We used whole exome sequencing (WES) to determine the genetic etiology of a patient with multi-system disorder characterized by seizure phenotype. WES identified heterozygous de novo missense mutation in GABRA1 gene (c.875C>T). encodes alpha subunit Gamma-Aminobutyric Acid receptor A (GABAAR). The GABAAR is ligand gated ion channel that mediates fast inhibitory signals nervous system and mutations sub-units compose have been previously associated human disease. To understand...

Abstract Erythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this can lead to anemia or thalassemia. The GATA1 transcription factor an established mediator of RBC development. However, upstream mechanisms that regulate expression not completely characterized. Cholesterol 1 potential because previously published studies suggest cholesterol synthesis disrupt differentiation. Here we characterize development a zebrafish harboring single missense mutation...

Recent efforts to engage postsecondary science, technology, engineering, and mathematics (STEM) students in the rigors of discovery-driven inquiry have centered on integration course-based undergraduate research experiences (CUREs) within biology curricula. While this method laboratory education is demonstrated improve students’ content knowledge, motivations, affect, persistence STEM, CUREs may present as cost- and/or resource-prohibitive. Likewise, not all lecture courses a concomitant...

Summary Inborn errors of cholesterol metabolism occur as a result mutations in the synthesis pathway (CSP). Although CSP cause multiple congenital anomaly syndrome, craniofacial abnormalities are hallmark phenotype associated with these disorders. Previous studies have established that mutation zebrafish hmgcs1 gene (Vu57 allele), which encodes first enzyme CSP, causes defects development and abnormal neural crest cell (NCC) differentiation. However, molecular mechanisms by products disrupt...

Abstract Background Heparan sulfate proteoglycan 2 ( HSPG2) encodes for perlecan, a large that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations HSPG2 have been associated with Schwartz-Jampel Syndrome (SJS) Dyssegmental Dysplasia Silverman-Handmaker Type (DDSH), two disorders characterized by skeletal abnormalities. These data indicate function development/maintenance. However, the mechanisms which regulates development are not...

Abstract Background Precise regulation of neural precursor cell (NPC) proliferation and differentiation is essential to ensure proper brain development function. The HCFC1 gene encodes a transcriptional co-factor that regulates proliferation, previous studies suggest NPC number differentiation. However, the molecular mechanism underlying these cellular deficits has not been completely characterized. Methods Here we created zebrafish harboring mutations in hcfc1a (the co60/+ allele), one...

Summary Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. encodes for α1 subunit gamma-aminobutyric acid type A receptor (GABA R), which regulates fast inhibitory impulses nervous system. Multiple model systems have previously been developed to understand function during development, but these models produced complex at times incongruent data. Thus, additional are required validate substantiate published results. We investigated behavioral swim patterns...

ZNF143 is a sequence-specific DNA binding protein that regulates the expression of protein-coding genes and small RNA molecules. In humans, interacts with HCFC1, transcriptional cofactor, to regulate downstream target genes, including MMACHC, which encodes an enzyme involved in cobalamin (cbl) metabolism. Mutations HCFC1 or cause inborn error metabolism characterized by abnormal cbl metabolism, intellectual disability, seizures, mild moderate craniofacial abnormalities. However, mechanisms...

Abstract Background: Precise regulation of neural precursor cell (NPC) proliferation and differentiation is essential to ensure proper brain development function. The HCFC1 gene encodes a transcriptional co-factor that regulates proliferation, previous studies suggest NPC However, the molecular mechanism underlying these cellular deficits has not been completely characterized. Methods: Here we created zebrafish harboring mutations in hcfc1a (the co60/+ allele), one ortholog utilized...

ABSTRACT We used whole exome sequencing (WES) to determine the genetic etiology of a patient with multi-system disorder characterized by seizure phenotype. WES identified heterozygous de novo missense mutation in GABRA1 gene (c.875C>T). GABRA 1 encodes alpha subunit Gamma-Aminobutyric Acid receptor A (GABA R). The GABA R is ligand gated ion channel that mediates fast inhibitory signals nervous system and mutations sub-units compose have been previously associated human disease. To...

Abstract Background Inborn errors of cholesterol metabolism occur as a result mutations in the synthesis pathway (CSP). Although CSP cause multiple congenital anomaly syndrome, craniofacial abnormalities are hallmark phenotype associated with these disorders. Previous studies have established that mutation zebrafish hmgcs1 gene (Vu57 allele), which encodes first enzyme CSP, causes defects development and abnormal neural crest cell (NCC) differentiation. However, molecular mechanisms by...

Variants in the MMACHC gene cause combined methylmalonic acidemia and homocystinuria cblC type, most common inborn error of intracellular cobalamin (vitamin B12) metabolism. is associated with neurodevelopmental, hematological, ocular, biochemical abnormalities. In a subset patients, mild craniofacial dysmorphia has also been described. Mouse models Mmachc deletion are embryonic lethal but severe phenotypes such as facial clefts. encodes an enzyme required for processing variants this result...

Abstract Erythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this can lead to anemia or thalassemia. The GATA1 transcription factor an established mediator of RBC development. However, upstream mechanisms that regulate expression not completely characterized. Cholesterol one potential because previously published studies suggest cholesterol synthesis disrupt differentiation. Here we characterize development a zebrafish harboring single missense...

Mutations in the HCFC1 transcriptional co‐factor cause cblX syndrome, an X‐linked disorder characterized by defects cobalamin metabolism, intractable epilepsy, microcephaly, intellectual disability, movement disorders, and craniofacial abnormalities. Intractable epilepsy neurological impairment are two of most severe phenotypes associated with however we do not understand cellular molecular mechanisms underlying these vivo . The human mouse orthologs located on X‐chromosome deletion murine...

Abstract Background: Precise regulation of neural precursor cell (NPC) proliferation and differentiation is essential to ensure proper brain development function. The HCFC1 gene encodes a transcriptional co-factor that regulates proliferation, previous studies suggest NPC However, the molecular mechanism underlying these cellular deficits has not been completely characterized. Methods : Here we created zebrafish harboring mutations in hcfc1a (the co60/+ allele), one ortholog , utilized...

Abstract Background : Heparan sulfate proteoglycan 2 ( HSPG2) encodes for perlecan, a large that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations HSPG2 have been associated with Schwartz-Jampel Syndrome (SJS) Dyssegmental Dysplasia Silverman-Handmaker Type (DDSH), two disorders characterized by skeletal abnormalities. These data indicate function development/maintenance. However, the mechanisms which regulates development are not...

Abstract Background : Heparan sulfate proteoglycan 2 ( HSPG2) encodes for perlecan, a large that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations HSPG2 have been associated with Schwartz-Jampel Syndrome (SJS) Dyssegmental Dysplasia Silverman-Handmaker Type (DDSH), two disorders characterized by skeletal abnormalities. These data indicate function development/maintenance. However, the mechanisms which regulates development are not...