Computational and genomic tools have enabled researchers to explore the human genome and make many associations between various characteristics and genes or gene variants. But many parts of the human genome are highly repetitive, which can make them very challenging to analyze with standard tools. There have also been some assumptions that these repetitive regions are not that important to human health. But research is challenging those notions.
New work reported in Cell Genomics has used genomic data from tens of thousands of people to analyze a highly repetitive region of the human genome that encodes for portions of a cellular machine known as the ribosome. Ribosomes are crucial and are found in all cells; they are responsible for translating messenger RNA molecules, a process which generates proteins, This work has suggested that when people carry high levels of ribosomal DNA, their risk of disease also increases.
In this work, the investigators assessed data from 500,000 individuals, contained in the UK Biobank; they looked for differences in the levels of ribosomal DNA in every sample, then compared those results with health data and medical records for each person.
This showed that the ribosomal DNA copy number in a person was strongly associated with markers of systemic inflammation that are well known, like the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). These statistical links were seen across ethnicities, which could indicate that ribosomal DNA copy number levels are an indicator of a person's risk of future disease.
"Our research highlights the importance of analyzing the whole genome to better understand the factors impacting on our health," said senior study author Professor Vardhman Rakyan, of the Genomics and Child Health at the Blizard Institute at Queen Mary, University of London. This study is also an example of how having access to large biobanks allows us to make unexpected discoveries, and provides new avenues for harnessing the power of genetics to understand human diseases."
Study co-author Professor David Evans of the University of Queensland's Institute for Molecular Bioscience noted that scientists have long had difficulty explaining the genetic basis of a variety of common diseases and traits. "Our work suggests that at least part of this missing heritability resides in difficult to sequence regions of the genome such as those encoding ribosomal copy number variation."