Over the next year, scientists expect to uncover genetic secrets of such complex diseases as diabetes, heart disease, and autism. Studies of these diseases using powerful new gene chips, which can quickly identify a genetic sequence linked to risk of a particular disease, are now under way. The results could lead to new diagnostics, drug targets, and understanding of these complex diseases.

One of the makers of these new gene chips, San Diego-based Illumina, is now looking ahead to the next phase of medical genetics. The company has recently acquired new diagnostic and sequencing technologies, which it plans to use to better identify medically relevant genes. Ultimately, the goal is to diagnose risk of specific diseases and identify the best treatment options for certain patients.

The Illumina chip contains 650,000 short sequences of DNA that can identify SNPs (single nucleotide polymorphisms), carefully selected from a map of human genetic variation known as the HapMap (see “A New Map for Health”). Each SNP represents a spot of the genome that frequently varies among individuals and acts as a signpost for that genomic region. Scientists use the chip to search for genetic variants that are more common in a group of people with the disease of interest. David Barker, vice president and chief scientific officer at Illumina, talked with Technology Review about the company’s plans.

Technology Review: Tell me about the Illumina chip.

David Barker: The [DNA sequences] on the chip were chosen to represent the common variation in the genome mapped in the HapMap. The microarray does a good job of capturing all that variation and can help discover genes that control risk of major diseases, such as cancer, asthma, diabetes, and heart disease.

TR: What kinds of projects are under way?

DB: We are working with an Icelandic company, DeCode, which will genotype half the population of Iceland and will look for associations in all kinds of diseases (see “Genomics into Drugs”).

Lots of other projects are in progress. Children’s Hospital of Philadelphia, for example, plans to type every patient who walks in the door, as well as their parents. They aim to have 30,000 samples by the end of the year and will look for associations with different childhood diseases.

Some studies are already bearing results, even though the chip has been out for less than a year. A paper published earlier this month in Science identified a gene with a strong association with inflammatory bowel syndrome, or IBS, which includes Crohn’s disease and colitis. People with IBS have an autoimmune reaction that damages their own tissue. The researchers identified a rare variant of a gene for a protein released during inflammation that actually provides protection against the disease. The findings provide new targets for drugs to treat the condition.

TR: Illumina added more SNPs to its newest chip, selected primarily from the African population. Why is this important?

DB: African Americans are more susceptible than Caucasians to some diseases, such as cardiovascular disease and Type 2 diabetes. To find the genetic variations responsible, we need to take into account the greater genetic diversity of the African population.

We had a chip with 550K [500,000] SNPs on an array, but that was not enough to capture the genetic variation in the African population. This population has high genetic variation because they have not gone through the evolutionary bottlenecks of other populations, such as emigrating from Africa or surviving the ice ages in Europe. So we added 100,000 SNPs from the Yoruba population [a West African population studied in the HapMap], which will be useful for studying the African-American population.

TR: Illumina recently acquired a gene-sequencing company, Solexa. Why?

DB: Once you find an SNP that is associated with a disease, you often need to sequence that region of the genome to find the causative variation. That means a lot of resequencing of specific parts of the genome. So we want to provide our customers with sequencing capabilities, and we think Solexa has the best technology.

TR: What else is in the works at Illumina?

DB: Our new product is iSelect, which allows people to design a chip with up to 60,000 SNPs of their own choosing. Such a chip could be used to diagnose a disease [in humans] or to study genes in other animals. For example, we have developed a bovine chip (see “Gene Chips for Cows”).

TR: How would such chips work for diagnostics?

DB: We would need to narrow down the number of SNPs associated with a particular disease. Ultimately, the chips could be used to diagnose the disease and potentially to identify the best treatment for an individual. We’re currently collaborating with DeCode, which has discovered SNPs associated with cardiovascular disease. We’ll develop an assay for six to eight of those SNPs.