Navigation Links
Individual differences caused by shuffled chunks of DNA in the human genome
Date:9/27/2007

New Haven, Conn. A study by Yale researchers offers a new view of what causes the greatest genetic variability among individuals suggesting that it is due less to single point mutations than to the presence of structural changes that cause extended segments of the human genome to be missing, rearranged, or present in extra copies.

The focus for identifying genetic differences has traditionally been on point mutations or SNPs changes in single bases in individual genes, said Michael Snyder, the Cullman Professor of Molecular, Cellular & Developmental Biology and senior author of the study, which was published in Science Express. Our study shows that a considerably greater amount of variation between individuals is due to rearrangement of big chunks of DNA.

Although the original human genome sequencing effort was comprehensive, it left regions that were poorly analyzed. Recently, investigators found that even in healthy individuals, many regions in the genome show structural variation. This study was designed to fill in the gaps in the genome sequence and to create a technology to rapidly identify structural variations between genomes at very high resolution over extended regions.

We were surprised to find that structural variation is much more prevalent than we thought and that most of the variants have an ancient origin. Many of the alterations we found occurred before early human populations migrated out of Africa, said first author Jan Korbel, a postdoctoral fellow in the Department of Molecular Biophysics & Biochemistry at Yale.

To look at structural variants that were shared or different, DNA from two females one of African descent and one of European descent was analyzed using a novel DNA-based methodology called Paired-End Mapping (PEM). Researchers broke up the genome DNA into manageable-sized pieces about 3000 bases long; tagged and rescued the paired ends of the fragments; and then analyzed their sequence with a high-throughput, rapid-sequencing method developed by 454 Life Sciences.

454 Sequencing can generate hundreds of thousands of long read pairs that are unique within the human genome to quickly and accurately determine genomic variations, explained Michael Egholm, a co-author of the study and vice president of research and development at 454 Life Sciences.

Previous work, based on point mutations estimated that there is a 0.1 percent difference between individuals, while this work points to a level of variation between two- and five-times higher, said Snyder.

We also found hot spots particular regions where there is a lot of variation, said Korbel. While these regions may be still actively undergoing evolution, they are often regions associated with genetic disorder and disease.

These results will have an impact on how people study genetic effects in disease, said Alex Eckehart Urban, a graduate student in Snyders group, and one of the principal authors on the study. It was previously assumed that landmarks, like the SNPs mentioned earlier, were fairly evenly spread out in the genomes of different people. Now, when we are hunting for a disease gene, we have to take into account that structural variations can distort the map and differ between individual patients.

While it may sound like a contradiction, says Snyder, this study supports results we have previously reported about gene regulation as the primary cause of variation. Structural variation of large of spans of the genome will likely alter the regulation of individual genes within those sequences.

According to the authors, even in healthy people, there are variants in which part of a gene is deleted or sequences from two genes are fused together without destroying the cellular activity with which they are associated. They say these findings show that the parts list of the human genome may be more variable, and possibly more flexible, than previously thought.


'/>"/>

Contact: Janet Rettig Emanuel
janet.emanuel@yale.edu
203-432-2157
Yale University
Source:Eurekalert

Related biology technology :

1. Age of empowered individuals: People power behind robust computing
2. The Enterprise and the Individual
3. WTN Interview: HHS Secretary calls for $550 million health care fund to reduce deaths caused by medical errors
4. Human Primary Preadipocytes and Differentiated Adipocytes
5. Low Abundance cDNA Cloned Using Stratagenes Human Universal cDNA Library
6. Control RT-PCR Primers for Human Gene Transcripts with Varying Abundance
7. New Mammalian Expression Vectors Employ Stable, High-Level Fluorescence Humanized Renilla GFP Reporter
8. Human Universal cDNA Library Array I
9. Map and Link Human Genetic Disorders with SSLP Analysis
10. RT-PCR Primer Sets for Human and Mouse Mismatch Repair Genes
11. Transfection of Green Fluorescent Protein into Human Adrenalcarcinoma Cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/25/2016)... ... May 25, 2016 , ... ... variety of fracture-specific plating options designed to address fractures of the distal tibia ... solutions. , The Acumed Ankle Plating System 3 is composed of seven plate ...
(Date:5/25/2016)... ... 2016 , ... WEDI, the nation’s leading authority on the use of health ... has been named by the WEDI Board of Directors as WEDI’s president and CEO. ... with more than 35 years of experience in healthcare, association management and organizational leadership, ...
(Date:5/24/2016)... 24, 2016   MedyMatch Technology Ltd ., the data ... real-time decision support tools in the emergency room, announced today ... Israeli Advanced Technology Industries (IATI) BioMed Conference. ... 15th National Life Sciences and Technology Week, and is ... Hotel in Tel Aviv, Israel . ...
(Date:5/23/2016)... ... 23, 2016 , ... PrecisionAg® Media has released its latest ... The paper outlines the key trends that are creating both opportunities and challenges ... lot of highs and lows as the precision agriculture market has grown and ...
Breaking Biology Technology:
(Date:5/12/2016)... May 12, 2016 WearablesResearch.com , a ... the overview results from the Q1 wave of its ... wave was consumers, receptivity to a program where they ... a health insurance company. "We were surprised ... says Michael LaColla , CEO of Troubadour Research, ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 ... of Infosys (NYSE: INFY ), and Samsung SDS, ... partnership that will provide end customers with a more ... payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ) ... financial services, but it also plays a fundamental part in ...
(Date:4/26/2016)... , April 27, 2016 ... the  "Global Multi-modal Biometrics Market 2016-2020"  report to ... ) , The analysts forecast the ... CAGR of 15.49% during the period 2016-2020.  ... number of sectors such as the healthcare, BFSI, ...
Breaking Biology News(10 mins):