Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Molecular And Cellular Investigations Of Prader-Willi Syndrome, Anna K. Victor

Theses and Dissertations (ETD)

Prader-Willi syndrome (PWS) is a complex multigenic neurodevelopmental disorder resulting in hypotonia, developmental delay, hypogonadism, sleep dysfunction and childhood onset obesity affecting 1 in 10,000 to 30,000 individuals. PWS is an imprinting disorder that is caused by a loss of expression of maternally imprinted genes in the 15q11.2-q13 region including NDN, MAGEL2, SNRPN/SNURF, and a cluster of snoRNAs. The majority of cases are caused by inheriting a paternal allele deletion of this region (65-75%) and a smaller number are caused by chromosome 15 maternal uniparental disomy (UPD) (20-30%) or imprinting center defects (1-3%). Here, we used dental pulp stem cells …

The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle

Theses and Dissertations (ETD)

CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia in patients without Down syndrome (non-DS-AMKL) and is associated with an event free survival of only 8% even with high intensity chemotherapy and stem cell transplant in first remission. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified …

Genomic Characterization Of Sickle Cell Mouse Models For Therapeutic Genome Editing Applications, Kaitly Jensen Woodard

Theses and Dissertations (ETD)

Sickle cell disease (SCD) is caused by a mutation of the β-globin gene (HBB), resulting in abnormal hemoglobin molecules that polymerize when deoxygenated, forming “sickle” shaped red blood cells (RBCs). Sickle RBCs lead to anemia, multi-organ damage and pain crises, beginning the first year of life. The onset of symptoms coincides with the developmental switch of β-like globin gene expression from fetal stage γ-globin to adult stage β-globin, resulting in a shift from fetal hemoglobin (HbF, α2γ2) to adult hemoglobin (HbA, α2β2). Some individuals harbor rare genetic variants in the extended β-globin gene cluster that cause constitutively elevated postnatal HbF, …

The Health-Related Quality Of Life Of Adults With Down Syndrome, Rebecca Jermyn Graves

Theses and Dissertations (ETD)

Purpose. The purpose of this study was to examine the health-related quality of life (HRQOL) and factors associated with the HRQOL of adults with Down syndrome (DS) as reported by adults with DS and their caregivers. The study was designed to compare measures of HRQOL, health problems, health risks, and health-care utilization of adults with DS based on self-report with those from caregiver-report and to explore associations between HRQOL and health problems, health risks, health-care utilization, adaptive behavior, and demographic characteristics. Background. The life expectancy of individuals with DS has lengthened from approximately 30 years around 1960 to over 50 …

Phenotypic And Electrophysiologic Characterization Of A Mouse Model Of Fragile X Syndrome, Snigdha Roy

Theses and Dissertations (ETD)

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. It is caused by a mutation in the fragile X mental retardation (FMR1) gene on the X chromosome. Many children with FXS exhibit autistic behaviors and deficits in motor coordination including speech articulation deficits. The development of the FMR1 knockout (Fmr1 KO) mouse, in which the Fmr1 gene is inactivated, has provided an animal model that can be used to investigate underlying neuro-physiological mechanisms associated with FXS as well as to evaluate potential therapeutic treatments. In this study, quantitative behavioral assays were used, such as long term …

The Relationships Among Adaptive Behaviors Of Children With Autism Spectrum Disorder, Their Family Support Networks, Parental Stress, And Parental Coping, Heather Roberts Hall

Theses and Dissertations (ETD)

Purpose: The purpose of this study was to examine the adaptive behaviors of children with Autism Spectrum Disorder (ASD), their family support networks, parental stress, and parental coping and the relationships among these variables.

Background: Autism is the fastest growing diagnosed developmental disorder. When parents receive a diagnosis of autism for their child, mothers and fathers are affected differently. The costs to families of children with autism are personal, social, and affect family finances and day to day living. Parents of a child with autism are at high risk for increased stress levels. The child’s socially unacceptable behaviors and communication …

The Cystic Fibrosis Transmembrane Conductance Regulator: Regulation By Hsp-90, Kevin Marrs

Theses and Dissertations (ETD)

The hypothesis of this project is that a functionally relevant association exists between CFTR and Hsp90. In testing this hypothesis, (a) the association of CFTR and Hsp90 is confirmed via crosslinking and immunoprecipitation of CFTR from stably transfected HEK-293 cells, electrophoretic separation of cross-linked proteins, and protein identification via SDS-PAGE, western blotting, and mass spectrometry. Also, this hypothesis is tested by (b) functionally assessing the effect of Hsp90 on CFTR function via Ussing chamber analysis, two-electrode voltage clamp analysis, preliminary in vivoanimal studies, and protein phosphorylation. The HEK-293 Flag-CFTR cells used in this study allows for a high degree …