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Screening Today for a Healthier Tomorrow

Mimi Padmabandu
| Jun 11, 2013

Blue Dots Cancer whiteCell smallIn 2002, following the Human Genome Project’s draft genome assembly, a team of scientists known as BlueGnome developed a novel mathematical technology for analyzing sequencing data. Today, the Cambridge-based BlueGnome is a leading provider of genetics solutions to screen for chromosomal abnormalities, with significant implications for cytogenetics and in vitro fertilization (IVF). Last year, Illumina announced the acquisition of BlueGnome, opening up new possibilities for screening technologies that impact developmental delay, infertility, and cancer.

Investigating Genetic Causes of Developmental Delay

Developmental delay is a term used to describe children who are typically smaller than average and slow to achieve developmental milestones. Delay may be manifested in motor, speech and language, cognitive, or social skills. Developmental delay is estimated to have a genetic basis in about 50% of cases (such as Cri Du Chat syndrome, DiGeorge syndrome, and Down syndrome) though the specific region of the genome responsible for causing a condition is not always known. Recently, due to advances in microarray technology, a large number of microdeletion and microduplication syndromes—including 17q21.31 and 15q13.3 microdeletions—have been identified as causes of developmental delay.

Comparative genomic hybridization (CGH) is a molecular cytogenetic method for analyzing copy number variations in samples without the need for cell culture. Array CGH (aCGH) enables chromosome screening at a much higher resolution than traditional metaphase chromosome techniques. Array CGH can detect chromosomal abnormalities ranging from whole-chromosome aneuploidy to microdeletions and microduplications. The high resolution of detection has driven widespread adoption of aCGH to assess the risk of developmental delays and other conditions.

Improving IVF Success

There are many potential underlying causes of infertility, including physiological, biochemical, and genetic conditions. Since the first case over 30 years ago, IVF treatment for infertility has become a highly refined process, improved by advances such as intra-cytoplasmic sperm injection (ICSI), the direct injection of sperm into eggs. Copy number imbalance—which denotes aneuploidy, or an abnormal number of chromosomes—has gained prominence as an important factor in the field of IVF. Many human eggs cultured via IVF contain abnormal chromosome numbers, and this aneuploidy can often cause IVF failure and pregnancy loss.

Preimplantation genetic screening (PGS) is a method used to identify embryos at risk of copy number imbalance. Initially, PGS was conducted using fluorescence in situ hybridization (FISH), but the use of this technique has declined in recent years. The 24sure test developed by BlueGnome has since become a widely adopted PGS test for examining all 24 chromosomes from a single cell prior to implantation. Copy number screening has developed as a means of improving pregnancy outcome by implanting only euploid embryos (those with the correct number of chromosomes).

Detecting Genetic Changes in Cancer Cells

Copy number imbalance—including subchromosomal gains, losses, and amplifications—can also occur via de novo mutations in a subset of cells. In cancer cases, chromosomal abnormalities involved in the normal-to-cancer transformation can be detected by aCGH technology. For example, array CGH can detect unbalanced chromosomal translocations, which fuse normally distant genes to form active gene products and can result in oncogene overexpression. BlueGnome provides array CGH platforms that detect these subchromosomal features in cancer cells. The CytoSNP 850K array, containing over 850,000 SNPs across the genome with enriched coverage within cytogenetic relevant genes, was presented at the 2013 ESHG meeting in Paris this past weekend, together with BlueFuse, a streamlined annotating and reporting software that enables a common view across different array technologies provides the path to future innovations in cytogenetics.

Stay tuned for more advances as BlueGnome and Illumina strive to provide integrated solutions for reproductive health and cancer.