BETHESDA, MD -- April 9, 2012 -- Scientists have moved a step closer to correcting some unhealthy gene mutations with diet, according to a new research report appearing in the April 2012 issue of the journal GENETICS (http://www.genetics.org/). Researchers from the University of California, Berkeley, determined variations and responses to vitamin treatment in the human cystathionine beta synthase gene, which when defective, causes the disease homocystinuria, an inherited metabolic disorder sometimes treatable with vitamin B6. After the analysis, scientists correlated specific gene mutations with severity of the disease, ranging from perfectly healthy and functional to severe and untreatable. Although the current study focused on homocystinuria, testing the effects of naturally occurring gene variations using surrogate organism genetics can be applied to other inherited disorders, such as neural tube defect, cleft palate, and blindness.
"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 Jasper Rine, Ph.D., the principal investigator of this research in the Department of Molecular and Cell Biology at the California Institute of Quantitative Biosciences at the University of California, Berkeley. "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, scientists "swapped" the cystathionine beta synthase gene of baker's yeast with the gene from humans to test which variants were healthy, treatable, or untreatable with additional vitamin B6. As a result, the study clarified the function of 84 DNA sequence variants in this gene, which will help physicians more effectively treat patients based on their particular genotypes. In addition, this approach opens doors for future studies examining other human genes that similarly cross over between humans and yeast.
"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. More immediately, knowledge of these gene mutations will help physicians prescribe treatment based on genotype rather than outward symptoms or trial and error."
CITATION: Jacob A. Mayfield, Meara W. Davies, Dago Dimster-Denk, Nick Pleskac, Sean McCarthy, Elizabeth A. Boydston, Logan Fink, Xin Xin Lin, Ankur S. Narain, Michael Meighan, and Jasper Rine.
Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles
Genetics April 2012 190:1309-1323
ABOUT GENETICS: Since 1916, GENETICS (http://www.genetics.org) has covered high quality, original research on a range of topics bearing on inheritance, including population and evolutionary genetics, complex traits, developmental and behavioral genetics, cellular genetics, gene expression, genome integrity and transmission, and genome and systems biology. GENETICS, the peer-reviewed, peer-edited journal of the Genetics Society of America is one of the world's most cited journals in genetics and heredity.
ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. The GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes GENETICS, a leading journal in the field and a new online, open-access publication, G3: Genes|Genomes|Genetics. For more information about GSA, please visit www.genetics-gsa.org. Also follow GSA on Facebook at facebook.com/GeneticsGSA and on Twitter @GeneticsGSA.