title: Structural variants can be more informative for disease diagnostics, prognostics and translation than current SNP mapping and exon sequencing.
abstract: BACKGROUND
  In this article we discuss several human neurological diseases and their relationship to specific highly polymorphic small structural variants (SVs). Unlike genome-wide association analysis (GWAS), this methodology is not a genome screen to define new possibly associated genes, requiring statistical corrections for a million association tests. SVs provide local mapping information at a specific locus. Used with phylogenetic analysis, the specific association of length variants can be mapped and recognized.
  
  
  METHODS
  This experimental strategy provides identification of DNA variants, particularly variable length Simple Sequence Repeats (SSRs or STRs or microsatellites) that provide specific local association data at the SV locus. Phylogenetic analysis that includes the specific appearance of different length SV variations can differentiate specific phenotypic risks in a population such as age of onset related to variable length polymorphisms and risk of phenotypic variations associated with several adjacent structural variations (SVs). We focus on data for three recent examples associated with Alzheimer's disease, Levy Bodies, and Parkinson's disease.
  
  
  CONCLUSIONS
  SVs are understudied, but have led directly to mechanism of pathogenesis studies involving the regulation of gene expression. The identification of specific length polymorphisms associated with clinical disease has led to translational advances and new drug discovery.
authors.affiliation: a Department of Neurology and Neurosciences , Duke University , Durham , NC , USA.|b Zinfandel Pharmaceuticals , Chapel Hill , NC , USA.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.affiliation: c Shiraz Pharmaceuticals, Inc , Chapel Hill , NC , USA.
authors.forename: P Anthony
authors.initials: PA
authors.lastname: Akkari
authors.affiliation: d Department of Neurology , Duke University , Durham , NC , USA.
authors.forename: Ornit
authors.initials: O
authors.lastname: Chiba-Falek
authors.affiliation: d Department of Neurology , Duke University , Durham , NC , USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lutz
authors.affiliation: d Department of Neurology , Duke University , Durham , NC , USA.
authors.forename: William Kirby
authors.initials: WK
authors.lastname: Gottschalk
authors.affiliation: d Department of Neurology , Duke University , Durham , NC , USA.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Saunders
authors.affiliation: e Polymorphic DNA , Alameda , CA , USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Saul
authors.affiliation: f Caberner Pharmaceuticals, Inc , Chapel Hill , NC , USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Sundseth
authors.affiliation: g Zinfandel Pharmaceuticals, Inc , Raleigh-Durham , NC , USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Burns
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D005091:Exons; D005786:Gene Expression Regulation / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics* / Q000503:physiopathology; D018895:Microsatellite Repeats; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
keywords: Alzheimer’s disease; Lewy Bodies; amyotrophic lateral sclerosis; mitochondrial metabolism; structural variants