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An alternative to whole-genome sequencing
SHENZHEN, China—With a common interest in developing new approaches to studying the Major Histocompatibility Complex (MHC) region—a large cluster of genes that plays a critical role in the development or progression of hundreds of diseases—Roche NimbleGen Inc. and BGI recently announced they have developed technology that can be used to study this region on genome-wide scale.
Found on the short arm of chromosome 6, MHC is a large cluster of genes that covers a 3.6Mb region including 150 expressing genes. MHC has been shown to play a critical role in many serious diseases such as cancer, AIDS, diabetes, arteriosclerosis and leukemia. Given its integral function in the regulation of immune system, MHC has become a key target in drug research and development for a number of diseases.
According to BGI, MHC shows a high degree of polymorphism that complicates the studies of genes in this region, and its gene density (37 per Mb) is five times higher than the average gene density of the whole genome (7 per Mb). Because of its polymorphic nature, linkage disequilibrium and inheritance of haplotype, MHC has been targeted for a wide range of research applications, including population evolution, paternity testing, HLA typing and organ transplant matching.
The MHC region capture technology developed by Roche and BGI is an efficient strategy to study the whole MHC region by selectively enriching this region using an oligo hybridization approach, says BGI. The technology not only targets the traditional MHC region (3.37MB), it also targets approximately 1.6Mb of the regions surrounding MHC, providing a total of 4.97Mb (chr6: 28477797-33448354) and includes eight known haplotypes.
The technology is a faster and more cost-effective approach than whole-genome sequencing, explains Jiang Hui, associate director of science and technology at BGI. Compared to existing genotyping technologies, the new technology enables targeted sequencing of 97 percent or more of the overall MHC region, and close to 100-percent coverage of the gene coding regions, says Hui.
"The high accuracy of this new technology is demonstrated by a 99.42-percent concordance with traditional genotyping technologies," Hui adds. "But not only does this technology enable accurate genotyping of known SNPs, it provides the opportunity to discover novel SNPs."
Discovering novel SNPs is important to furthering genotyping research because "those novel SNPs may exist with a very low, minor allele frequency, or arise by novel mutation, and may be related with some rare diseases," says Hui. "By genotyping, we can only get the SNP information that is already known because the genotyping array is designed according to the dbSNP or 1000 Genomes project."
In their partnership, China-based BGI was responsible for sequencing and developing the bioinformatic analysis pipeline, while Roche was in charge of the probe design and capture reagents production.
"In autoimmunity diseases or other complex diseases that are related to the immune system, we could discover the disease-related genes by analyzing large cohort of control versus case samples with this technology," Hui says. "Investigating the function and signal pathway of those genes can help drug research."
Roche did not respond to requests for comment.