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The Wadsworth Center has applied for a NIH grant
to study the implications of sequencing exomes, the
protein-coding regions of the genome, in a subset of
newborns. The project would compare genetic find-
ings with those from traditional newborn screening
for select infants with screen-positive results or con-
firmed disorders.
“It’s exciting, but it’s scary too,” said Carlos Saavedra-Matiz, MD, Wadsworth’s newborn screening DNA
laboratory supervisor. “What are we gonna get? The
clinical interpretation of the results is the biggest
challenge.”
In the near term, NGS in newborn screening will
probably be limited to targeted gene sequencing as
a second tier test to confirm initial screen positives
and decrease false positives. For example, a group of
states in the Great Lakes region is evaluating a next-gen technique to sequence the gene that causes cystic
fibrosis, so scientists can search for a second mutation
in newborns who screen positive for a cystic fibrosis
mutation panel. The Wadsworth Center is seeking
funding to develop and evaluate a second-tier test
for severe combined immunodeficiency that would
involve NGS to decipher 20 whole genes.
In the long term, the possibilities seem endless for
newborn screening and other core PHL programs.
In September 2012, Life Technologies introduced its
benchtop Proton Platform, capable of sequencing the
entire human genome for $1,000. Next year, Felton
said, the company will introduce a third-generation
semiconductor sequencing chip for the Proton platform with potential to halve the cost. The aim, he said,
is to make the technology “very small, inexpensive
and fast.”
Microbiologist Kaye Eckmann preparing Salmonella isolates for PFGE subtyping to
support a foodborne contamination test at the Washington State Public Health Laboratory
Genetics has used the technique to “read” a 3,272
base-pair DNA molecule and a 7,249 base-pair viral
genome with sequence-specific, heavy-atom
labeled DNA.
Perhaps the most exciting NGS technology of many
under development is direct visualization of DNA base
pairs using atomic-resolution, transmission electron
microscopy. A team of scientists from Harvard
University, the University of New Hampshire and ZS
But in the final analysis, purchasing equipment will
be the easy part. Even after manufacturers reach what
Sauders calls “the sweet spot of cost and speed,” it
will be up to public health leaders to sort through
it all, decide the optimal uses for new technologies,
assure appropriate staff training, and develop quality metrics, bioinformatics capabilities and regulatory
benchmarks. Already, the first accreditation standards
for clinical laboratories performing NGS are in effect,
released by the College of American Pathologists
last summer.
CDC’s Ribot predicts that standardization—a hallmark
of PulseNet testing—”is going to be very different
from what it is today.” He said, “We may not be able to
standardize every element of how the sequencing is
generated, because it’s so platform-specific. Standardization will most likely be at the data level, with strict
parameters for data quality and data analysis.”
Ultimately, NGS represents both opportunity and
challenge. It is, said Fontana, “the brave new world.” u
