NEW YORK (GenomeWeb News) – In a study appearing online today in BMC Genomics, researchers from the University of California at San Francisco and GlaxoSmithKline's Research Triangle Park have started mapping copy number variants in the genomes of healthy African Americans. The team used microarrays to look for CNVs in the genomes of 385 African Americans from dozens of states.
Lead author Joseph McElroy, a post-doctoral researcher at UCSF, told GenomeWeb Daily News that the work represents a first step in characterizing CNVs in a healthy African American population. He and his colleagues hope that establishing such a baseline will assist them in their search for genetic changes associated with multiple sclerosis in African Americans — research they are currently undertaking.
"We have now a basic map of CNVs in the African American population — in the [healthy] controls," McElroy said.
CNVs, which result from deletions or duplications in the genome, have been implicated in everything from rare genetic conditions to complex traits and diseases. Previous studies have turned up thousands of CNVs in the human genome, ranging in size from a thousand to millions of bases of DNA.
"Copy number variants have been identified in several studies to be associated with complex diseases," McElroy and his co-authors wrote. "It is important, therefore, to understand the distribution of CNVs within and among populations."
But, the authors noted, despite international efforts to understand CNVs in human populations as a whole, little to no research has been directed towards understanding the normal range of CNVs specifically in African Americans.
In an effort to document the normal range of CNVs in this population, the researchers used an Affymetrix GeneChip Human Mapping 500K Array Set to look for CNVs in genomic DNA from 435 African Americans from 28 states. For 140 samples, DNA was isolated from female lymphoblastoid cell lines. DNA for the remaining samples came from whole blood samples.
From this group, the team used 50 African American women to form a reference group for the study, comparing them with the other 385 individuals. While McElroy said the chip they used "did a pretty good job of detecting CNVs," he noted that it probably didn't detect all of them. He said the team is currently using newer arrays that are believed to detect more CNVs in the human genome.
Overall, the researchers detected 1,362 CNVs in the African American individuals tested. Most — but not all — of these are also housed in the Database of Genomic Variants. Many were low frequency CNVs, McElroy noted, with relatively few peaks of common CNVs.
Meanwhile, the team turned up 1,972 CNVs in the genomes of 435 individuals of European descent from Australia, eastern Europe, North Africa, North America, northern Europe, South America, southern Europe, and western Europe.
For the most part, McElroy said, the difference in the overall number of CNVs in each population likely reflects the fact that researchers used the same 50 African American women as a reference population for both the African American group and the European-descent group.
Just two spots in the genome housed significantly different CNV frequencies between the two populations: a stretch of DNA on chromosome 17 that was duplicated in about 45 percent of the individuals of European descent but just eight percent of African Americans and a region on chromosome 15 that was duplicated in around 40 percent of European-descended individuals and about 21 percent of African Americans.
The team is now doing research aimed at identifying genotypic and CNV changes linked to multiple sclerosis in African Americans, looking at roughly 700 African Americans with MS and about 600 healthy controls, McElroy said. Their current study of CNVs should help them discern real MS-related genetic changes from healthy genetic variation, he explained.
"The generation of the CNV map will be a valuable tool for identifying disease associated CNVs in African Americans," McElroy and his co-authors wrote.