Research sheds new light on heritability of disease

January 16, 2014, Hebrew SeniorLife Institute for Aging Research

A group of international researchers, led by a research fellow in the Harvard Medical School-affiliated Institute for Aging Research at Hebrew SeniorLife, published a paper today in Cell describing a study aimed at better understanding how inherited genetic differences, or variants, predispose certain individuals to develop diseases such as type 2 diabetes. The study integrated computational methodology with experimentation to address and prove underlying genetic causes of type 2 diabetes. In principle, the new methodology can be applied to any common disease, including osteoporosis, Alzheimer's disease and cancer. The hope is that with better understanding of how DNA functions in these individuals, new treatments will follow.

Since completion of the Human Genome Project in 2003, researchers have been working to discover how genes contribute to disease. The question remains why some individuals are more at risk than others to develop certain diseases when factors such as age, gender and life-style are equal.

A small percentage of DNA contain the coded sequence that produces proteins necessary for cell growth and function. However DNA that lies outside of these coding regions play an essential role in turning genes on and off. By understanding how these work in concert with one another, we may identify targets for future therapies.

The method developed and tested by this study tracks patterns within regulatory regions in a number of species close or distant to humans. If a pattern of variants in these non-coding regions is present in many species, it is likely to serve a very important function.

According to study co-author and Institute Fellow, Melina Claussnitzer, Ph.D., "It has become clear that the bulk of disease associated variants are located in the non-coding part of the DNA, where the function of the DNA is largely unknown. Non-coding variants are known to contribute to disease through dysregulation of . But pinpointing the non-coding variants, which confer this dysregulation remains a major challenge."

The authors applied the analysis to genetic variants associated with , one of the most prevalent human diseases. The integration of their computational approach together with several experimental approaches (thereby addressing and proving causality) identified a 2 diabetes variant that promotes disease by interfering with gene regulation and altering fat cell function.

Instead of only considering the conservation of DNA sequences across species, the researchers' computational methodology finds conserved patterns of certain sequences that make up transcription factor binding sites (TFBS) where proteins bind to regulate gene expression. To find these conserved TFBS patterns, the computer uses data about a given region around a gene variant in the human genome, and searches for comparable regions in other vertebrate species. The TFBS pattern conservation of the regions is then scored based on the similarity of TFBS arrangement across species. A high score indicates a high probability that this variant affects the regulation of genes, thereby pointing to the underlying mechanism of a disease.

Explore further: Non-coding DNA implicated in type 2 diabetes

Related Stories

Non-coding DNA implicated in type 2 diabetes

January 12, 2014
Variations in non-coding sections of the genome might be important contributors to type 2 diabetes risk, according to a new study.

Sieving through 'junk' DNA reveals cancer-causing genetic mutations

October 3, 2013
Researchers can now identify DNA regions within non-coding DNA, the major part of the genome that is not translated into a protein, where mutations can cause diseases such as cancer.

Why is type 2 diabetes an increasing problem?

January 9, 2014
Contrary to a common belief, researchers have shown that genetic regions associated with increased risk of type 2 diabetes were unlikely to have been beneficial to people at stages through human evolution.

Methylation linked to metabolic disease

November 11, 2013
(Medical Xpress)—In the first in-depth analysis of DNA methylation in fat, a process that affects the regulation of genes, researchers have linked regions of methylation to metabolic traits such as high body mass index ...

Common disorders: It's not the genes themselves, but how they are controlled

December 20, 2013
Many rare disorders are caused by gene mutation, like sickle cell anemia. Yet until now the underlying genetic cause of more common conditions – for example, rheumatoid arthritis – has evaded scientists for years.

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.