Do you carry a rare DNA sequence missing from the human genome reference map?

Researchers have discovered 2,363 new DNA sequences corresponding to 730 regions on the human genome by using new approaches. These sequences represent segments of the genome that were not charted in the reference map of the human genome.

"A large portion of those sequences are either missing, fragmented or misaligned when compared to results from next-generation sequencing genome assemblies on the same samples," said Dr. Evan Eichler, senior author on the findings published April 19 in the advanced online edition of Nature Methods. Eichler is a University of Washington (UW) professor of genome sciences and an investigator with the Howard Hughes Medical Institute. "These findings suggest that new genome assemblies based solely on next-generation sequencing might miss many of these sites."

Dr. Jeffrey M. Kidd was lead author of the article, which described the new techniques the research team used to find some of the missing sequences.

Kidd headed the study while earning his Ph.D. at the University of Washington in the Eichler lab. Kidd is now a postdoctoral fellow at Stanford University.

"Over the past several years, the extent to which the structure of the genome varies among humans has become clearer. This variation suggested that there must be portions of the human genome where DNA sequences had yet to be discovered, annotated and characterized," he said "We hope that these sequences ultimately will be included as part of future releases of the reference human genome sequence."

The reference genome is a yardstick – or standard for comparison – for studies of human genetics.

The human reference genome was first created in 2001 and is updated every couple of years, Kidd explained. It's a mosaic of DNA sequences derived from several individuals. He went on to say that about 80 percent of the reference genome came from eight people. One of them actually accounts for more than 66 percent of the total.

Along with their collaborators at Agilent, the team designed ways to examine these newly identified sequences in a panel of people representing populations from around the world. The researchers found that, in some cases, the number of copies of these sequences varied from person to person.

The fact that a person can have one or more copies, or no copy at all, of a particular DNA sequence may account for why these sequences were missing from the reference genome. The researchers also found that some of these sequences were common or rare in different populations, depending on from which part of the globe their ancestors originated. ...

via New methods identify thousands of new DNA sequences missing from the human genome reference map.

The picture is continually unfolding to be more complicated than we originally imagined... but we are slowly making progress in understanding ourselves.

... Scientists at Duke University have created the first map of imprinted genes throughout the human genome, and they say a modern-day Rosetta stone -- a form of artificial intelligence called machine learning -- was the key to their success. The study revealed four times as many imprinted genes as had been previously identified.

In classic genetics, children inherit two copies of a gene, one from each parent, and both actively shape how the child develops. But in imprinting, one of those copies is turned off by molecular instructions coming from either the mother or the father. This process of "imprinting" information on a gene is believed to happen during the formation of an egg or sperm, and it means that a child will inherit only one working copy of that gene. That's why imprinted genes are so vulnerable to environmental pressures: If the only functioning copy is damaged or lost, there's no backup to jump in and help out.

Many of the newly-identified imprinted genes lie within genomic regions linked to the development of major diseases like cancer, diabetes, autism, and obesity. Researchers say that if some of these genes are later shown to be active in these disorders, they may offer clues to better disease prevention or management.

"Imprinted genes have always been something of a mystery, partly because they don't follow the conventional rules of inheritance," says Dr. Randy Jirtle, a genetics researcher in the departments of radiation oncology and pathology at Duke and a senior author of the study. "We're hoping this new roadmap will help us and others find more information about how these genes affect our health and well-being."...

via Science Daily