Genomic sister-disorders of neurodevelopment: an evolutionary approach

B Crespi, K Summers, Stephen Dorus

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Genomic sister-disorders are defined here as diseases mediated by duplications versus deletions of the same region. Such disorders can provide unique information concerning the genomic underpinnings of human neurodevelopment because effects of diametric variation in gene copy number on cognitive and behavioral phenotypes can be inferred. We describe evidence from the literature on deletions versus duplications for the regions underlying the best-known human neurogenetic sister-disorders, including Williams syndrome, Velocardiofacial syndrome, and Smith-Magenis syndrome, as well as the X-chromosomal conditions Klinefelter and Turner syndromes. These data suggest that diametric copy-number alterations can, like diametric alterations to imprinted genes, generate contrasting phenotypes associated with autistic-spectrum and psychotic-spectrum conditions. Genomically based perturbations to the development of the human social brain are thus apparently mediated to a notable degree by effects of variation in gene copy number. We also conducted the first analyses of positive selection for genes in the regions affected by these disorders. We found evidence consistent with adaptive evolution of protein-coding genes, or selective sweeps, for three of the four sets of sister-syndromes analyzed. These studies of selection facilitate identification of candidate genes for the phenotypes observed and lend a novel evolutionary dimension to the analysis of human cognitive architecture and neurogenetic disorders.
Original languageEnglish
Pages (from-to)81-100
Number of pages20
JournalEvolutionary Applications
Volume2
Issue number1
DOIs
Publication statusPublished - 2009

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neurodevelopment
genomics
Gene Dosage
Phenotype
gene dosage
gene
Smith-Magenis Syndrome
phenotype
Williams Syndrome
DiGeorge Syndrome
Klinefelter Syndrome
Turner Syndrome
genes
Genetic Association Studies
Human Development
Genes
human development
Brain
brain
Proteins

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Genomic sister-disorders of neurodevelopment: an evolutionary approach. / Crespi, B; Summers, K; Dorus, Stephen.

In: Evolutionary Applications, Vol. 2, No. 1, 2009, p. 81-100.

Research output: Contribution to journalArticle

Crespi, B ; Summers, K ; Dorus, Stephen. / Genomic sister-disorders of neurodevelopment: an evolutionary approach. In: Evolutionary Applications. 2009 ; Vol. 2, No. 1. pp. 81-100.
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