Molecular cytogenetic characteristics of small supernumerary marker chromosomes 15 and 22 in asymptomatic carriers

Yurchenko DA, Markova ZhG, Minzhenkova ME, Vorontsova EO, Shilova NV
About authors

Research Centre for Medical Genetics, Moscow, Russia

Correspondence should be addressed: Darya A. Yurchenko
Moskvorechye, 1, Moscow, 115522, Russia; ur.liam@vblahsad

About paper

Funding: this work was carried out at the expense of budgetary funds within the framework of research topic № 122032300370-1, “Study of Structural and Functional Features and Mechanisms of the Formation of Chromosomal Abnormalities and Genomic Imbalance.”

Author contribution: Yurchenko DA — study design, development of homemade DNA probes, FISH diagnosis and data interpretation, manuscript writing; Markova ZhG and Minzhenkova ME — FISH analysis with commercial DNA probes; Vorontsova EO — implementation of the protocol of FISH with homemade DNA probes; Shilova NV — study concept and design, discussion, scientific editing of manuscript.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Research Centre for Medical Genetics (protocol No. 4/2 dated 19 April 2021). The patients submitted the informed consent to participation in scientific research.

Received: 2023-10-23 Accepted: 2024-01-06 Published online: 2024-01-31

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be identified unambiguously by standard cytogenetic methods. A comprehensive approach involving the use of molecular cytogenetic methods is required for the more thorough morphological assessment of such chromosomes, as well as for the development of strategy for genetic counseling of the patients being the sSMC carriers. It is widely accepted that the development of abnormal phenotype by the patients having sSMC in their karyotype is associated with the presence of euchromatic region material in the marker chromosome. Therefore, it results from the presence of relatively large DNA copy number variations (CNVs) in the form of duplication, triplication, and more increased copy numbers; which are localized in the pericentromeric region of the appropriate chromosome. Pericentromeric CNVs can be involved in the chromosome imbalance in asymptomatic carriers of sSMC as well, however, the boundaries of such imbalance have not been clearly identified. The study was aimed to acquire additional information about the genomic topology of the DNA regions insensitive to the genes copy number increase. FISH analysis with commercial and homemade DNA probes was performed in 18 carriers of sSMC 15 and 22 having no clinically significant phenotypic abnormalities. The molecular cytogenetic testing showed that pericentromeric euchromatic regions sized 1.2 Mb and 714 kb, respectively, were found in 33% of cases (6 out of 18). We assume that these regions comprise no potentially dosage-sensitive genes.

Keywords: FISH, sSMC, CNV, pericentromeric euchromatin, homemade DNA probe