The name of one thing or another, in isolation, may seem arbitrary, as poets and artists have suggested from time to time. Scientists, however, have a different perspective. They cannot accept, as a painter once declared, that the “precision of naming takes away from the uniqueness of seeing.” For scientists, names don’t necessarily exist in isolation. Rather, names may be elements in a system of names, a nomenclature.

Scientists agree on nomenclatures—which, admittedly, hold little or no intrinsic interest—because they ease communication and prevent confusion, which can otherwise settle over a subject like a fog. One such subject, cytogenetics, has dispelled fogginess for quite some time, thanks in part to the International System for Human Cytogenetic Nomenclature, which is the current official classification system used to describe structural chromosome rearrangements. While it has served admirably, this system is due for an update.

The current nomenclature evolved to systematize communications about chromosomal abnormalities at the microscopic level, which made sense because most observations were derived from the comparison of karyograms, or pictures of chromosomes. But now, with observations at the DNA level becoming increasingly common, researchers and clinicians alike are having difficulty communicating. They lack a clear consensus about how they should describe genetic abnormalities that occur at the DNA level when chromosomes swap, delete, or add parts. As a result, inconsistencies are creeping into research and clinical reports.

Determined to act before an already thickening fog can envelop cytogenetics is a team of researchers at Brigham and Women’s Hospital (BWH). It proposes a new classification system—Next-Gen Cytogenetic Nomenclature—that may standardize how structural chromosomal rearrangements are described.

The system was first presented online April 17 in The American Journal of Human Genetics, in an article entitled “Describing Sequencing Results of Structural Chromosome Rearrangements with a Suggested Next-Generation Cytogenetic Nomenclature.”

According to the article’s authors, advances in next-generation sequencing methods and results from BWH’s Developmental Genome Anatomy Project (DGAP) revealed an assortment of genes disrupted and dysregulated in human development in over 100 cases. Given the wide variety of chromosomal abnormalities, the researchers recognized that more accurate and full descriptions of structural chromosomal rearrangements were needed.

“Currently, most DNA sequencing reports only provide nucleotide numbers of the breakpoints in various formats based on the reference genome sequence alignment,” said lead study author Zehra Ordulu, M.D., BWH department of obstetrics, gynecology, and reproductive medicine. “But there are other important characteristics of the rearrangement—including reference genome identification, chromosome band level, direction of the sequence, homology, repeats, and nontemplated sequence—that are not described.”

The proposed system addresses these characteristics and builds upon the current classification system. In particular, the proposed system would incorporate an online tool called the BLA(S)T Output Sequence Tool of Nomenclature, or BOSToN. The tool works by aligning nucleotide sequences to reference human genome sequences. After processing the genetic information, the end result is the Next-Gen Cytogenetic Nomenclature that researchers and clinicians can then incorporate into their reports.

“BOSToN will reduce errors in sequence assessment and save time in generating nomenclature,” asserted senior study author Cynthia Morton, Ph.D., BWH director of cytogenetics, who added that accuracy and timeliness are “both of critical importance in the clinical setting.”

“As scientists we are moving the field of cytogenetics forward in the clinical space,” Dr. Morton concluded. “We will be able to define chromosomal abnormalities and report them in a way that is integral to molecular methods entering clinical practice.”

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