tremor is a neurological condition characterized by during voluntary movement. To date, 3 loci linked to familial essential have been identified. Methods We examined 48 patients in 5 large pedigrees our data set for genetic linkage using an Affymetrix Axiom array. Linkage analysis was performed affecteds-only dominant model SIMWALK2. incorporate all genotype information, GERMLINE used identify genome segments shared identical-by-descent pairs of affecteds. Exome...
Abstract Chromosomal breaks and rearrangements have been observed in conjunction with autism autistic spectrum disorders. A chromosomal inversion has previously reported siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals associated disabilities. The containing strongly implicated linkage studies, particularly language defects as well other disorders components. Mapping of breakpoints FISH localized 99–108.75 Mb...