NeuroTalk Support Groups - Linking Disease to Gene Variations

Jan 1 2009 (Vol. 29, No. 1)

Feature Article
Linking Disease to Gene Variations
Predisposition Based on Genomics Is Slowly Being Ascertained
Vicki Glaser

Each human chromosome has dozens to hundreds of millions of base pairs of DNA, and variants in those base pairs can be associated with disease. New technologies and strategies for genetic testing and genomic analysis were the focus of several presentations at the recent American Society of Human Genetics (ASHG) meeting in Philadelphia. Understanding the molecular basis of disease, discerning inheritance patterns of genetic disorders, and clarifying the implications of predisposing genetic factors are core goals of genome-wide association studies (GWAS).

As researchers and clinicians continue to unravel the mysteries of the human genome, they are looking to technology companies to provide next-generation sequencing and genome analysis tools to accelerate whole-genome and targeted DNA sequencing, SNP genotyping, and copy-number variation (CNV) analysis.

Aravinda Chakravarti, Ph.D., ASHG president and professor at the McKusik-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, defined the challenges that must be overcome before the inevitable future of personalized medicine can become reality. “This reality cannot become routine or useful unless we can predict the phenotype of each of our unique genomes within which the vast majority of variation is rare and unique.

“First, we need to understand the origin of variation. To gain an unbiased functional understanding we need to quantify the human mutation rate directly and how it is modulated. Second, progress in prediction will require not merely accumulating empirical facts but theoretical prediction of the functional content of any piece of DNA and the consequences of altering that sequence.”

To achieve this, the field needs to be able to assess many more genomes, to integrate structural variation with mutation/SNP data, and to evaluate variation in noncoding regions of the genome. The hope is that next-generation sequencing technology will allow for sequencing of more genomes with greater coverage and for targeted resequencing to enable detection of rare disease-associated alleles such as small insertions, deletions, or inversions.
http://www.genengnews.com/articles/c...id=2714&chid=4