Featured Research

from universities, journals, and other organizations

Link Uncovered Between Variation In Humans With Extreme Body Mass And Abnormal Splicing

Date:
December 29, 2007
Source:
Cold Spring Harbor Laboratory
Summary:
Researchers report new insights into how genetic variation may create phenotypic differences between individuals. This study, which investigates the influence of mutations associated with obesity on the mechanism of splicing, is published in Genome Research.

Researchers report new insights into how genetic variation may create phenotypic differences between individuals. This study investigates the influence of mutations associated with obesity on the mechanism of splicing.

Related Articles


Many visible differences are apparent between individuals, ranging from height and weight to hair and eye color. While the extent of genetic variation between individuals is relatively small (0.1%-0.5%), it is estimated that this variation includes approximately 3 million single nucleotide polymorphisms (SNPs). These single base-pair differences in the genome have previously been thought to produce changes in the protein sequence encoded by a gene (non-synonymous SNPs). However, studies have indicated that a significant number of SNPs do not alter the predicted protein sequence (synonymous SNPs), suggesting that other regulatory mechanisms might be influenced.

In the study a research group led by Dr. Gil Ast of Tel Aviv University has analyzed a newly described dataset of SNPs found in individuals with extreme body mass index (BMI) values. Interestingly, nearly 40% of the SNPs associated with obesity do not alter the protein-coding sequence of genes.

"We demonstrated that the SNPs found in extreme BMI individuals that do not alter protein sequence information affect the way genetic information is processed: these SNPs alter mRNA splicing," explains Amir Goren, co-lead author of the study. Splicing is the process whereby the RNA transcribed from a gene is edited by linking together the protein-coding regions (exons) and removing the intervening, non-coding sequences (introns), generating a mature messenger RNA (mRNA). The translation of mRNA into functional proteins requires proper maintenance of the splicing mechanism.

Goren and colleagues find that synonymous SNPs associated with extreme BMI are located near splice sites in exons and exhibit a tendency to reside within splicing regulatory regions, suggesting that these SNPs could alter the normal splicing pattern. Furthermore, it was discovered that the exons harboring these SNPs exhibit weak splice sites, indicating that these exons could be prone to reduced frequency of splicing, potentially disrupting function of the translated protein.

"When a certain exon is added only to a fraction of the mRNA molecules and not the others, the mRNA molecules without the exon cannot support proper protein synthesis and the overall level of required protein is reduced," describes co-lead author Eddo Kim, suggesting that in addition to phenotypes attributable to non-synonymous SNPs, alterations in the processing of RNA due to synonymous SNPs could also contribute to phenotypic differences and genetic disorders.

Kim suggests that it is difficult to observe severe shifts in splicing patterns that are likely to result in lethality during development. Slight alterations in splicing are more likely to be non-fatal, yet produce a discernible phenotype. "Subtle changes in genes that are involved, for example, in metabolism of fats might be phenotypically visible later in life as unusual weight gain."

While current genetic variation databases contain millions of SNPs, most were identified from a small number of individuals, hinting that many more SNPs remain undiscovered. "Deep re-sequencing efforts could uncover many otherwise overlooked SNPs," explains Kim. "We might end up finding that SNPs that affect the splicing process explain many of the phenotypic differences between individuals."

Scientists from Tel Aviv University (Tel Aviv, Israel) and the University of California, San Francisco (San Francisco, CA) contributed to this study.

This work was supported by grants from the Israel Science Foundation, the Ber-Lehmsdorf Memorial Fund, and the Clore Scholars Programme.

Journal reference: Goren, A., Kim, E., Amit, M., Bochner, R., Lev-Maor, G., Ahituv, N., and Ast, G. 2007. Alternative approach to a heavy weight problem. Genome Res. doi:10.1101/gr.6661308.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

Cold Spring Harbor Laboratory. "Link Uncovered Between Variation In Humans With Extreme Body Mass And Abnormal Splicing." ScienceDaily. ScienceDaily, 29 December 2007. <www.sciencedaily.com/releases/2007/12/071220172139.htm>.
Cold Spring Harbor Laboratory. (2007, December 29). Link Uncovered Between Variation In Humans With Extreme Body Mass And Abnormal Splicing. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2007/12/071220172139.htm
Cold Spring Harbor Laboratory. "Link Uncovered Between Variation In Humans With Extreme Body Mass And Abnormal Splicing." ScienceDaily. www.sciencedaily.com/releases/2007/12/071220172139.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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