In an animal study, an international team of researchers led by Medical Research Council (MRC) Harwell Institute scientist Dr. Steve Brown has uncovered several novel genes associated with age-related conditions including hearing loss, retinal degeneration and osteoarthritis.
Portrait of Anna McNeill Whistler by James Abbott McNeill Whistler, summer 1871.
Age is a risk factor for many conditions, including diabetes, cardiovascular disease, hearing loss, dementia and others, but the genes that we carry also influence whether we are more or less susceptible to these.
Not much is known about which genes influence age-related conditions, or how they do so.
To explore this further, Dr. Brown and his colleagues from the UK and France introduced new mutations at random positions in the genes of mice before they were born, and then monitored their health as they aged.
If an age-related condition developed, the team investigated which particular gene in that mouse had been mutated.
“We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged,” the scientists explained.
“In total, we identify 105 distinct mutant lines from 157 pedigrees analyzed, out of which 27 are late-onset phenotypes across a range of physiological systems.”
“Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease.”
One gene identified by the team was Slc4a10 (solute carrier family 4, sodium bicarbonate transporter, member 10).
This gene was already known to be needed for eye function, but the study linked defective Slc4a10 to age-related hearing loss for the first time.
Identifying Slc4a10 and other genes related to late-onset conditions in mice could now prompt investigation of the same genes in humans to ask if naturally-occurring mutations in them cause similar effects.
“Our study is an important springboard for a better understanding of which genes in humans are involved in age-related conditions, and how changes in those genes influence this,” said study first author Dr. Paul Potter, of MRC Harwell Institute.
“This is a first and vital step in developing new therapies.”
“As we get older, we have an increased risk of developing many conditions, including diabetes, cardiovascular disease, hearing loss and dementia,” said Dr. Lindsay Wilson, Program Manager for Genetics and Genomics at the MRC, who was not involved in the study.
“The genes that we carry can influence this, but it is hard to know which do, or how.”
“This study increases our understanding of the genes related to ageing and ill-health and may ultimately help us to identify new treatments.”
The team’s findings were published in the August 18 issue of the journal Nature Communications.
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Paul K. Potter et al. 2016. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease. Nature Communications 7, article number: 12444; doi: 10.1038/ncomms12444
