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of the diseases unique to Finland is a children's brain disorder
called neuronal ceroid lipofuscinosis, or NCL. To get the disease,
a child must inherit a mutated gene from each parent. Though it
strikes only about 50 families a year, NCL is especially cruel.
Children with the disease appear normal at birth, but by the age
of 1 they begin to go blind. Eventually, they lose their brain function
and die a slow, brutal death. Because no one knew what caused the
disorder, there was no way to prenatally diagnose children with
1988, Peltonen was contacted by a neurologist who had been treating
these children. "She came to me and said, 'Something must be
done; this is such a terrible disease. We have to solve the basis
of this. We have nothing to offer parents. It's very frustrating
to them.' "Peltonen approached the parents of the affected
children, and each agreed to participate in a project to find the
genetic cause of the disease. After collecting blood samples from
the healthy parents and their sick children, Peltonen set out to
scour their DNA for genetic markers - landmarks she could use to
narrow the location of the gene. Meanwhile, she also searched their
genealogical histories to try to find the origin of the disease.
the time, the human genome was not well-known, so hunting for genes
was an agonizingly slow process. As Palotie explains: "This
was very primitive compared to today's technology. You would run
these markers around the genome, then narrow the region where the
defective gene was. If some of these markers are always similar
in affected individuals, by having 400 markers from all places of
your genome, you usually hit with a few of them. Then you try to
pull out more of these markers for areas that are similar between
these patients. Then you get the statistical confidence that this
is the place, but you're still far away. In the end you have to
combine various mapping techniques."
took Peltonen and another scientist seven years to find the gene.
In January 1995, they traced the mutation to a site on Chromosome
1. When Peltonen learned what the gene actually did, she was amazed:
Its function is to make a protein that removes fatty acids, or lipids,
from the cells. If this process is disrupted - as it is in babies
with NCL - the brain cells die. This finding, it turns out, was
significant not just for NCL, but for understanding the molecular
process behind other brain disorders. "This is so fascinating,"
says Peltonen, "because we'd have never thought that something
involved in the lipid metabolism would be so dramatic for brain
cells. This has now become obvious in many other diseases. So in
many ways it opened a new concept of how crucial this lipid modification
of the protein is for brain cells.
think this is a beautiful story," she adds, "how a globally
uninteresting disease in a small corner of the world opened a new
field of research. I think it's an educational story. You can't
always bet which project produces the most valuable biological information."