Feature: Hidden in the genome

This feature appeared in the November/December 2010 issue of Australian Life Scientist. To subscribe to the magazine, go here.

What makes you you, and not someone else, are the millions of single-nucleotide polymorphisms (SNPs) residing in your genome. Together, these account for the majority of the genetic differences between any two people. And these variations affect not only an individual’s physical traits, but also their susceptibility to disease.

A genome wide association study (GWAS) seeks to characterise this variation across the genomes of a huge number of subjects and controls to identify associations of specific SNPs with a given disease. For geneticists, SNPs act as markers to locate genes in DNA sequences, thus implicating the ‘tagged’ genes in disease.

Since the first GWAS results were published in 2005, many risk and protective factors have been identified for dozens of common human conditions, including asthma, cancer, diabetes, heart disease and mental illness.

As new genetic information drives ever-more sophisticated products on the market to do GWAS and the trickle of data becomes a tsunami, some scientists and funding agencies are now starting to ask if pouring more mega dollars into these approaches will really deliver the extra ‘bang for their buck’.

Many of the GWAS findings are novel, with the ‘associated’ SNPs not previously implicated in disease. These results are especially exciting in light of the past difficulties replicating genetic findings for many diseases using linkage and candidate gene studies.

Such discoveries are informing researchers about basic aspects of the disease pathogenesis as well as revealing new avenues to detect, treat and prevent the disease. Such variations can also affect an individual’s response to therapy. Thus, GWASes have been touted as one of the first steps on the golden path to personalised medicine.

In practical terms, a GWAS essentially compares all or most of the DNA from individuals across two study groups: people with and without a disease or trait. The extracted DNA is analysed on gene arrays or ‘chips’ that can read millions of sequences simultaneously.

This technology is advancing almost daily, with one of the leading genetics technologies companies, Illumina, set to release its Rolls Royce bead-chip array, the Omni5. This will analyse around five million markers per sample. The chip results are analysed using bioinformatic tools to identify SNPs in the sample that mark blocks of DNA variations, or haplotypes. GWASes are generally non-hypothesis-driven, which means that they are like a very high-tech genomic fishing expedition, with SNPs as the bait and disease-associated variations the catch.

• Share
  Share this article

  •  google+
  • facebookfacebook
  • slashdotslashdot
  • diggdigg
  • RedditReddit
  • stumbleuponstumbleupon
  • linkedinlinkedin
  • twittertwitter
• print
• email
• Bookmark