60 new genes controlled by regulatory sequences

Researchers worldwide are seeking to define ancient sections of our genetic code that may soon be as important to medical science as genes.

A new wave of research is concerned with, not how genes work, but how small regulatory DNA sequences tell genes where, when and to what degree to "turn on." As part of this effort, researchers at the University of Rochester Medical Center scanned through the vast human DNA code to reveal for the first time 60 genes influenced by one such sequence, according to an article published in the journal Genome Research.

Growing knowledge of how regulatory sequences control gene behavior has the potential to create new classes of treatment for nerve disorders and heart failure.

Such sequences may also help to explain why humans are so complex, despite having one-fifth as much genetic material as wheat for instance. Medical center researchers are working on just one of more than 100 regulatory sequences identified so far, each the subject of intense study.

"Most people don't realize that genes make up a very small percentage of the human DNA code," said Joseph M. Miano, Ph.D., senior author of the journal paper and associate professor within the Cardiovascular Research Institute at the medical center. "Genes are relatively straightforward compared to what lies ahead. We believe that the real genetic gymnastics, the real intelligence of our system, is controlled by tiny bits of genetic material that tell genes what to do."

Genes are the chains of deoxyribonucleic acids (DNA) that encode instructions for the building of proteins, the workhorses that make up the body's organs and carry its signals. The Human Genome Project, which first reported results in 2001, produced a near complete listing of the DNA sequences that make up all human genes (the genome). Key project findings included that human genetic material consists of about 3 billion base pairs, the "letters" that make up the genetic code. Researchers also concluded that genes, specific batches of code that direct protein construction, comprise just about 2 percent of all human DNA. A central question in genetics has become: what does the remaining 98 percent of human genetic material do?

Regulatory sequences are emerging as an important part of the non-gene majority of human genetic material, once thought of as "junk DNA." A new frontier in genetic research is the defining of the regulome, the complete set of DNA sequences that regulate the behavior of genes. DNA segments that code for proteins average 200 base pairs in length, whereas regulatory sequences typically include just six to 10 base pairs, making them hard to find.

As a human embryo develops from a single cell into tens of billions of cells, DNA must be read and copied again and again to supply each cell with its needed copy. Over time, random changes, or mutations, are inserted into the code during the copying process. Some mutations bring survival advantages and others cause disease. Most known genetic diseases identified to date result from a mutation within a gene that directs protein construction, but that may soon change.