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International Team IDs Gene Expression Mediators in Moroccan Populations

NEW YORK (GenomeWeb News) – Both environmental and genetic factors contribute to white blood cell gene expression differences found between individuals in southern Morocco, according to a paper appearing in the early, online edition of Nature Genetics yesterday.

Researchers from the US, Australia, and Morocco used microarrays to look at expression patterns in leukocytes from around 200 Arab and Amazigh individuals in southern Morocco. They found that lifestyle — particularly whether individuals lived in a city or a rural village — played a larger role in the detected gene expression than either gender or ancestry. The team also identified hundreds of SNPs correlating with gene expression across the group.

"[A]s much as half of the transcriptome is influenced by the environment in a highly coordinated manner such that where a person lives explains up to a quarter of the variation for a substantial fraction of the transcripts," senior author Greg Gibson, a geneticist affiliated with North Carolina State University and the University of Queensland, and his co-authors wrote.

To explore the environmental and genetic factors affecting leukocyte gene expression, Gibson and his team collected blood samples from 284 individuals belonging to two self-reported ancestry groups: Amazigh Berbers, descended from the first modern humans to arrive in North Africa some 35,000 years ago, and Arabs, whose ancestors are thought to have arrived in Morocco in the seventh and eighth centuries.

The individuals tested came from urban communities near the Moroccan city Agadir and two rural villages, also in southern Morocco.

After using Illumina HumanHT12 bead arrays to assess the gene expression in leukocytes isolated from the blood samples and Illumina Human 610-Quad arrays to genotype them, the team tossed out samples that didn't meet their quality control specifications, leaving 194 samples for which gene expression and SNP data was available.

When they looked at factors affecting gene expression, the researchers found striking expression differences correlating with urban and rural location. For instance, they noted, small nucleolar RNA genes from the SNORD family seemed to be down regulated in individuals from the city but were more highly expressed in women from the village of Ighrem.

On the other hand, the team detected enhanced expression of ribosomal biosynthesis and oxidative phosphorylation related genes in about half of the individuals tested in Agadir, where the urban samples were collected.

The researchers also teased apart specific SNPs that are apparently tied to these expression differences, identifying 346 genes whose expression was influenced by SNPs in or around the affected gene and another ten genes affected by SNPs found elsewhere in the genome. Included were some SNPs previously identified in disease-association studies for conditions such as rheumatoid arthritis, type 1 diabetes, and lupus.

Still, because of the sample size, the researchers emphasized that these expression-related SNPs offer relatively little information about the transcriptional variation they observed overall — and even less insight into the genetic underpinnings of the environment-related expression differences detected.

"The robustness of the associations observed to the environmental effect raises the issue of whether genotype-by-environment interactions influence the peripheral blood transcriptome at all," the researchers wrote. "Although a few such interactions may exist, it would take a study comparing several thousand individuals from each location to reveal weaker genotype-by-environment interactions."

In the future, though, the researchers noted, a more refined understanding of the role of genes and environment in expression may be useful for informing the design and interpretation of genome-wide association studies aimed at finding disease-related genes.

"[G]ene expression profiling might be used to stratify individuals at higher risk for disease, thereby increasing the resolution of GWASs by focusing attention on the subset of individuals in whom genetic effects on disease are most pronounced," Gibson and his co-authors concluded.