Featured Research

from universities, journals, and other organizations

Faster, Cheaper Way To Find Disease Genes In Human Genome Passes Initial Test

Date:
September 1, 2009
Source:
University of Washington
Summary:
Researchers have successfully developed a novel genomic analysis strategy for faster, cheaper discovery of gene-disease links. The strategy was tested on the genomes of unrelated individuals with the same inherited disorder. The method might be extended to common medical conditions with complex genetics by making it possible to study the genomes of large groups of people.

University of Washington (UW) researchers have successfully developed a novel genome-analysis strategy for more rapid, lower cost discovery of possible gene-disease links. By saving time and lowering expenses, the approach makes it feasible for scientists to search for disease-causing genes in people with the same inherited disorder but without any family ties to each other.

Related Articles


The strategy also might be extended to common medical conditions with complex genetics by making it more cost-effective and efficient to study the genomes of large groups of people.

Such large-scale research hasn't been undertaken because it has been prohibitively expensive, cumbersome, and time-consuming to sequence, compare and interpret entire human genomes.

The study, published August 19 in Nature by lead author Sarah B. Ng, a graduate student in the UW Department of Genome Sciences, was conducted as a proof-of-concept to see if a more targeted analysis and newer technology could identify candidate genes for Mendelian disorders. These are diseases like cystic fibrosis or sickle cell anemia that are caused by a mutation in a single gene and are passed along through generations in a simple inheritance pattern. In this study, the rare Mendelian disorder picked to evaluate the strategy in unrelated, affected individuals was Freeman-Sheldon syndrome.

The study's senior author is Jay Shendure, UW assistant professor of genome sciences. In addition to the Shendure lab, the UW labs of Deborah Nickerson, Genome Sciences; Michael Bamshad, Pediatrics; and Evan Eichler, Genome Sciences, played key roles in the collaborative study.

To make progress in disease genetics, new strategies such as this are vital. Shendure gave an example: "The genetics of thousands of rare diseases remains unsolved because sufficient numbers of families with individuals affected by those disorders are not easily available. Even with such families, mapping and identifying the causative gene can take many years."

From attempts to determine the genetics of cancer, diabetes, and heart disease, scientists now realize that common variations in the human genome account for only a small fraction of the risk of these common diseases. The new strategy allows researchers to investigate the contributions of rare variants and might be extended to larger population studies to untangle the complex genetics underlying the leading causes of death and disability.

Shendure explained the team's approach: "We decided to focus only on the 1 percent of the human genome which codes for proteins. This portion is called the exome. In other words, we determined the genetic variation in these areas, and ignored the rest. We used new technologies to capture these specific regions in the genomes of 12 people, 4 of whom were affected by the same Mendelian disorder. None of the subjects were relatives. We then decoded these selected parts of the genome through massively parallel DNA sequencing, a technology that allows one to sequence hundreds of millions of DNA fragments in parallel." Intersecting these data found that only a single gene, MYH3, contained novel mutations in the exomes of all four affected individuals.

The UW was one of three institutions, along with Harvard Medical School and the Broad Institute, funded in 2008 for The Exome Project by the National Heart, Lung and Blood Institute of the National Institutes of Health. The project aims at developing technologies to selectively sequence the human exome.

Shendure pointed out that a limitation of sequencing only exomes is that it doesn't reveal the regulatory, structural or other non-coding differences between human genomes.

Despite this limitation, genome-focused sequencing has several advantages: "Our focus on the protein-coding subset of the genome enables us do at least 20 times more samples than could be done with whole genome sequencing with equivalent effort," Shendure said. The data-gathering for this project started in November of 2008, and finished in February 2009. However, with the technical advances the researchers have achieved, a similar type of rare disease could be solved in a matter of weeks, and in the future even more rapidly.

As "second-generation" DNA sequencing technologies such as this expand in their use and overcome obstacles in the cost and time for collecting data, Shendure predicts different challenges will follow each step. For example, the amount of raw data that is collected by these sequencing instruments at the UW alone soon will be measured in petabytes. A petabyte is one quadrillion units of computer data, roughly the equivalent of 6 billion Web photos. New computational approaches for data analysis are a major part of the UW efforts, and they are expanding the new information that can be obtained with an exome-based approach.

"Massively parallel technologies that make it possible to study individual genomes have only recently emerged," Shendure said, "but hold significant promise for gaining new insights in human biology and medicine. This approach to human exome sequencing will be the key in scaling everyone's efforts to explore the genetics of both susceptibility and resistance to more complex human diseases such as heart disease, cancer, and infectious diseases."

In addition to Ng and Shendure, the research team included Emily Turner, Peggy Robertson, Steven Flygare, Choli Lee, Tristan Shaffer, Michelle Wong, Evan Eichler, and Deborah Nickerson, all from UW Genome Sciences; Abigail Bigham and Michael Bamshad from UW Pediatrics, and Arindam Bhattacharjee from Agilent Technologies.

The research was supported by grants from the National Heart, Lung, and Blood Institute, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of the National Institutes of Health; the Washington Research Foundation, and the Agency for Science, Technology, and Research in Singapore.


Story Source:

The above story is based on materials provided by University of Washington. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sarah B. Ng et al. Targeted Capture and Massively Parallel Sequencing of 12 Human Genomes. Nature, August 19, 2009

Cite This Page:

University of Washington. "Faster, Cheaper Way To Find Disease Genes In Human Genome Passes Initial Test." ScienceDaily. ScienceDaily, 1 September 2009. <www.sciencedaily.com/releases/2009/08/090817142853.htm>.
University of Washington. (2009, September 1). Faster, Cheaper Way To Find Disease Genes In Human Genome Passes Initial Test. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2009/08/090817142853.htm
University of Washington. "Faster, Cheaper Way To Find Disease Genes In Human Genome Passes Initial Test." ScienceDaily. www.sciencedaily.com/releases/2009/08/090817142853.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins