Two Strategies to Identify Genes Underlying Complex Diseases

Abstract

Dissecting the genetic basis of complex diseases remains one of great challenges in human genetics, because these diseases have polygenic determinations and involve multiple gene-gene and gene-environmental interactions. Definite conclusions about finding genes underlying complex diseases need substantial evidence from three levels of gene function. The traditional strategy of gene identification is to determine putative susceptibility genes on the DNA level, and then to find related association between susceptibility genes and complex diseases on the RNA and protein levels. However, with rapid development of technologies of proteomics and microarrays, a new high-throughput strategy backward from protein to RNA and further to DNA becomes available for gene discovery. This strategy can systemically test gene expression, analyze co-expressed genes or regulatory network, and detect the effects of environmental factors on the onset and development of complex diseases. Here we attempt to outline these two strategies using obesity as an example of a complex disease, and to compare their advantages and disadvantages. In conclusion, we suggest that these two strategies may complement each other and thus help to uncover a more comprehensively and more completely multifaceted spectrum of genetic determination for complex diseases.

Genetics of age at menarche: a systematic review

“…Candidate QTL can be determined at each of these levels by using the respective methods: association and linkage, at the DNA level; genome-wide gene expression microarrays, at the mRNA level; and proteomics, at the protein level. Identification of the QTL for menarcheal age may follow either forward (DNA RNA protein) or backward (protein RNA DNA) strategies but the latter looks more promising because it provides a possibility for systemic analysis of the gene expression, respective regulatory networks, and effect of genegene and gene-environment interactions on the onset of a complex trait (Lei et al, 2005). Ultimately, such a combined approach should open a new avenue in the efforts towards determining a genetic basis of menarche and its timing.…”