HUGO: The disease-gene link

Biplab Das

doi:10.1038/nindia.2008.286 Published online 26 September 2008

The Human Genome Project (HGP) is to deciphering our genetic blueprint what Apollo is to unraveling secrets of the moon. Since its results came to light, HGP has unlocked the secrets of diseases linking them to defective genes. Geneticists across the globe have been compiling enormous amount of data on how culprit genes underlie various diseases. The challenge in the post-genomic era, however, has been to get insights into disease-related genes.

An international symposium on 'Complex Diseases: Approaches to Gene Identification and Therapeutic Management' saw global experts unraveling valuable data on prevalence of diseases and the genes associated with them.

(From left) Edison Liu, Nitai Bhattacharyya & Raj Ramesar at the meet.

At a satellite meeting of the Human Genome Organisation (HUGO), in its 20th year of existence, Raj Ramesar of the Univesity of Cape Town and Allied Hospitals, South Africa reported the South African disease-genes link. "There is a strong prevalence of colorectal cancer in small pockets of South Africa," he said at the meet jointly organized by the Indian Statistical Institute, Saha Institute of Nuclear Physics and Indian Institute of Chemical Biology in Kolkata on September 25 and 26. The meet was part of the Human Genome Meeting to be held at Hyderabad from September 27 to 30.

On the enormous growth of the repository on colorectal cancer (CRC) DNA, Ramesar said, "The repository has grown considerably since its inception, and now contains DNA, research and clinical data on 1525 individuals in 400 families." The emphasis, he said, was on identifying individuals carrying mutations in the DNA mismatch repair genes that cause hereditary non-polypotic colorectal cancer (HNPCC).

Exciting new work on the origin of a certain mutation (C1528T) on a certain gene (hMLH1) that causes CRC in the South African population has revealed that the mutation dates back to about 450 years ago, Ramesar said. This information will be extremely important in reconsidering the screening regimen for mutation carriers.

"We have also homed in on defects in gene that code for carbonic anhydrase IV (CAIV), a defect that causes controlled cell death in the eye," he reported.

The role of environment cannot be undermined in disease causation, he said. "We have to obtain information down to the level of single base pair and how it interacts with environment to produce external traits (phenotypes)," Ramesar added.

Geneticists have also started scanning whole human genome to look for disease related genes. John Blangero of Southwest Foundation for Biomedical Research, San Antonio, Texas, US said, "We selected symptoms like blood pressure, obesity, diabetes, inflammation, oxidative stress and hormonal disorders and launched a genome wide scan."

"…Now, we have data on 550,000 single nucleotide polymorphisms (SNPs), a change in single base in DNA," Blangero said. To track these SNPs, which have been shown to have a growing role in disease prevalence, Blangero and his teammates use a system comprising 3000 processors, which will be upgraded in near future to harbour 100,000 processors to sequence the whole genome.

Elaborating on the underlying genetic story of HIV infection and AIDS, which has already claimed 25 million lives, Sunil K. Ahuja of University of Texas Health Science Center, San Antonio, said a particular genetic mutation makes people susceptible to HIV-AIDS. "We have assessed the risk of AIDS based on CC chemokine receptor 5 (CCR5) and the gene copy number of CCL3L1, a potent HIV-suppressive chemokine." According to Ahuja, the higher the copy number of CCL3L1, the lower is the susceptibility of HIV-AIDS. Similarly, interesting new findings on the underlying genetic features of a single gene disease — Huntington's disease — were discussed by Nitai P. Bhattacharyya of Saha Institute of Nuclear Physics.

Edison Liu, president of HUGO and director of the Genome Institute of Singapore, said a tumour suppressing gene (p53) had huge implications in breast cancer as well as other forms of cancers. "We have identified more than 100 new target genes to which p53 binds. This could be of prognostic significance," Liu pointed out.