"I knew that I wanted to do genetics when I was in grade 9, and by grade 10 I knew that I wanted to do human genetics," says Eichler. He grew up on a farm in far northern Canada, where winter locks the landscape in icy splendor. His father grew wheat and canola in summer and taught French in a nearby town the rest of the year. His mother raised Angora rabbits, whose wool she would spin into yarn for sweaters. "My mother was one of those people who didn't like dyes, so she decided that she wanted a natural variation of colors," Eichler says. "She said to me, 'Can you figure out how to get these other colors, these creams and buffs and so on?' That's where I learned the basic genetic coat color system. I got a book, drew my first Punnett squares, and within about a year I was producing true lines of different colors. I knew at that point that this was probably the coolest field ever."

After receiving a baccalaureate from the University of Saskatchewan and working in a molecular virology laboratory in Munich for a year, Eichler enrolled in 1991 in the genetics program at Baylor University. Though he and his Canadian wife struggled with the climate and culture shock of living in Houston, it was the perfect place for Eichler scientifically. He began investigating the genetic disorder fragile X syndrome and "absolutely fell in love with research." His faculty adviser, David Nelson, was "a brilliant scientist and mentor who encouraged a lot of free thinking," Eichler says. "He didn't lord over me at all but let me hang myself with my own proposals."

Fragile X introduced Eichler to the instability of the genome. It occurs when mutations make a particular part of the X chromosome much longer than usual, inactivating a gene critical to development of the brain and other parts of the body. "The idea that an unstable region of the genome could increase the probability of a disease a hundredfold or a thousandfold—that's the idea I fell in love with," Eichler says. "I haven't strayed far from those roots."

While at Baylor, Eichler also began working on a study associated with the Human Genome Project, which was just then getting under way. He was attaching short DNA probes to portions of the X chromosome when he noticed that the probes also were binding to parts of chromosomes 2, 12, 16, and 22. "That was odd," Eichler recalls. It was as if portions of human DNA had been copied and scattered across the genome. "I began to think, 'How widespread is this?'"

In 1997 Eichler moved to Case Western Reserve University, where he continued investigating the genome's structure. During those years, duplications in the human genome were becoming a big problem for the Human Genome Project. When DNA is broken into pieces for sequencing, duplications make it hard to put the pieces back together, because one copy can be mistaken for another. Eichler and his coworkers took on the computer-intensive job of calculating the frequency of duplications from data being generated by both the public and the private sequencing efforts. Using PCs from CompUSA and fans from K-Mart to keep the computers cool, they found "there was a lot more duplication than anyone had thought," Eichler says.

His team continued to study duplications after the release of the draft human genome in 2000, and they discovered that many were occurring in particular "bad neighborhoods" of the genome. There, multiple copies of DNA sequences made the genome susceptible to further rearrangements through a process known as nonallelic homologous recombination (see "Swapping Segments," this page). The DNA in those regions seemed to be "churning," continually rearranging itself from one generation to the next. Eichler was sure those rearrangements had consequences for human evolution and health. But what were they?

		Many structural variants in the human genome arise when the male and female sex cells (egg and sperm) are preparing chromosomes to pass on to the next generation. During this process, the two members of each chromosome pair line up next to each other and swap segments through a mechanism known as recombination. But sometimes the chromosomes misalign. Duplications in the genome cause the wrong parts of chromosomes to line up next to each other, so that when the chromosomes swap parts, genes are added to one chromosome and deleted from another. The result is a new structural variant—an evolutionary experiment ready to be tested against nature. —S.O.

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