Posters
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Medical Student
Academic Level (Author 1)
Medical Student
Presentation Type
Poster
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Neuroscience Research
Abstract Type
Research/Clinical
Abstract
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, social deficits, and highly restrictive sensory patterns which results from aberrant early-life central nervous system functioning. While ASD has been traditionally associated with molecular genetic alterations, emerging evidence underscores the role of environmental elements. In fact, pathologic genetic variations of key regulator genes coupled with environmental factors, such as: advanced maternal age, poor maternal health during pregnancy, gestational diabetes mellitus, and altered gut microbiome and/or secondary environmental challenges to the offspring in early childhood have all been attributed to increased risk of developing ASD. In efforts to understand the complex relationship of genetics and gut microbiome with ASD pathogenicity, the present study, we used GTEx Portal to understand the interlink between genes associated with ASD pathogenecity and the gut microbiome.
Methods: GTex Portal, EMBAse databases were investigated in the present study. Using SfariGene,14 genes with the highest association of ASD manifestations were classified as high confidence genes and thoroughly examined for body expression, chromosomal location, mechanism of action, and symptom manifestation.
Results: Based on the GTE Portal, genes such as SHANK3, NRXN1, SYNGAP1, DYRK1A, and CUL3 are most highly expressed elsewhere throughout the body. High confidence genes had the highest expression were observed in three brain regions. SHANK3 was expressed highly in the cerebellum. MECP2, PTEN, SCN2A, NRXN1, and DYRK1A were expressed highly in the cerebellar hemisphere. CHD8, POGZ, and ANK2 had equal expressions in the cerebellum and cerebral hemisphere while CNTNAP2, TBR1, and GRIN2B were most highly expressed in the frontal cortex. SYNGAP1 and CUL3 had a wide variety of low expressions in most regions of the brain. High-impact genes, primarily regulators of gene expression, brain development, and connectivity, are commonly associated with intellectual disabilities, particularly in ASD. The most common manifestation was intellectual/cognitive disability, seen in 10 of 14 genes. Gut microbiome showed increased levels of p-cresol (4-methylphenol) due to widespread gastrointestinal bacterial activity, antibiotic overuse, and longer intestinal transit time, resulting in improper hippocampal neuronal development and neuronal mitochondria toxicity.
Conclusions: Based on our findings, the neurological mechanisms including- gene expression, brain development, and neural connectivity are the key pathways associated in the three key brain regions - cerebellum, cerebral hemisphere, and frontal cortex in ASD, However the wide variability in chromosomal deletions and manifestations underscores its complexity. GTex analysis suggests a foundation for developing potential novel tool to understand the interlink between gene expression in different brain regions and its implication in the gut microbial pathways in ASD.
Recommended Citation
Gullapalli, Sriya; Mourao, Nina; Sayers, Tori; Baldado, Lois; Szobody, Megan W.; Bellamkonda, Arjun; Martin, Blake C.; Punch, Kory D.; Valdez, Kevin Garcia; Murambadoro, Anesu Karen; Quintanilla, Miguel; Woolman, Bethany; Baker, Kelsey; and Gadad, Bharathi S., "Interlink between Genomics by GTEX Portal and Gut Microbiome in Autism Spectrum Disorder" (2025). Research Symposium. 157.
https://scholarworks.utrgv.edu/somrs/2025/posters/157
Interlink between Genomics by GTEX Portal and Gut Microbiome in Autism Spectrum Disorder
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, social deficits, and highly restrictive sensory patterns which results from aberrant early-life central nervous system functioning. While ASD has been traditionally associated with molecular genetic alterations, emerging evidence underscores the role of environmental elements. In fact, pathologic genetic variations of key regulator genes coupled with environmental factors, such as: advanced maternal age, poor maternal health during pregnancy, gestational diabetes mellitus, and altered gut microbiome and/or secondary environmental challenges to the offspring in early childhood have all been attributed to increased risk of developing ASD. In efforts to understand the complex relationship of genetics and gut microbiome with ASD pathogenicity, the present study, we used GTEx Portal to understand the interlink between genes associated with ASD pathogenecity and the gut microbiome.
Methods: GTex Portal, EMBAse databases were investigated in the present study. Using SfariGene,14 genes with the highest association of ASD manifestations were classified as high confidence genes and thoroughly examined for body expression, chromosomal location, mechanism of action, and symptom manifestation.
Results: Based on the GTE Portal, genes such as SHANK3, NRXN1, SYNGAP1, DYRK1A, and CUL3 are most highly expressed elsewhere throughout the body. High confidence genes had the highest expression were observed in three brain regions. SHANK3 was expressed highly in the cerebellum. MECP2, PTEN, SCN2A, NRXN1, and DYRK1A were expressed highly in the cerebellar hemisphere. CHD8, POGZ, and ANK2 had equal expressions in the cerebellum and cerebral hemisphere while CNTNAP2, TBR1, and GRIN2B were most highly expressed in the frontal cortex. SYNGAP1 and CUL3 had a wide variety of low expressions in most regions of the brain. High-impact genes, primarily regulators of gene expression, brain development, and connectivity, are commonly associated with intellectual disabilities, particularly in ASD. The most common manifestation was intellectual/cognitive disability, seen in 10 of 14 genes. Gut microbiome showed increased levels of p-cresol (4-methylphenol) due to widespread gastrointestinal bacterial activity, antibiotic overuse, and longer intestinal transit time, resulting in improper hippocampal neuronal development and neuronal mitochondria toxicity.
Conclusions: Based on our findings, the neurological mechanisms including- gene expression, brain development, and neural connectivity are the key pathways associated in the three key brain regions - cerebellum, cerebral hemisphere, and frontal cortex in ASD, However the wide variability in chromosomal deletions and manifestations underscores its complexity. GTex analysis suggests a foundation for developing potential novel tool to understand the interlink between gene expression in different brain regions and its implication in the gut microbial pathways in ASD.
