title: Transcriptomic analyses of genes and tissues in inherited sensory neuropathies.
abstract: Inherited sensory neuropathies are caused by mutations in genes affecting either primary afferent neurons, or the Schwann cells that myelinate them. Using RNA-Seq, we analyzed the transcriptome of human and rat DRG and peripheral nerve, which contain sensory neurons and Schwann cells, respectively. We subdivide inherited sensory neuropathies based on expression of the mutated gene in these tissues, as well as in mouse TRPV1 lineage DRG nociceptive neurons, and across 32 human tissues from the Human Protein Atlas. We propose that this comprehensive approach to neuropathy gene expression leads to better understanding of the involved cell types in patients with these disorders. We also characterize the genetic "fingerprint" of both tissues, and present the highly tissue-specific genes in DRG and sciatic nerve that may aid in the development of gene panels to improve diagnostics for genetic neuropathies, and may represent specific drug targets for diseases of these tissues.
authors.affiliation: Department of Perioperative Medicine, Clinical Center, NIH, Bethesda, MD, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sapio
authors.affiliation: Department of Perioperative Medicine, Clinical Center, NIH, Bethesda, MD, USA.
authors.forename: Samridhi C
authors.initials: SC
authors.lastname: Goswami
authors.affiliation: Department of Perioperative Medicine, Clinical Center, NIH, Bethesda, MD, USA.
authors.forename: Jacklyn R
authors.initials: JR
authors.lastname: Gross
authors.affiliation: Department of Perioperative Medicine, Clinical Center, NIH, Bethesda, MD, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mannes
authors.affiliation: Department of Perioperative Medicine, Clinical Center, NIH, Bethesda, MD, USA. Electronic address: miadarol@cc.nih.gov.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology*; D059467:Transcriptome
chemical_list: D009097:Multienzyme Complexes; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase
keywords: Adipocytes; Charcot Marie Tooth; Dorsal root ganglion; Gene expression; Glia; HSAN; Inherited peripheral neuropathy; Myelin protein zero; Neuropathy; Pain; Pain channelopathy; Proprioception; RNA-Seq; Schwann cells; Sciatic nerve; Sodium channels; Spinal cord; TRPA1; TRPV1; Transcriptomics