Researchers produce a catalog of the deleterious and disease-causing genetic variants in healthy people
Researchers at Cambridge and Cardiff have found that, on average, a normal healthy person carries approximately 400 potentially damaging DNA variants and two variants known to be associated directly with disease traits. They showed that one in ten people studied is expected to develop a genetic disease as a consequence of carrying these variants.
It has been known for decades that all people carry some damaging genetic variants that appear to cause little or no ill effect. But this is the first time that researchers have been able to quantify how many such variants each of us has, and list them. This figure of 400 is likely to increase as more and more powerful genetic studies discover rare genetic variants more efficiently. Such research brings to the fore ethical questions surrounding anonymous studies and incidental findings.
"For over half a century, medical geneticists have wanted to establish the magnitude of the damage caused by harmful variants in our genomes," says Dr Yali Xue, lead author from the Wellcome Trust Sanger Institute. "Our study finally brings us closer to understanding the extent of these damaging mutations.
"We measured the number of potentially damaging variants in the genomes of apparently normal healthy humans by comparing two different datasets: whole genome sequences from 179 people in the 1000 Genomes Pilot Project, who were unlikely to have any overt genetic disease at the time of sampling, and information from the Human Gene Mutation Database (HGMD), a detailed catalogue of human disease-causing mutations that have been reported in the scientific literature."
In many cases, the disease or damaged variants were single, 'recessive' genetic variants that are unlikely to cause any harm to the carrier. A recessive genetic variant will only exert its effect when two copies – one in each chromosome – are present.
In one in ten people, however, the team could point to a potential clinical effect of the genetic variants. This is because these people either carry two copies of a specific recessive disease variant, or alternatively a dominant genetic variant. Dominant disease genetic variants can give rise to a disease trait when even a single copy is present.
"In the majority of people we found to have a potential disease-causing mutation, the genetic condition is actually quite mild, or would only become apparent in the later decades of life," says Professor David Cooper, lead author of the study from Cardiff University. "We now know that normal healthy people can possess many damaged or even completely inactivated proteins without any noticeable impact on their health. It is extremely difficult to predict the clinical consequences of a given genetic variant, but databases such as HGMD promise to come into their own as we enter the new era of personalized medicine."
Catalogues of disease-causing variants such as HGMD have been created over the past two decades but they are still far from complete. Disease variants are generally extremely rare and comprehensive searches for such mutations in many populations have scarcely begun.
The genome samples selected for this study were anonymized so the participants could not receive any information about whether or not they might be at risk for a particular genetic disorder. This is increasingly becoming an ethical issue for medical geneticists.
"Should incidental findings be fed back to people who have volunteered their sample to a study? There is no clear answer to this question," says Dr Chris Tyler-Smith, lead author from the Wellcome Trust Sanger Institute. "All of our genomes contain flaws; some of us will carry deleterious variants but will not be at risk of acquiring the associated disease for one reason or another. For others, there will be health consequences, and early warning could be useful, but might still come as an unwelcome surprise to the participant."
As DNA sequencing becomes more commonplace, geneticists must determine the most ethical way to handle this sensitive information.
More information: Yali Xue, Yuan Chen, Qasim Ayub, et al (2012). 'Deleterious- and Disease-Allele Prevalence in Healthy Individuals: Insights from Current Predictions, Mutation Databases, and Population-Scale Resequencing' Published online in American Journal of Human Genetics on 06 December. Volume: 91; Issue: 6; Manuscript: 1298.
Journal reference: American Journal of Human Genetics
Provided by Wellcome Trust Sanger Institute
- When is a gene not a gene? New catalog helps identify gene variations associated with disease Feb 16, 2012 | not rated yet | 0
- Inactive genes surprisingly common in humans Feb 16, 2012 | not rated yet | 0
- Men and women are different in terms of genetic predispositions, study shows Sep 20, 2012 | not rated yet | 0
- Study suggests rare genetic variants most likely to influence disease Mar 31, 2011 | not rated yet | 0
- Johns Hopkins to participate in 1000 Genomes Project Jan 22, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
DNA databases might help identify victims of crime and human trafficking, but how do we safeguard the personal privacy of innocent victims and family members? A new report online May 15 in the Cell Press journal Trends in ...
Genetics May 15, 2013 | not rated yet | 0
A new computer model could help scientists predict when a particular strain of avian influenza might become infectious from bird to human, according to a report to be published in the International Journal Data Mining an ...
20 minutes ago | not rated yet | 0
Researchers at Lund University in Sweden have mapped the significance of heredity for common forms of atherosclerotic disease. No studies have previously examined whether different forms of the disease share heredity.
17 minutes ago | not rated yet | 0
It is impossible to predict the evolution of China's human H7N9 bird flu outbreak as researchers are still trying to understand the source of human transmission, the head of the World Health Organisation said Monday.
27 seconds ago | not rated yet | 0
Federal health regulators say an experimental insomnia drug from Merck can help patients fall asleep, but it also carries worrisome side effects, including daytime drowsiness and suicidal thinking.
13 minutes ago | not rated yet | 0
Over the past few decades, neuroscientists have made much progress in mapping the brain by deciphering the functions of individual neurons that perform very specific tasks, such as recognizing the location ...
1 hour ago | not rated yet | 0 |
There is a link between use of anabolic-androgenic steroids and reduced mental health later in life. This is the main conclusion of a new study on elite male strength athletes that researchers from the University of Gothenburg ...
1 hour ago | not rated yet | 0