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Epigenetics could explain puzzle of diabetes inheritance
According to research led by Queen Mary University of London (QMUL), a mother's diet during pregnancy can permanently affect her offspring, as measured by how her diet affects her ribosomal DNA (rDNA). This discovery could be why many human gene studies cannot fully explain how certain diseases, such as type 2 diabetes and obesity, are inherited.
The ribosome is a complex machine within all living cells. It reads messenger RNA (mRNA) then links proteins to the amino acids specified. Ribosomes have two major components: (1) a small ribosomal unit to read RNA, and (2) a large unit that joins mRNA to amino acids — thereby making polypeptide chains. Together the two units are known as a translational apparatus.
"This could be the reason why we've only so far been able to explain a small fraction of the heritability of many health conditions; which makes a lot of sense in the context of metabolic diseases, such as type 2 diabetes."
Within the in-utero environment, environmental factors act alongside genetic factors to determine a person's attributes. When offspring are in the womb, they experience their mothers environmental influences (like diet, stress, and smoking). These influences continue to affect offspring even when they are adults. 'Developmental programming' is a large contributor to our obesity epidemic.
A major contributor in this process is 'epigenetics' — modifications to genes that control when or if, certain genes function. One modification involves tagging DNA with compounds called methyl groups.
The team compared offspring of pregnant mice fed a low protein diet - 8 per cent protein - to a normal diet of 20 per cent protein. After being weaned, all mouse pups were fed the same normal diet with 20 per cent protein. The team then looked at the difference in DNA methylation in pups born to mothers exposed to low protein and normal protein diets.
These epigenetic effects occur in a critical developmental window, while the offspring is in-utero, to create a permanent effect remaining throughout adulthood. A pregnant mother's low protein diet is therefore likely to have more severe consequence on her offspring's epigenetic state and weight, than an offspring's own diet after weaned from its mother.
In any given genome, there are many copies of rDNA, and Professor Rakyan and colleagues found that not all copies of rDNA responded epigenetically. In offspring from mothers fed low protein diets, only one form of rDNA — the 'A-variant' — appeared to undergo methylation affecting weight.
This means an epigenetic response in any given mouse is determined by their own genetic variation of rDNA. Those mice with more A-variant rDNA end up being smaller.
"Even though all mice in the study were bred to be genetically identical, we found that rDNA in individual mice is not genetically identical. That even within an individual mouse, different copies of rDNA were genetically distinct.
Heritability of type 2 diabetes — the risk of disease explained by genetic factors — is estimated to be between 25 and 80 per cent in different studies. However, only about 20 per cent of heritability of type 2 diabetes is explained in people with the disease. Genetic variation in rDNA could explain some missing heritability.
These findings also complement other studies where mice put on high fat diets have pups with increased rDNA methylation — suggesting methylation is a general stress response. This may explain our rise in obesity happening around the world.
About Queen Mary University of London
Within a cell, the (5) rough endoplasmic reticulum is studded with protein
manufacturing ribosomes (dark blue dots), giving it a "rough" appearance .
Image Credit: Wikipedia.org