Home Features Best of 2012 Best of 2012 // #80: Common Disease from Rare Genes

Best of 2012 // #80: Common Disease from Rare Genes

Best of 2012 // #80: Common Disease from Rare Genes

Ten thousand years ago, there were only 5 million people on Earth.  That’s fewer than the current population of Singapore.  Since then, the population of the planet has soared, reaching 7.5 billion.  This drastic and sudden increase of population is having a marked effect on the human genome,  as researchers are finding large upticks in the number of very rare DNA mutations.  That finding is in turn casting doubt on the long-held belief that just a few gene mutations cause the wide variety of hereditary disease.  Researchers are beginning to suspect that those hereditary diseases are cause by a wider variety of extremely rare mutations, which can vary from one person to the next, which complicates the ability to both understand and treat them.

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For years, it has been understood that each one of our approximately 20,000 protein-coding genes coming in a variety of forms, some with major health impacts.  Recently, improved gene-sequencing technology and larger studies of populations have made it possible to detect mutations that occurs in about 1 percent of the populations.  Geneticists have long suspected even rarer mutations exists, and this year, they were proven correct.

A team at the University of Washington looked at 15,585 different genes in 2,440 different people.  They found a whopping 86 percent of the mutations were of the rarer variety – ones that were found in only 0.05 percent of the population.  Another report, published in May, saw UCLA researchers team up with GlaxoSmithKline to look at 202 genes in 14,002 people.  They found that 95 percent of the mutations were present .5 percent of the subjects, and 74 percent were found in only one or two people.  A third study from the 1,000 Genomes Projects Consortium concluded that in the average person, up to 400 of these ultra rare mutations can disrupt gene activity.

The widespread prevalence of rare and ultra rare mutations is a direct consequence of the boom in population.  Each person born acquires a few dozen mutations at birth.  Overtime, more harmful mutations are weeded out by natural selection and evolution.  Rapid population grown, however, has introduced so many new mutations that many related to disease are likely still present,

“The more individuals there are, the more mutations have arisen recently,”  –
Alon Keinan, population geneticist, Cornell University

The mere existence of so many ‘rare’ mutations also complicates the effort to study how genes and health are related.  When researching how different mutations affect lung cancer risks, for example, scientists can no long simply look at the DNA and health records of a smaller group of people; many rare mutations would be missing from such a small smaple.  Even more concerning, each disease is likely caused by a wider variety of genetic errors than previously thought, and that mix could vary widely.  A cancer patient in Canada may have a different combination of rare gene mutations contributing to cancer than a cancer patient in South Africa.

“It’s bad news for mathematically associating variants with particular complex diseases,”

It’s also bad news for using those associations to develop better drugs.  Since a single disease may result from a hundred different mutation combinations, its unlikely that researchers will find a single drug that will be effective across all patients.

However, John Novembre of UCLA points out that these ultra rare mutations will help us piece together the history of undocumented migrations and mixing of populations.  Most of the known genetic markets for ancestry are shared by tens of millions of people, which means they can only be so specific.  Using rare variety that have arisen in the past few hundreds of years means they could be limited to people from one country or region of a country.

“We can learn much more about migrations of the recent past,” Novembre says.


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