Transcriptomic analyses of genes and tissues in inherited sensory neuropathies

Exp Neurol. 2016 Sep;283(Pt A):375-395. doi: 10.1016/j.expneurol.2016.06.023. Epub 2016 Jun 23.

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.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Chromosome Mapping
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology*
  • Gene Expression / physiology
  • Gene Expression Profiling
  • Humans
  • In Vitro Techniques
  • Mixed Function Oxygenases / metabolism
  • Multienzyme Complexes / metabolism
  • Myelin Proteins / genetics
  • Myelin Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Organ Culture Techniques
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism*
  • Schwann Cells / pathology
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology*
  • Transcriptome*

Substances

  • Multienzyme Complexes
  • Myelin Proteins
  • Nerve Tissue Proteins
  • Mixed Function Oxygenases
  • peptidylglycine monooxygenase