Dutch-French research shows that Optical Genome Mapping (OGM) detects abnormalities in chromosomes & DNA very quickly, effectively & accurately. Sometimes even better than all existing techniques together, as they describe in 2 proof-of-concept studies published within the American Journal of Human Genetics. This new technique could transform the prevailing workflow within cytogenetic laboratories.
Human hereditary material is stored in 46 chromosomes (23 pairs). Although those chromosomes are quite stable, changes in number or structure can still occur. a well known example is down-syndrome’ , which is caused by an additional chromosome 21 (trisomy 21). an additional chromosome makes an enormous difference and easy to visualize. But all types of other, smaller changes can occur also in chromosomes. Sometimes pieces of DNA are lost (deletions), sometimes a bit is simply repeated (duplication) or it’s moved to a different place (translocation). An existing piece also can be turned over (inversion) and sometimes new pieces are inserted (insertions). These all structural abnormalities within the chromosomes can cause disease, either congenital genetic diseases, which are present from birth, almost like down-syndrome’ , or acquired disorders, when the change occurs in few cells during life which may cause cancer, like in leukemia.
Cytogenetics is that the genetic discipline that examines chromosomes for such abnormalities. To see both the massive and little changes, several complementary techniques are needed, like FISH, karyotyping and Copy Number Variant (CNV) microarrays. These are often laborious techniques that individually can only visualize a part of the above-mentioned abnormalities. Recently a latest technique has become available—Optical Genome Mapping—which more or less brings together the previous techniques. But new techniques must prove themselves in practice. At Radboud University Medical center (Radboudumc), Alexander Hoischen, professor of Genomics Technologies and Immuno-Genomics, researches new techniques for usability in clinical research and possibly later in patient care. It requires close cooperation between Radboudumc and therefore the industry involved in building latest genomic technologies, in_this case the America-based company Bionano Genomics.
Hoischen immediately mentions 2 major advantages of OGM: “We can now check out extremely long stretches of DNA, so there’s fewer pieces needed to map the whole chromosome. It’s faster and produces fewer errors. Furthermore, unlike other techniques, we don’t need to pre-process or manipulate the DNA, so we glance at the real , ‘natural’ DNA. In short: what you see is what you get.”
Automatic, objective, digital
Bionano has created a label that attaches to a selected piece of DNA that happens fairly often , but irregularly. The ever-changing distances between the labels create a singular barcode so researchers always know exactly where they’re situated within the DNA. This labeled DNA is pulled through thin long nanochannels, while a camera continuously takes pictures. Hoischen: “In this manner we will automatically, objectively and digitally record DNA at a rapid pace, and at a resolution that’s 10,000 times higher in karyotyping. it is a quite ‘cytogenetics on steroids’ due to its power & speed.”
But how well does the technology work? Two papers within the American Journal of Human Genetics provides a positive answer. Dr. Laïla El Khattabi of the Université de Paris, Hoischen, and their colleagues, tested OGM on 85 samples from patients with a hereditary disorder that had previously been examined with the quality tests (karyotyping, FISH, CNV microarray). Remarkable and exceptional: OGM found all of them . El Khattabi: “OGM can really revolutionize the detection of chromosomal aberrations. i feel it might be the foremost significant technological breakthrough within the history of cytogenetics since the CNV microarray.”
In the second paper, team of Nijmegen researchers again compared technique to the standard tests. this point they checked out the DNA of leukemia cells of 52 patients with leukemia, a hematological malignancy. Here too, OGM performed optimally by detecting all clinically known deviations. And quiet more than that. In number of cases, the technique provided better and more accurate analyzes of chromosomal abnormalities. this is often rather important, because the proper treatment often depends on this. Hoischen: “We are early adapters of various genome technologies, often with the aim of quickly applying them routinely in clinic. The very convincing data in these 2 proof-of-concept studies again place Radboudumc at the forefront of technical innovation for healthcare in human genetics. This ‘Next Generation Cytogenetics’ could replace decade old routine testing, vastly improving workflow and patient care.” this is often echoed by Dr. Marian Stevens-Kroef, Clinical Laboratory Geneticist for hematological malignancies: “OGM promises to greatly improve cytogenetic testing in patients with hematological malignancies.”
Further roll out
Radboudumc researchers Dr. Kornelia Neveling and Dr. Tuomo Mantere, first authors in both studies, also are positive about the technique. Neveling: “It may be a rather simple technology, for both the wet lab and data analysis, and that we foresee great advantages for a use in clinical setting. additionally , OGM has already helped to unravel several medical mysteries, a number of which are expecting answers for quite 20 years.”
Tuomo Mantere, former postdoc in Hoischen’s laboratory and now affiliated with Oulu University in Finland: “The easy implementation of this technique & therefore the convincing concordance with standard cytogenetic methods as presented in these 2 studies convinced me to line up OGM now in Finland also .”
The findings were published on The American Journal of Human Genetics.