Navigation Links
Genomic detectives crack the case of the missing heritability
Date:2/22/2013

Despite years of research, the genetic factors behind many human diseases and characteristics remain unknown. The inability to find the complete genetic causes of family traits such as height or the risk of type 2 diabetes has been called the "missing heritability" problem.

A new study by Princeton University researchers, however, suggests that missing heritability may not be missing after all at least not in yeast cells, which the researchers used as a model for studying the problem. Published in the journal Nature, the results suggest that heritability in humans may be hidden due only to the limitations of modern research tools, but could be discovered if scientists know where (and how) to look.

[Images can be seen at http://www.princeton.edu/main/news/archive/S36/13/86G93. To obtain high-res images, contact Princeton science writer Morgan Kelly, (609) 258-5729, mgnkelly@princeton.edu]

"The message of our study is that if you look hard enough you will find the missing heritability," said the senior researcher, Leonid Kruglyak, Princeton's William R. Harman '63 and Mary-Love Harman Professor in Genomics and a Howard Hughes Medical Institute Investigator. Kruglyak worked with first author Joshua Bloom, a Princeton graduate student; Wesley Loo, a 2010 Princeton graduate now a graduate student at Harvard University; Thuy-Lan Lite, Class of 2012, who is working at the National Institutes of Health for a year before starting graduate school; and Ian Ehrenreich, a past Princeton postdoctoral researcher now at the University of Southern California.

"We don't think there is some fundamental limitation such as that there are things we don't understand about how genes behave that is holding us back," Kruglyak said. "Instead, we should be able to detect the heritability in humans if we use the right tools."

Passed down from parent to child, genes determine not only eye color and other physical characteristics but also the risk of diseases. Some inherited diseases are caused by a mutation in a single gene. These single-gene disorders have well-defined patterns of inheritance that can be used to predict the chances that an individual will inherit the disease.

However, many diseases and physical traits arise due to multiple genes, multiple locations within genes, and even the regions of DNA between genes. Across the genome which is an individual's total genetic content small variations in DNA code can, when added together, increase or decrease the likelihood that a person will develop a disease or characteristic.

Height, for example, results from variations in DNA at multiple locations on the genome. Researchers have detected about 180 locations in the human genome where small alterations in the DNA code can have an influence on how tall or short a person is. Nonetheless, these locations account for only 13 percent of the expected contribution genetic code has on a person's height.

Type 2 diabetes also has missing heritability: About 40 identified genome locations are associated with the risk of developing the condition, but those account for only 10 percent of the estimated genetic influence. Finding the missing heritability for diseases like type 2 diabetes, Crohn's disease and schizophrenia could help inform prevention and treatment strategies.

In the present study, the researchers scanned the genomes of yeast cells for DNA variations which can be thought of as spelling errors in the four-letter DNA code and then matched those variations with qualities or characteristics inherited from the cells' parents. This type of study, known as a genome-wide association study (GWAS), is a common tool for searching for diseases and traits associated with variations in the genome. The researchers detected numerous DNA variations that, when added together, accounted for almost all of the offsprings' inherited characteristics, indicating that there was very little missing heritability in yeast.

Although the search for heritability was successful in yeast, finding missing heritability in humans is far more complicated, Kruglyak said. For example, interactions between genes can contribute to heritable traits, but such interactions are difficult to detect with genome-wide association studies (GWAS), which are the primary means by which geneticists look for DNA variations associated with diseases or traits. In addition, environmental factors such as nutrition also can influence gene activity, and these influences can be elusive to the genome-wide study. GWAS also may be inadequate at detecting common DNA spelling errors that have only small effects, or it may fail to find DNA variations that have a large effect but are rare.

The study sheds light on the role of nature (genetic factors) versus nurture (environmental factors) in determining traits and disease risk, according to Bert Vogelstein, director of the Ludwig Center at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute Investigator.

"The nature versus nurture argument has been brewing for decades, both among scientists and the lay public, and 'missing heritability' has been problematic for the 'nature' component," said Vogelstein, who was not involved in the Princeton study.

"This beautiful study demonstrates that the genetic basis for heritability (nature) can be precisely defined if extensive, well-controlled experiments can be performed," Vogelstein said. "Though the results were obtained in a model organism, I would be surprised if they didn't apply, at least in part, to higher organisms, including humans."

