Nav: Home

Stepping up the hunt for genetic diseases

February 16, 2017

When a child is conceived, he or she receives DNA from both parents. The child's own genome thus consists of a maternal and a paternal genome. However, some genes -- about 100 out of the 20,000 encoded genes-- are exclusively expressed either from the maternal or from the paternal genome, with the other copy of the gene remaining silent. We know that these imprinted genes are more likely to lead to serious genetic diseases, such as Prader-Willi or Angelman syndrome. Researchers at the University of Geneva (UNIGE), Switzerland, have devised a new technique, based on a combination of biology and bioinformatics, to quickly and accurately detect the imprinted genes expressed in each of the cell types that constitute the human organs. This major breakthrough will improve our understanding and diagnosis of genetic diseases. The study can be read in full in the American Journal of Human Genetics.

The research team, led by Professor Stylianos Antonarakis from the Department of Genetic Medicine and Development in the Faculty of Medicine at UNIGE, focused on genomic imprinting. This is a set of genes exclusively expressed from the genetic code inherited either from the father (the paternal allele) or from the mother (maternal allele). Why is there so much interest in the identification of the imprinted genes? Because if a deleterious mutation affects the functional allele, it cannot be compensated by the expression of the second silent allele, likely causing a serious genetic disease. The goal, therefore, is to determine the imprinted genes in all cell types of human body tissues that are liable to cause these kind of diseases.

Until recently, millions of cells were analysed together without distinction. «We have now developed a new technique with a better resolution, known as Human Single-Cell Allele-Specific Gene Expression," explains Christelle Borel, UNIGE researcher. "The process can be used to simultaneously examine the expression of the two alleles, paternal and maternal, of all known genes in each individual cell. The method is fast and can be carried out on thousands of single cells with the utmost precision using next-generation sequencing technology." The heterogeneity of each tissue of the body is thus analysed in detail while searching for imprinted genes in disease-relevant tissue. The individual's genome is sequenced, as is the genome of both parents, in order to identify the parental origin of the alleles transcribed in the person's single cell.

Each cell is unique

Federico Santoni, first author of the study and researcher at UNIGE and HUG (Geneva University Hospitals) further explains, "We establish the profile of the allelic expression for thousands of genes in each single cell. We then process this data with a novel computational and statistical framework to identify the specific signature of each imprinted gene, enabling us to accurately record them." This new technique redefines the landscape of imprinted genes by examining all cell types, and can be applied to all tissues affected by diseases, such as cardiac and brain tissue. Moreover, the scientists have discovered novel imprinted genes and demonstrated that some were restricted to certain tissues or cell types.

This technique focuses on the specific characteristics of each individual by treating each cell as a single entity. This concept, called Single-cell Genomics, is part of an emerging field that is assuming an all-important role at UNIGE, which sees it as the future of medicine that will be personalised rather than generalised. Thanks to the technique pioneered by UNIGE researchers, it will be possible to identify new disease causing genes and to adapt a specific and targeted treatment for individual patients.
-end-


Université de Genève

Related Genome Articles:

A close look into the barley genome
An international consortium, with the participation of the Helmholtz Zentrum München, Plant Genome and Systems Biology Department (PGSB), has published methodologically significant data on the barley genome.
Barley genome sequenced
Looking for a better beer or single malt Scotch whiskey?
From Genome Research: Pathogen demonstrates genome flexibility in cystic fibrosis
Chronic lung infections can be devastating for patients with cystic fibrosis (CF), and infection by Burkholderia cenocepacia, one of the most common species found in cystic fibrosis patients, is often antibiotic resistant.
A three-dimensional map of the genome
Cells face a daunting task. They have to neatly pack a several meter-long thread of genetic material into a nucleus that measures only five micrometers across.
Rhino genome results
A study by San Diego Zoo Global reveals that the prospects for recovery of the critically endangered northern white rhinoceros -- of which only three individuals remain -- will reside with the genetic resources that have been banked at San Diego Zoo Global's Frozen Zoo®.
Science and legal experts debate future uses and impact of human genome editing in Gender & the Genome
Precise, economical genome editing tools such as CRISPR have made it possible to make targeted changes in genes, which could be applied to human embryos to correct mutations, prevent disease, or alter traits.
Genome: It's all about architecture
How do pathogens such as bacteria or parasites manage to hide from their host's immune system?
Accelerating genome analysis
An international team of scientists, led by researchers from A*STAR's Genome Institute of Singapore and the Bioinformatics Institute, have developed SIFT 4G (SIFT for Genomes) -- a software that can lead to faster genome analysis.
Packaging and unpacking of the genome
Single-cell techniques have been used to investigate histone replacement and chromatin remodeling in developing oocytes.
The astounding genome of the dinoflagellate
Dinoflagellates live free-floating in the ocean or symbiotically with corals, serving up -- or as -- lunch to a host of mollusks, tiny fish and coral species.

Related Genome Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".