This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting information files.įunding: This study was supported by a supplemental grant awarded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ). Received: MaAccepted: JPublished: July 20, 2021Ĭopyright: © 2021 Rafferty et al. They also underscore the strength of the isogenic mosaic Down syndrome model system for “unmasking” cellular changes arising from a trisomy 21 imbalance.Ĭitation: Rafferty K, Archer KJ, Turner K, Brown R, Jackson-Cook C (2021) Trisomy 21-associated increases in chromosomal instability are unmasked by comparing isogenic trisomic/disomic leukocytes from people with mosaic Down syndrome. In summary, these results showed a trisomy 21-associated, age-related increase in SCINF. Similarly, a longitudinal assessment (mean time interval of 3.9 years range of 2 to 6 years) of 18 participants showed a mean 1.63-fold increase in SCINF within individuals over time for their trisomic cells (P = 0.0186), compared to a 1.13-fold change in their disomic cells (P = 0.0464). Moreover, a significant Age x Cell Type interaction was noted (P = 0.0113), indicating the relationship between age and SCINF differed between the trisomic and disomic cells. The daughter binucleates also showed significantly higher levels of abnormal patterns in the trisomic (1.68 ± 1.21) compared to disomic (0.35 ± 0.45) cells (P <0.0001). A cross-sectional assessment of 69 people with mosaic Down syndrome (ages 1 to 44 mean age of 12.84 years) showed a significantly higher frequency of micronuclei in their trisomic (0.37 ± 0.35 ) compared to disomic cells (0.18 ± 0.11)(P <0.0001). By comparing values in their isogenic trisomic/disomic cells, we obtained a measure of differences in SCINF that are directly attributable to a trisomy 21 imbalance, since differential effects attributable to “background” genetic factors and environmental exposures could be eliminated. To achieve this aim, we quantified SCINF in people with mosaic Down syndrome using a cytokinesis-blocked micronucleus assay. The primary aim of this study was to determine if germline trisomy 21 is associated with an increase in spontaneous somatic cell chromosomal instability frequencies (SCINF). However, the cellular changes that arise in somatic cells due to this aneuploid condition are not fully understood.

Down syndrome, which results from a trisomic imbalance for chromosome 21, has been associated with 80+ phenotypic traits.

Mosaic down syndrome celebrities