Kruglyak said that one approach to finding the missing heritability in humans might be to apply genome-wide scans to large families, rather than focusing on large populations as is currently done. Family studies take advantage of the fact that the same genetic variations will be more common in families and thus easier to detect. However, the disadvantage of family studies is that the detected genetic variations may not be widespread in the population.

For the study in yeast, the team examined the offspring of two yeast cells, one that is commonly used in laboratory studies and the other in wine making. Although yeast usually reproduce asexually, under certain conditions, such as lack of food, two yeast cells will mate and produce offspring that, like human children, receive roughly half their genetic material from each parent. "Our study involves thousands of 'kids' from a single set of parents," Kruglyak said.

The team first sequenced the genomes of the two parent cells and then conducted scans for DNA variations in the genomes of 1,008 offspring. Yeast do not inherit height or disease risk from their parents, but they can inherit the ability to survive in adverse conditions. The researchers tested the parents and their offspring for the ability to grow under various conditions, including different temperatures, acidity levels, food sources, antibiotics, metal compounds, and in drugs such as caffeine.

The researchers then looked for associations between the DNA variations inherited from the parents and growth ability, and determined that the DNA variations accounted for nearly all of the resilience noted in the offspring.


'/>"/>

Contact: Morgan Kelly
mgnkelly@princeton.edu
609-258-5729
Princeton University
Source:Eurekalert  

Related medicine news :

1. Following the genomic pathways to stop the spread of cancer
2. Genomic study of rare childrens cancer yields possible prognostic tool
3. Mayo, UCSF team discovers genomic variant that increases risk of brain tumors
4. Study identifies genes associated with genomic expansions that cause disease
5. $8.9 million NIH grant to study genomic link to premature heart disease
6. Edith Sanford Breast Cancer Foundation and TSRI partner in genomic breast cancer research
7. Molecular Genetics & Genomic Medicine: New open access journal launched by Wiley
8. Ontario Genomics Institute invests in stem cell technology at Tissue Regenerative Therapeutics
9. Study shows large-scale genomic testing feasible, impacts therapy
10. Stanford/Yale study gives insight into subtle genomic differences among our own cells
11. NIH grant moves pathologists to the forefront of genomic medicine
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Genomic detectives crack the case of the missing heritability
(Date:3/28/2017)... ... 28, 2017 , ... Award-winning medical group Allied Anesthesia today ... board chair for Orange County health care system CalOptima Friday. CalOptima announced its ... chair Mark Refowitz’s term, which runs through June 30 of this year, until ...
(Date:3/28/2017)... ... March 28, 2017 , ... In its ... Success website has recently developed and published an informational resource that addresses frequently ... based on common inquiries the site’s team of third party administrator (TPA) contributors ...
(Date:3/28/2017)... Monica, CA (PRWEB) , ... March 28, 2017 ... ... Dr. Carson Liu of SkyLex Advanced Surgical, Inc. is thrilled to offer the ... gastric balloon procedure, and this procedure adds to SkyLex Advanced Surgical’s already ...
(Date:3/28/2017)... ... 2017 , ... Oily skin is a common and unwelcomed occurrence in people of all ages, ... to offer to the discussion of dealing with excess skin oil. “Oily skin is a ... remedies that can help remove the oily shine while keeping the skin fresh and clean,” ...
(Date:3/27/2017)... (PRWEB) , ... March 27, 2017 , ... New patients ... Braasch for leading sleep apnea treatment, with or without a referral. Sleep apnea is ... which can include daytime sleepiness, morning headaches and chronic snoring. , Dr. Braasch ...
Breaking Medicine News(10 mins):
(Date:3/27/2017)... Calif. , March 27, 2017  Cryoport, Inc. ... that it intends to offer shares of common stock ... registration statement on file with the Securities and Exchange ... and other conditions, and there can be no assurance ... completed, or as to the actual size or terms ...
(Date:3/27/2017)... N.Y. , March 27, 2017 To mark ... U.S.A. , Inc., a leader in digital imaging solutions, ... Expo East convention, held at New York,s ... 2017. Save Your Vision Month, sponsored by the American Optometric ... and the importance of receiving comprehensive eye exams. In recognition ...
(Date:3/27/2017)... and VANCOUVER, British Columbia, March 27, 2017 /PRNewswire/ ... (the "Company" or "Sophiris"), a clinical late-stage biopharmaceutical ... patients with urological diseases, today reported fourth quarter ... corporate highlights. Key Corporate Highlights: ... Development for Localized Prostate Cancer. During 2016, the ...
Breaking Medicine Technology: