Navigation Links
Infused spleen cells found not to impact islet recovery and reversal of type 1 diabetes in mice

Researchers at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins have invented a cost-effective and highly efficient way of analyzing what many have termed "junk" DNA and identified regions critical for controlling gene function. And they have found that these control regions from different species don't have to look alike to work alike.

The study will be published online at Science Express March 23.

The researchers developed a new system that uses zebrafish to test mammalian DNA and identify DNA sequences, known as enhancers, involved in turning on a gene. In studying RET, the major gene implicated in Hirschsprung disease and multiple endocrine neoplasia (MEN2), the team identified DNA sequences that can control RET but had not been identified using standard methods. Hirschsprung disease, also known as congenital megacolon, is a relatively common birth defect marked by bowel obstruction. MEN2 is an inherited predisposition to neuroendocrine cancers.

The notion that mutations in enhancers play a role in human disease progression has been difficult to confirm because usually enhancers are located in the 98 percent of the human genome that does not code for protein, termed non-coding DNA. Unlike DNA sequences that code for protein, non-coding DNA, sometimes referred to as "junk" DNA, follows few rules for organization and sequence patterns and therefore is more difficult to study.

"The difficulty with human genetic approaches to common disease is that we lack the power to precisely localize DNA sequences that are associated with disease, often leaving us immense stretches of DNA to look at," says one of the study's corresponding authors, Andy McCallion, Ph.D., an assistant professor in the McKusick-Nathans Institute. Most often one is limited to looking in the most obvious places, which may not yield the best results. "Until now," he says, "we've only been able to look under the lamplights for the car keys."

Tra ditionally, DNA sequences are thought to have to look similar to function similarly; this is how scientists identify genes in other species, a strategy best used for studying similar species. From an evolutionary standpoint, the last common ancestor of human and zebrafish lived more than 300 million years ago. Because DNA sequences in each species have changed over time, traditional methods of comparing DNA sequences between humans and zebrafish have failed to identify any potential enhancers around the RET gene because the DNA sequences differ too much.

That drove the Hopkins researchers to seek and develop this new system, by which virtually any DNA sequence can be tested for its ability to turn on a marker gene in zebrafish embryos. The system is a significant advance over current methods in this model species, allowing researchers to study more sequences in a shorter period of time. Using this, they identified several human enhancers able to control expression consistent with the zebrafish ret gene.

Zebrafish have become the ideal system for doing these types of large scale studies. They are small - only about a half inch in length - they grow quickly, and are relatively inexpensive to maintain compared to mice or rats. "Zebrafish are the only vertebrate embryo you can even think about doing this type of work in," says Shannon Fisher, M.D., Ph.D., the study's first author and an assistant professor in cell biology in Johns Hopkins' Institute for Basic Biomedical Sciences.

The researchers' next steps are further study of the RET enhancers they found to identify other mutations that might contribute to Hirschsprung disease and MEN2, and to entice other investigators to collectively build a database of human enhancers. "If there's one thing we've learned here, it's that we are not very good at recognizing enhancers. We just don't know what they look like," says Fisher. "We are anxious for others to use this technology on their favorite gen es."


'"/>

Source:Joslin Diabetes Center


Related biology news :

1. Wisconsin scientists grow critical nerve cells
2. Spleen may be source of versatile stem cells
3. Researchers discover way to make cells in the eye sensitive to light
4. Priming embryonic stem cells to fulfill their promise
5. Lack of enzyme turns fat cells into fat burners
6. Poor prenatal nutrition permanently damages function of insulin-producing cells in the pancreas
7. Elusive HIV shape change revealed; Key clue to how virus infects cells
8. Mouse brain cells rapidly recover after Alzheimers plaques are cleared
9. Enzyme allows B cells to resist death, leading to leukemia
10. Scientists rid stem cell culture of key animal cells
11. Genetically modified natural killer immune cells attack, kill leukemia cells
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/21/2017)... N.Y. and PORTLAND, Ore. ... ) and the Avamere Family of Companies (Avamere Health ... today announced a six-month research study that will apply ... improve eldercare at senior living and health centers. By ... Avamere hopes to gain insights into physical and environmental ...
(Date:2/13/2017)... 13, 2017 Former 9/11 Commission border counsel ... Janice Kephart of Identity Strategy Partners, LLP, ... Trump,s "Executive Order: Protecting the Nation From Foreign ... "As President Trump,s ,Travel Ban, Executive Order ... essentially banned the travel ban, it is important that ...
(Date:2/8/2017)... , Feb. 7, 2017 Report Highlights ... The global ... reach $11.4 billion by 2021, growing at a compound annual ... - An overview of the global markets for synthetic biology. ... estimates for 2016, and projections of compound annual growth rates ...
Breaking Biology News(10 mins):
(Date:2/23/2017)... upscale Capitol Hill neighborhood, with its swanky shops, parks and cafés, ... treatment salon to set up shop. But there,s Hair ... bistro on E Madison Ave, and CEO Maria Botham ... clinic, we pride ourselves on being a destination for parents ... stigma associated with lice. Everyone can get lice – it ...
(Date:2/23/2017)... ... February 23, 2017 , ... ... evaluation of multiple immunoassay-based threat detection technologies by researchers from the Pacific ... biosensor threat detection technology was found to have the best level of ...
(Date:2/23/2017)... ... ... The Greater Gift Initiative, Inc , (GGI) a Winston-Salem, NC 501(c)3 non-profit, ... is to advance global health and highlight the greater good of clinical trial participation ... trial volunteer. The vision of GGI is to serve as a philanthropic connector between ...
(Date:2/23/2017)... SAN FRANCISCO , Feb. 23, 2017 ... company, and Beyond Type 1, a not-for-profit advocacy and ... today announced a grant from Beyond Type 1 to ... type 1 and other insulin-requiring diabetes.  ... innovative stem cell-derived cell replacement therapies with a focus ...
Breaking Biology Technology: