Viability of carriers of chromosomal abnormalities depends on genomic dosage of active ribosomal genes (rRNA genes)

The genomic dosage of active (transcription-capable) ribosomal genes (AcRG) was determined in the genomes of 172 individuals, carriers of various chromosomal abnormalities: 116 individuals with numerical autosomal abnormalities (Down syndrome and Robertson translocations), 36 individuals with numerical abnormalities of gonosomes (Klinefelter, Turner, trisomy X, and disomy Y syndromes), and 20 carriers of various structural abnormalities of chromosomes. In the control sample of healthy individuals with a normal karyotype (N = 318), the AcRG number varied from 120 to 190 copies with mean of 150 ± 1 copies per diploid genome. In all the studied samples of carriers of chromosomal abnormalities, the genomic dosage (GD) of AcRG does not exceed the limits of variation of this feature in the control sample. However, in all the samples, the characteristic differences in the GD of AcRG were revealed. In accordance with the expectation, in patients with Down syndrome, the mean GD of AcRG was 10% higher, and in carriers of Robertson translocations, the maximum AcRG dose was 20% less than in the control. It can be concluded that about 10% of patients with Down syndrome and up to 50% of carriers of Robertsonian translocations die in the prenatal or early postnatal period because of excess or deficiency of AcRG in their genomes. A significant narrowing of the limits of the variation of the GD of AcRG in a sample of age-specific (over 10 years) patients with Down syndrome in comparison with the newborns was revealed. Obviously, Down syndrome carriers with low and high doses of AcRG predominantly die during the first years of life. The GD of AcRG of carriers of numerical anomalies of gonosomes predominantly fall into the region of medium, adaptive doses, and the carriers of structural chromosomal abnormalities predominantly survive when the dose of AcRG in the genome is greater than the mean in the control sample. For the first time, data on the association of the viability of carriers of different variants of chromosomal abnormalities with the number of active copies of rRNA genes in their genomes are presented.