Looking for differences in copy number between blood and brain in sporadic amyotrophic lateral sclerosis

Muscle Nerve. 2011 Oct;44(4):492-8. doi: 10.1002/mus.22095. Epub 2011 Aug 8.

Abstract

Introduction: Most analyses of blood DNA in sporadic neuromuscular disorders have been inconclusive. This may be because some genetic variants occur only in brain tissue. We therefore looked for copy number variants (CNVs) in both blood and brain in patients with sporadic amyotrophic lateral sclerosis (SALS).

Methods: Genome-wide CNVs were compared in blood and brain from 32 SALS patients and from 26 normal (control) brains, using Affymetrix 6.0 arrays.

Results: There were 410 CNVs present in brain but not blood (somatic CNVs) in 94% of the patients (median 8 CNVs per patient). Twenty-four of the somatic CNVs were rare, were not found in control brains, and overlapped with genes.

Conclusions: Brain-specific CNVs may be common and appear to be present in a proportion of patients with SALS. The more detailed copy number analysis that is becoming available with massively parallel sequencing may uncover brain-specific CNVs that underlie some cases of SALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis* / blood
  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / pathology
  • Blood / metabolism*
  • Brain / metabolism*
  • DNA Copy Number Variations / genetics*
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods