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Comparative Genomics: Unraveling the Genetics of Human Disease
CHORI Welcomes New Principal Investigator to the Center for Genetics

CHORI is pleased to welcome Dario Boffelli, PhD, who has just joined CHORI’s Center for Genetics from the Lawrence Berkeley National Laboratory, Genomics Division. Dr. Boffelli, whose area of interest is in comparative genomics, will add to the internationally renowned center dedicated to the elucidation of the genetics underlying human disease.

“You can learn so many things by comparing the sequences of genomes from different species,” explains Dr. Boffelli. “In general, the genomic sequences that are similar across two different species are highly likely to be functionally important, as they have been retained over many years of independent species’ evolution.”

These similar genetic sequences, or areas of conservation, have emerged within the last decade as a powerful tool in the effort to identify from the billions of bases that make up a species’ DNA which 2 to 10 percent encodes genes or regulatory information.

“The human genome, for example, is about three billion bases long, while it’s estimated that only two or three percent of the genome contains genes, and only three to four percent contains sequences that control gene expression,” says Dr. Boffelli. “This means that at best only ten percent of the genome codes for function, and the remaining ninety percent doesn’t really do anything at all.”

Within the larger area of comparative genomics, Dr. Boffelli has two major research foci which he will be exploring at CHORI. The first, utilizing a strategy Dr. Boffelli was instrumental in developing, is to compare genomes between multiple primate species and the human genome as a tool to identify those sequences that are conserved in humans due to selective pressure rather than evolutionary type. This kind of specialized analysis successfully identifies regulatory sequences not otherwise detectable (Genome Biology, 2007).

“The second area is to use comparative genomics to help with the interpretation of genetic studies of human disease,” says Dr. Boffelli.

While there has been remarkable success in identifying those sequences that underlie the genetic basis of very rare and severe genetic disorders such as sickle cell disease or cystic fibrosis, there has been much more limited success in finding the genetic basis for more common diseases, such as heart disease, cancer or diabetes.

“This is because many of the sequence changes in the human genome that under common disease may not be found in protein sequences, which we understand very well, but in regulatory regions, which are much more difficult to determine,” Dr. Boffelli explains.

Comparative genomics offers potential solutions to the problem, however, by looking at whether sequence changes in the human genome have been conserved across primate species and making predictions about their functional importance. Making such predictions, however, requires interface with a clinical population, however, one of the main reasons Dr. Boffelli came to CHORI.

“Clinicians provide the patient populations and I provide predictions of which sequence variations might be more functionally relevant,” Dr. Boffelli explains. “We try to find out of my predictions can contribute to explaining part of the genetics of the disease.”

With CHORI’s unique ability to provide cross-disciplinary research between basic and clinical science, the institute was an ideal choice for Dr. Boffelli to continue to explore this relatively new research approach.

“We had no easy connection to the clinical side of life,” says Dr. Boffelli of his previous position.

“Here at CHORI, there is the great potential for interaction with clinically focused investigators who want to combine genomic approaches to disease investigations.”

With the latest addition of Dr. Boffelli’s fresh insights and investigatory rigor, CHORI’s Center for Genetics will continue to bridge the gap from bench to bedside in the search for the genetic underpinnings of common human diseases.


Thursday, September 4, 2014 6:02 PM

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