Scientists use Affymetrix custom microarray to advance malarial study

Affymetrix, Inc. (NASDAQ: AFFX) announced today that an international team of researchers led by scientists at Boston College, the Broad Institute, and Imperial College London used an Affymetrix custom microarray to advance the study of malaria by assessing the variation in genetic structure and detecting known and novel genetic differences among malaria vector mosquito populations. This study will enable association studies that link mosquito genes to insecticide resistance and parasite infection susceptibility, ultimately helping to reduce malaria transmission.

“We plan to make this powerful array available to the community”

Published today in the journal Science, this groundbreaking discovery by a global consortium of 17 scientists, will enable more research on effective interventions against malaria, which annually sickens more than 240 million people and causes 860,000 deaths, most among young children. While advances in insecticides and anti-malarials have reduced transmission and death rates, the rate of decline is in danger of slowing due to increasing resistance to interventions, the mosquito's adaptive nature, and the pathogen's ability to evade mosquito defenses.

"The renewed goal among malaria researchers, advocated by Melinda Gates of the Gates Foundation in 2007, is to eradicate malaria in our lifetime," said lead researcher Marc Muskavitch, DeLuca Professor of Biology at Boston College. "But vaccines have not been successful, and insecticides and anti-malarials keep losing effectiveness. If we are going to eradicate it, new interventions are needed," he added. "What we needed was a better tool to look at the complexity of mosquito populations, to help us find genes that help mosquitoes evade our interventions and transmit disease."

The team used the Anopheles gambiae (AG) SNP1 Array, a proprietary microarray designed by Affymetrix in collaboration with the research team. The array features 400,000 SNPs of the 3 million found among four sequenced strains of Anopheles gambiae, providing vastly higher resolution than the 42- and 1,536-marker sets otherwise available to malaria vector biologists.

Over several malaria seasons, the international consortium, including scientists from the University of Notre Dame, the Malaria Research and Training Center in Mali, and the Harvard School of Public Health, collected mosquito samples from Mali and Burkina Faso and used the Affymetrix platform to genotype samples to validate array probes and define a vastly expanded SNP marker set for this malaria vector mosquito.

"With a higher resolution than ever before, we are beginning to understand how malaria vector mosquito populations become separated reproductively, in a process called 'incipient speciation,' and develop different traits to become better at evading interventions we deploy against them," noted Muskavitch. "Now we are developing new collaborations to use this tool to understand the genes underlying resistance to insecticides and the ability of mosquitoes to transmit malaria. Understanding those genes can help us to control mosquito populations more effectively, and try to help the mosquito use its defenses more effectively to reduce malaria parasite transmission."

"This groundbreaking research put scientists in the malaria community a step closer to identifying mosquito genes and alleles linked to malaria transmission, insecticide resistance, and parasite vulnerability," said Affymetrix President and CEO Kevin King. "Thanks to their work, the prospect of significantly reducing the spread of this disease and improving the lives of millions of people around the globe is within reach."

The scientists plan to encourage adoption of the AG SNP1 Array within the vector biology community in preparation for the next wave of research, which will focus on understanding the complexity of the mosquito populations in even greater depth, the mosquito genes that affect Plasmodium transmission, and the genes that can be used to improve mosquito control.

"We plan to make this powerful array available to the community," said Muskavitch. "We're expecting to complete this effort by early next year, when Affymetrix will make it available."

"As part of our ongoing focus on enabling genomic research in a wide range of species and disease and infectious areas, we are pleased to partner with Drs. Muskavitch of Boston College, Roger Wiegand of the Broad Institute, and their entire team to make this valuable research tool broadly available to the scientific community," said Jay Kaufman, Vice President of Strategic Marketing, DNA Applications, at Affymetrix. "With our long history of these partnerships, we recognize the value of cutting-edge scientific research combined with proven microarray technologies, and the overall benefit this brings to those pursuing the improvement of human health."

Another Affymetrix custom array is helping scientists looking to develop more effective treatments for malaria. The GNF Malaria Tiling Array, a high density tiling array of Plasmodium falciparum, developed in collaboration with the Genomics Institute of the Novartis Research Foundation, was used by an international team of scientists responding to increased tolerance to a new class of anti-malarials. Led by genomic scientist Elizabeth Winzeler of the Department of Cell Biology at the Scripps Research Institute, the team used the array to screen a diverse chemical library for new parasite-killing compounds and discovered a parasite gene that mediates resistance to a new potential drug lead. "Affymetrix microarray technology allowed us to rapidly examine the entire genome of the resistant malaria parasite strains and discover newly evolved mutations in PfATP4 that may be involved in maintaining ion homeostasis," said Winzeler. "Microarrays allowed us to simultaneously identify both the single-base changes and the copy number variants in PfATP4. It is not clear that we would have been as successful if we had used full-genome sequencing instead."

Source: Affymetrix, Inc.