DNA's 'Rungs' May Be What Makes Us Different

All parents must wonder from time to time why their children, produced by the same gene pool, can be so different from each other. Often even siblings who look the same and are raised in essentially the same environment can be like night and day, opposites in so many ways.

How can that be? Why are we all unique?

Scientists at three institutions have pooled their resources and come up with a surprising clue. Even the collection of genes we inherit from our parents, while nearly identical for all members of the human family, are structured quite differently than we have been told over the last few decades.

"One of the interesting observations that has come out of the human genome project over the last five years or so is the broad sweeping statement that if you compare the DNA in any two genomes in the population they are 99.9 percent identical," says geneticist Stephen Scherer of The Hospital for Sick Children in Toronto, one of the lead authors of a major study published in the September issue of the journal Nature Genetics.

"So my genome and Bill Clinton's are 99.9 percent identical," Scherer says with a chuckle. DNA, which consists of two strands of chemical compounds, called nucleotides, linked together to form a ladder that has been twisted into the shape of a winding staircase, carries the individual blueprint for every creature on the planet. All humans share 99.9 percent of the same nucleotides, a remarkable number that makes it hard to figure out why we are all very distinct individuals.

"It means we all have a common heritage, and it sounds like we are nearly identical, but if you think about the size of the genome, you inherit 3 billion pairs of nucleotides, or chemical bases of genetic information, from your mom and your dad. So even 0.1 percent difference is still 3 million chemical base changes, so that's a lot."

And it is that 3 million different sources of genetic information that make us each different, scientists have argued.

"That's what we believed," Scherer says. "That's what I taught my students."

Missing Rungs

But that's probably going to change now. Scherer says he was "astonished" when early results of a research project at his hospital began coming in. He soon learned of similar results at other studies underway at Harvard Medical School and Brigham and Women's Hospital, and researchers at all three institutions decided to pool their resources.

What came out of all of that is research that could reshape our understanding of why each of us is different, and why some of us may be more prone to certain diseases than others. The difference, the researchers say, is not just in the number of small changes in the tiny points on both sides of that twisted ladder where genetic information is stored. The difference is in the numbers.

It's sort of like some ladders having more rungs, and others fewer.

DNA continually replicates, or copies, itself so that each descendent cell carries the same genetic information down the line, and it had been thought that the process of replication was essentially the same for all normal individuals. It is that assumption that the new research challenges.

"When we first made the observation we thought, wow, there's people walking around who are apparently healthy who are missing half a million nucleotides on one chromosome or in some cases gained half a million and it doesn't seem to affect them," Scherer says.

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