Cross-species strategy might be a powerful tool for studying human disease

February 3, 2011, Cell Press

A new study takes advantage of genetic similarities between mammals and fruit flies by coupling a complex genetic screening technique in humans with functional validation of the results in flies. The new strategy, published by Cell Press on February 3rd in The American Journal of Human Genetics, has the potential to be an effective approach for unraveling genetically complex human disorders and providing valuable insights into human disease.

Genome-wide association studies (GWASs) involve sifting through the complete set of DNA from many individuals to identify genetic variations associated with a particular disease. Although this technique has proven to be a powerful tool for developing a better understanding of diseases, such as Alzheimer's disease (AD), that involve multiple genetic variations, there are substantial limitations. Perhaps most significantly, follow-up studies aimed at validating disease-associated genetic variations in humans require large sample sizes and a great deal of effort. The current study validates GWAS results by using an inventive alternative approach.

"Simple genetic models of human disease, such as in the fruit fly, have been important experimental tools for many years, particularly for large-scale functional testing of genes," explains a senior study author, Mel B. Feany, MD, PhD, from Brigham and Women's Hospital.. "We therefore hypothesized that the fly disease model might fulfill the growing need for efficient strategies for validation of association signals identified by GWAS."

Dr. Joshua M. Shulman and colleagues implemented a two-stage strategy to enhance a GWAS of AD neuropathology by integrating the results of gene discovery in humans with functional screening in a fly model system relevant to AD biology. Specifically, the researchers evaluated 19 genes from 15 distinct genomic regions identified in a human GWAS designed to identify genes that influence AD pathology. In six out of these 15 genomic regions, a causal gene was subsequently identified in the fly disease model on the basis of interactions with the neurotoxicity of Tau protein, a well-known constituent of AD pathology.

The authors also discuss the potential for application of their technique to studies examining other human diseases. "Evidence is emerging in support of a polygenic model of inheritance for complex genetic disorders, particularly neuropsychiatric diseases, in which hundreds or even thousands of common gene variants collectively contribute to disease risk," says co-author Philip L. De Jager, MD, PhD, also of Brigham and Women's Hospital. "Our strategy of coupling human GWAS with functional in a model organism will likely be a powerful strategy for follow-up of such signals in the future in order to prioritize genes and pathways for further investigation."

Related Stories

Recommended for you

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 ...

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. ...

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 ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

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.