@daphnarothschild.bsky.social
Together, these findings causally link rRNA variation to human traits, disease, and establish that ESs have distinct and important functions in human physiology.
8/8
Rare mutations are sporadic across the rDNA arrays, but es15l and es39l subtype variants show higher chromosome specificity to chr14 and chr21. This could potentially point to regulation of adiposity and body dimension traits by regulating chromosome specific rDNA arrays.
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In contrast, most of the rRNA 18S and 28S regions are conserved and we showed that *rare* mutations at conserved regions associate with diseases. These included common and rare diseases such as cancer and acute myocardial infarction.
6/8
We found that ESs have distinct functions where es15l associated with adiposity, es39l with body dimensions, and es27l with blood-related traits and diseases.
(See example QQ plots showing IGF-1 association with the es27l, and height associated with es15l and es39l).
5/8
The common heritable variants which we term ribosome *subtypes* affect body dimensions, adiposity, blood traits and diseases. Importantly, these variants are found in Expansion Segments (ES), solvent exposed regions of the ribosome that we know little about their function.
4/8
We found tens of heritable variants found in *high* rDNA copy numbers. But the vast majority of variants (~1000 variants) can be described as mutations found *sporadic* between the rDNA and they show low heritability, potentially somatic in origin.
3/8
In our *previous* study we made an atlas of rRNA sequence variants from translating ribosomes and showed that their *expression* associated with development and cancer.
*Here* we analyze the UK Biobank cohort and ask if changes in *rDNA* variations affect human physiology.
2/8
Ribosomal RNA (rRNA) genes are found in hundreds of copies in the human genome.
Do sequence variations in these paralogs change the ribosome function? Yes!
I am excited to share our new preprint @mbarnalab @jkpritch in collaboration with Calico:
www.medrxiv.org/content/10.1...
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