Reply to Hochstenbach et al (original) (raw)

The introduction of the term ‘molecular karyotyping’ was a conscious decision, being well aware of both its limitations and advantages. Hochstenbach et al1 summon the shortcomings of this new term in genetics. Here, we would like to summarize the advantages of using this terminology and pinpoint some shortcomings in their reasoning.

The term karyotype was introduced by Levitsky. At that time, it was meant to describe nuclear morphology (as its Greek meaning explains). In 1931, Levitsky2 wrote ‘Me personally, used the term karyotype to define the characteristics of the nuclei from one or a group of organisms.’ As in plant nuclei chromosomes were easily visualized, the karyotyping or looking at nuclei became synonymous. Because of this, the term has taken on its current definition as describing the particular chromosome complement of an individual, as defined by the number and morphology of the chromosomes. Thus, the meaning of the word ‘karyotype’ has evolved and is time and context dependent.

Karyotyping was the first genome-wide screening tool for chromosomal imbalances and – in addition – enables the identification of chromosomal translocations. Cytogenetics is the discipline in genetics that studies chromosomes and analyses karyotypes and most cytogeneticists, especially human cytogeneticists, are experts in karyotyping. In analogy with karyotyping, genome-wide array comparative genomic hybridization (CGH) or hybridization of single-nucleotide polymorphism (SNP) arrays enables the detection of genomic imbalances, albeit cannot, as of yet, detect chromosomal translocations. On the other hand, conventional karyotyping alone often shows aberrations that cannot be assigned to a chromosomal band and is not able to detect small aberrations or structural exchanges of similar banding pattern. ‘Molecular karyotyping’ is therefore the logical term for the different new molecular techniques for genome-wide profiling of chromosomal aberrations and places the technology used for these purposes within the realm of the expertise of cytogeneticists.

Rather than giving a new meaning to the word karyotype, a new word or expression ‘molecular karyotyping’ was coined. This word is not the same, nor meant to be the same as ‘karyotype’. Its meaning is: ‘A genome-wide intensity ratio profile comparing patient versus reference DNA’. An overview of genomic imbalances is derived using DNA from a mixture of cells in all stages of the cell cycles without a view of chromosome morphology. The term karyotype is used here as a metaphor, and the combination of molecular and karyotype creates a novel expression. The most important aspect of a language is that communities of people understand the same when using certain words. The genetics community is such an entity and it is our feeling that ‘molecular karyotyping’ better captures the spirit of the technique as compared with the introduction of yet another novel term ‘segmental aneuploidy profiling’.

Moreover, genome-wide array CGH or hybridization of SNP arrays are not restricted to ‘segmental aneuploidy’, the new term proposed by Hochstenbach et al.1 The technique is also capable of showing whole chromosome aneuploidies. Hochstenbach et al1 argue that the term molecular karyotyping is already in use to indicate a flow cytometric karyotype. As flow cytometry is not implemented in medical genetic laboratories, the term does not create confusion in our discipline.

In conclusion, ‘molecular karyotyping’ is a simple term that was independently introduced by at least three groups.3, 4, 5 Hence, the term seems to both have the backing and meet the needs of the medical genetics community.

References

  1. Hochstenbach R, van Amstel HK, Poot M : Microarray-based genome investigation: molecular karyotyping or segmental aneuploidy profiling? Eur J Hum Genet 2006; 14: 262–265.
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  2. Levitsky GA : Morphology of the chromosomes and the notion of karyotype in the systematics. Bull Appl Gen Plant Breeding 1931; 27: 187–240.
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  4. Rauch A, Ruschendorf F, Huang J et al: Molecular karyotyping using an SNP array for genomewide genotyping. J Med Genet 2004; 41: 916–922.
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  5. Vermeesch JR, Melotte C, Froyen G et al: Molecular karyotyping: array CGH quality criteria for constitutional genetic diagnosis. J Histochem Cytochem 2005; 53: 413–422.
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Acknowledgements

We thank Irina Balikova for the English translation from the original Russian article written by Levitsky.

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Authors and Affiliations

  1. Centre for Human Genetics, University of Leuven, University Hospital Gasthuisberg, Leuven, Belgium
    Joris Robert Vermeesch
  2. Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
    Anita Rauch

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  1. Joris Robert Vermeesch
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  2. Anita Rauch
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Correspondence toJoris Robert Vermeesch.

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Vermeesch, J., Rauch, A. Reply to Hochstenbach et al.Eur J Hum Genet 14, 1063–1064 (2006). https://doi.org/10.1038/sj.ejhg.5201663

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