Scientists find antibody genes not universal

Vancouver, BC – Drugs and vaccinations that are designed to treat entire populations may be missing their mark, according to a new study from a team of North American scientists, including lead researcher Felix Breden, professor and departmental chair of Simon Fraser University’s Department of Biological Research.

They have discovered that many of our antibody genes, which fight off infection, operate differently from person to person, and that ethnicity may also play a role in how they fight off infection.

This means that even though drugs, treatments and vaccinations are designed to treat entire populations, our response to them could be individualistic.

The scientists made these discoveries after completely sequencing the immensely repetitive DNA in the human genome’s one million nucleotide-long immunoglobulin heavy (IGH)-chain locus.

Scientists have long known that our IGH-chain locus is our most prolific producer of the diverse, 50-plus antibody-encoding genes that our B cells use to fight off infections and diseases. But thanks to new data-mining technology, this is the first study to radically refine what has been a haphazard genomic map of the human IGH-chain locus.

“Because this is the most complete version of a human’s IGH sequence, we have basically given this part of our genome a data facelift, and the sequences we generated are now being integrated into the official human genome project assembly,” says Corey Watson, a postdoctoral researcher at the Mount Sinai School of Medicine in New York. Watson completed his doctoral studies under Dr Breden’s supervision, and the two scientists still collaborate on research.

Using a single chromosome of an individual, the latest study sequences all possible antibody-encoding genes in our IGH-chain locus. It also identifies 11 possible large DNA insertions and deletions of antibody-encoding genes in the region that determine our antibody gene count/diversity and, in some cases, our susceptibility to disease.

The scientists uncovered the link between antibody makeup and ethnicity when they screened the chromosomes of 425 people of Asian, African and European descent for several DNA insertions and deletions.

“It is early days, but these findings could mean that past environmental exposures to certain pathogens are associated with increased prevalence of DNA insertions or deletions in different ethnic groups, which could impact disease risk,” says Watson. “Most important for current studies of antibody genetics and disease is that our results demonstrate that researchers need to take into account the ethnicity of DNA samples used.

”This study’s findings will advance research on how IGH-related antibodies’ genetic variation between individuals impacts our ability to fight viruses such as the flu and HIV.

Watson, Breden, three other SFU scientists (Jamie Scott, Jeffery Joy and Robert Holt), science alumnus Jeremy Willsey and researchers in the United States and at the BC Cancer Agency contributed equally to this study.

Evan Eichler, a scientist at Seattle’s University of Washington genome sciences department and Howard Hughes Medical Institute, developed the technology making the study possible.

The American Journal of Human Genetics (Cell Press) published its findings in the article Complete Haplotype Sequence of the Human Immunoglobulin Heavy-Chain Variable, Diversity and Joining Genes and Characterization of the Allelic and Copy-Number Variation, in its March 28 issue.