Ahead of other U.S. academic institutions, The Johns
of Medicine and its
McKusick-Nathans Institute of Genetic
Medicine have pooled resources to obtain a commercial
system capable of processing hundreds of DNA samples and
determining up to 600,000 genotypes a day.
The $1.5 million system, purchased from Illumina Inc.,
of San Diego, Calif., has been installed and tested and
should be fully operational by September. Part of the
shared genetics resources at Johns Hopkins, the system will
use both pre-made panels of known genetic sequences and
research-specific panels of genes, designed in house, to
identify genetic changes in DNA samples.
"In addition to offering a lower cost to researchers,
our flexibility should set us apart from what is available
from companies," said Alan Scott, director of Johns
Hopkins' Genetics Resources
Core Facility and one of the forces behind getting the
new genotyping system. "Quite a few research programs here
require genotyping hundreds to thousands of tissue samples,
and other researchers may have been reluctant to take on
such tasks because the work couldn't be done nearby. Now
we'll be able to offer these services right here at
The new system, called BeadLab because of the
technology it uses, can examine up to 96 different samples
and determine more than 100,000 genotypes in a single
experiment. A genotype is a description of an individual's
sequence of genetic building blocks (A, G, T and C) and can
be compared to others' to help scientists identify genes
involved in disease.
Most of the human genome's 3 billion building blocks
occur in the same order in all humans. But everyone also
has occasional substitution of one genetic building block
for another. If a particular spot has a common variation
(i.e., some people have an A instead of the usual C), that
position is said to have a single nucleotide polymorphism,
or SNP (pronounced "snip"). Several million SNPs already
Geneticists have successfully correlated SNPs or other
mutations with the incidence of some rare diseases such as
cystic fibrosis. But determining genetic contributors to
and causes of such common diseases as cancer has been a
difficult, piecemeal process because these conditions
involve multiple genetic changes that combine to affect
health or disease.
"This genotyping technology lets you rapidly survey
what amounts to the entire human genome for regions linked
to a condition, and then, separately, to delve into the
fine detail of very small regions of DNA to figure out
what's really happening," Scott said.
With the appropriate controls and experimental setup
by trained technicians, the system determines the genotypes
of all the samples and produces a score that rates the
accuracy of the result.
"These genotypes can then be correlated with patient
characteristics, health, tissue type or whatever it is
you're studying," said Aravinda Chakravarti, director of
the McKusick-Nathans Institute. "Instead of spending years
just to get genotype information across the genome, now we
can spend our time analyzing the data, looking for multiple
genes rather than finding them one at a time. With this
system we're well on our way to being able to do
large-scale studies of complex human genetic diseases and
to investigating the biological basis of individuals'
susceptibility to disease."
The Illumina system's BeadArray technology uses
dimpled fiberoptic strands in bundles no thicker than a
pencil lead, each holding tens of thousands of tiny beads.
Each bead is labeled with one of up to 1,300 DNA tags to
unmask the version of a specific SNP in the sample. The
fiberoptic bundles are then arrayed as in a 96-well
The new facility will be housed at the Johns Hopkins
Bayview Research Campus near the Center for Inherited
Disease Research, a Johns Hopkins operation funded by a
federal contract. As more researchers begin to need and use
the technology, Scott hopes the system is used to determine
roughly 200,000 genotypes per day.
Scott noted that the high-throughput genotyping system
complements other services offered by the Genetics
Resources Core Facility, including the DNA Fragment
Analysis Lab and the DNA Analysis Facility. Both can
determine research-specific genetic sequences that can't
otherwise be studied.
Related Web sites
The Genetics Resources Core Facility