540
The study’s authors found that cfDNA testing >1,900 pregnant women, however,
correctly fl agged trisomy 21 > 40 % of the time. If cfDNA testing were to be used as
a primary screen, it could result in a 90 % reduction of invasive procedure. A nega-
tive result on cfDNA screening obviates the need for invasive testing and thus the
discomfort and risk to the pregnancy incurred by such testing (Greene and Phimister
2014 ). Currently, cfDNA testing is more commonly used in high-risk pregnancies;
the new technology is not typically used in all pregnancies.
Verinata Inc’s verifi ® prenatal test, launched in 2012 through a partnership with
Laboratory Corporation of America, quantifi es fetal cfDNA fragments. A
sequencing- based approach is used to identify chromosomal aneuploidies across
the entire genome. Using optimized algorithms, it analyzes DNA sequencing data to
identify fetal chromosomal abnormalities: (1) trisomy 21 with 97.2 % sensitivity
and 100 % specifi city; (2) trisomy 18 (Edwards syndrome) with 100 % sensitivity
and specifi city; and (3) trisomy 13 (Patau syndrome) with 78.6 % sensitivity and
100 % specifi city.
Sequencing Genomes of the Newborn to Screen for Genetic Disorders
More than 6,000 babies are born every year in the UK with serious developmental
disorders, but currently, only a small number of them can be diagnosed before they
begin to present patterns of symptoms. In 2011, a project in the UK led by the
Wellcome Trust Sanger Institute and the National Health Service (NHS) started
work on a plan to analyze the genomes of up to 12,000 children with physical and
mental developmental problems and multiple birth malformations in the hopes of
developing new tools to diagnose these disorders. The Deciphering Development
Disorders (DDD) program will use the resources of all 23 of the NHS Clinical
Genetics Services across the UK to collect comprehensive genomic data and to
develop clinical tools for diagnosing the genetic causes for these developmental
problems. Funded under the Health Innovation Challenge Fund, a partnership
between the Department of Health and the Wellcome Trust, the 5-year effort will
incorporate the genomic data on these children with information about their physi-
cal and mental characteristics. By linking together the expertise in genomics at the
Wellcome Trust Sanger Institute with the unique network of Clinical Genetics
Services offered by the NHS, these families can directly benefi t from the rapid
growth in the understanding of human genome. The research will use next-
generation sequencing tools to seek out CNVs, exon deletions, and single changes
in base pairs that may cause developmental disorders. The DDD project also will
lead to an expansion of the DECIPHER (DatabasE of Chromosomal Imbalance and
Phenotype in Humans using Ensembl Resources) database, which was started in
2004 to support clinical interpretation of genetic variations and provides the infor-
mation from clinical centers around the world. The dataset will enable researchers
studying child development to link genetic variants to phenotypes and to identify
potential molecular targets for treatments, as well as for diagnostics tools. The DDD
project will also carry out research with patients and health professionals to identify
and analyze the ethical issues likely to arise in the use of these tools and to work
16 Personalized Management of Genetic Disorders