The research – published in Genetics – used a new technique to determine whether patients with a genetic condition known as homocystinuria were likely to respond to vitamin B6 treatment. The technique, based on genotyping, determined variations and responses to vitamin treatment in the human cystathionine beta synthase gene which, when defective, causes the inherited metabolic disorder.
The researchers, led by Dr Jasper Rine of University of California, Berkeley, USA, then correlated specific gene mutations to the severity of the disease; ranging from perfectly healthy and functional to severe and untreatable.
"We may have the DNA sequence of the human genome, but we're still trying to figure out what it means," said Mark Johnston, Editor-in-Chief of the journal Genetics. "This study moves us a step closer toward better understanding the genetic variability among people.”
Although the current study focused only on homocystinuria, the teams said the principle of testing the effects of naturally occurring gene variations can be applied to other inherited disorders, such as neural tube defect, cleft palate, and blindness.
Johnston said knowledge such mutations could help physicians prescribe treatments – such as supplementation with vitamins – based on genotype rather than outward symptoms or trial and error.
"The era of personal genome sequences is upon us, but there is a growing gap between the ability to sequence human genomes and the ability to understand the significance of variation in genome sequences," said Rine.
“This study demonstrates one way to close the gap; the data separate gene variants into distinct classes, including a group amenable to dietary intervention."
To make their determination of what genetic variations could be ‘treatable’ with vitamin B6, the research team ‘swapped’ the cystathionine beta synthase gene of baker's yeast with the gene from humans. They then tested which variations were healthy, and analysed which were treatable or untreatable with vitamin supplementation.
As a result, the study also clarified the function of 84 DNA sequence variants in the gene. The team said this information will also help physicians more effectively treat patients based on their particular genotypes.
Rine added that the approach opens doors for future studies examining other human genes implicated in diseases, especially if those genes similarly cross over between humans and yeast.
Volume 190, Number 4, Pages 1309-1323, doi:10.1534/genetics.111.137471
“Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles”
Authors: J.A. Mayfield, M.W. Davies, D. Dimster-Denk, N. Pleskac, et al