Copy Number Variations of Human Ribosomal Genes in Health and Disease: Role and Causes

Area of Science:

• Genetics
• Molecular Biology
• Aging Research

Background:

• Ribosomal DNA copy number (rDNA CN) associations with aging and disease are debated.
• Existing data are contradictory, often due to varying quantification methods.

Purpose of the Study:

• To quantify rDNA CN in human cells using a hybridization technique.
• To investigate rDNA CN in healthy controls, schizophrenia (SZ), cystic fibrosis (CF), and mild cognitive impairment (MCI) patients.
• To analyze rDNA CN in centenarians and across previously published data.

Main Methods:

• Human cell rDNA CN determined via hybridization.
• Study included healthy controls (HCs), SZ, CF, and MCI patients (N=1124).
• Analysis combined new data with prior studies (total N=3264), including 105 individuals aged 90-101.

Main Results:

• Increased rDNA CN observed in SZ (534 ± 108) and CF (567 ± 100) groups compared to HCs (422 ± 104).
• Reduced rDNA CN found in MCI patients (330 ± 60).
• rDNA CN showed decreased variation in older age subgroups and was largely stable over time and across organs.

Conclusions:

• rDNA CN is a stable genetic trait associated with specific diseases.
• Age- and disease-related differences in rDNA CN may stem from selective elimination of individuals with extreme values.
• Rare changes in rDNA CN can occur under chronic oxidative stress.