Copy Number Variants in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a devastating disease mainly afflicting elderly people, characterized by decreased cognition, loss of memory, and eventually death. Although risk and deterministic genes are known, major genetics research programs are underway to gain further insights into the inheritance of AD. In the last years, in particular, new developments in genome-wide scanning methodologies have enabled the association of a number of previously uncharacterized copy number variants (CNVs, gain or loss of DNA) in AD. Because of the exceedingly large number of studies performed, it has become difficult for geneticists as well as clinicians to systematically follow, evaluate, and interpret the growing number of (sometime conflicting) CNVs implicated in AD. In this review, after a brief introduction of this type of structural variation, and a description of available databases, computational analyses, and technologies involved, we provide a systematic review of all published data showing statistical and scientific significance of pathogenic CNVs and discuss the role they might play in AD.

Keywords: Alzheimer’s disease; comparative genomic hybridization; copy number variations; gene expression; genome; genome wide association studies; mutation.

Fig.1

Description of deletion and duplication. Deletion occurs when in the sample genome there is a loss of a DNA segment in comparison with a reference genome while duplication is caused by the repetition of DNA segments.

Fig.2

Description of CGH array. Patient DNA and control DNA are labeled with fluorescent dyes and applied to the microarray; they hybridize on the microarray; the microarray scanner measures fluorescent signal intensity; computer software analyzes the data and generates a plot.