Genome Sequencing and Family CMT DNA History

March 2, 2011

DISCOVER Magazine – January-February 2011 – page 25

(only first two paras are on line at the magazine site)

A decade ago, sequencing the DNA in a person's entire genome cost up to $1

billion, a price so prohibitive that only a few genetics pioneers had the honor

of having it done. In 2010 the cost per genome tumbled to less than $10,000,

making it possible to study DNA variations within a single family. Almost

immediately such familial genome sequencing proved its value, uncovering

mutations responsible for diseases caused by defects in a single gene. " There

are literally hundreds, if not thousands, of diseases falling into this

category. This approach will allow us to very quickly find the genetic culprit, "

says Leroy Hood, a geneticist at the Institute for Systems Biology in Seattle.

Earlier efforts to hunt down disease-causing genes—so-called genomewide

association studies—frequently came up empty-handed because medical researchers

had to take cost-saving shortcuts. Instead of trolling an individual's entire

genome, they limited their search to DNA regions where variations are most often

seen across large populations. " It was assumed that common variants might be

responsible for common diseases, but many diseases turn out to have many

different rare variants at their root, " says Lupski, a medical geneticist

at Baylor College of Medicine in Houston. " That's why the power of whole-genome

sequencing blows us away. It's the only way we can get at these rare variants "

Lupski himself suffers from CMT … that reduces senation in the limbs. Although

neither of his parents had the condition, three of his seven siblings are also

affected by it. " For 20 years, we've been looking for the gene and mutation

behind my family's neuropathy, but we never found the variant,'' he says. Then,

in 2010, collaborating with his colleague Gibbs and other Baylor

geneticists, Lupski sequenced his own genome – and " Boom! We found it, " he says.

(Each of his parents, it turns out, carried a different recessive muation of the

same gene. Consequently, only their children who in herited one from each parent

developed the disorder.)

… goes on to other genetic disorders.

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