A nationwide consortium led by the UW has completed the first sequence-based map of structural variations in the human genome, giving scientists an overall picture of the large-scale differences in DNA between individuals.
The project gives researchers a guide for further research into these structural differences, which are believed to play an important role in human health and disease. The results appear in the May 1 issue of the journal Nature.
The project involved sequencing the genomes of eight people from a diverse set of ethnic backgrounds: four individuals of African descent, two of Asian descent, and two of European background.
The researchers created what’s called a clone map, taking multiple copies of each of the eight genomes and breaking them into numerous segments of about 40,000 base pairs, which they then fit back together based on the human reference genome. They searched for structural differences that ranged in size from a few thousand to a few million base pairs. Base pairs are one of the basic units of information on the human genome.
Most previous studies of the genome have focused on small genetic variations called single-nucleotide polymorphisms – changes on the scale of a single base pair.
More recent research on the human genome has shown, however, that larger-scale differences may account for a great deal of genetic variation among individuals. Structural variation in the human genome has already been linked to individual differences in susceptibility to conditions like coronary heart disease, HIV, schizophrenia, autism, and mental retardation.
In addition to millions of smaller differences, the researchers identified 1,695 regions of structural variation in the genome. They also provided a detailed look at the sequence for 261 regions of the genome, revealing an unprecedented view of the complexity of the genetic differences among different humans.
The large-scale differences that the researchers were looking for can come in many forms, such as the deletion of a large swath of DNA, or the insertion of an out-of-place string of genetic code. Others simply appear as a different number of copies of a gene or DNA sequence.
Until now, there has not been a comprehensive study to sequence these variations systematically in multiple individuals. As part of their study, the authors also discovered 525 segments of DNA that were previously unknown to the human genetics community.
The project can serve as a sound resource for the science community, the researchers said, since they have preserved the many segments of DNA used for the project. As new genomes are studied, someone might find a new sequence or new area of variation, and the researchers can revisit that particular segment of DNA to study it more closely.
The project was led by Evan Eichler, UW associate professor of genome sciences and an investigator for the Howard Hughes Medical Institute.
In addition to Eichler, several UW researchers in the UW Departments of Genome Sciences and Medicine were involved, including Jeffrey Kidd, a graduate student in genome sciences, and Maynard Olson, professor of medicine and genome sciences and director of the UW Genome Center.