Aneuploidy: an important model system to understand salient aspects of functional genomics.

Abstract

Maintaining a balance in gene dosage and protein activity is essential to sustain normal cellular functions. Males and females have a wide range of genetic as well as epigenetic differences, where X-linked gene dosage is an essential regulatory factor. Basic understanding of gene dosage maintenance has emerged from the studies carried out using mouse models with FCG (four core genotype) and chromosomal aneuploidy as well as from mono-chromosomal hybrid cells. In mammals, aneuploidy often leads to embryonic lethality particularly in early development with major developmental and structural abnormalities. Thus, in-depth analysis of the causes and consequences of gene dosage alterations is needed to unravel its effects on basic cellular and developmental functions as well as in understanding its medical implications. Cells isolated from individuals with naturally occurring chromosomal aneuploidy can be considered as true representatives, as these cells have stable chromosomal alterations/gene dosage imbalance, which have occurred by modulation of the basic molecular machinery. Therefore, innovative use of these natural aneuploidy cells/organisms with recent molecular and high-throughput techniques will provide an understanding of the basic mechanisms involved in gene dosage balance and the related consequences for functional genomics.