Genetic Heterogeneity and Human Diseases

The contribution of karyotype heterogeneity to human diseases is a crucial but overlooked issue. Recent genomic research has revealed high levels of genetic/epigenetic heterogeneity, in particular karyotypic heterogeneity and somatic mosaicism associated with many complex but common human diseases. These important findings challenge the current gene-based concept of many common diseases. To frame this new emerging field, this publication presents pertinent examples linking karyotype heterogeneity to diseases and identifying it in the general population. Specifically, a few key topics essential to understanding karyotypic heterogeneity are discussed, including genomic instability, nonclonal chromosome aberrations, previously unreported/ignored types of chromosome aberrations, cell death heterogeneity and somatic mosaicism. These subjects are discussed with an emphasis on determining the biological implications of genomic heterogeneity and synthesizing these implications into the frameworks of systems biology and genome theory.