Each cell in our bodies holds two metres of DNA that contains the six billion bits of the DNA code necessary for making a healthy human body. This is known as the human genome. It is now accepted that what makes people different, and contributes to their susceptibility to ill health, are the 6-10 million DNA differences in the human genome known to exist within the general population.
A surprising fact is that only 1.7% of these 6 billion bits of code represent the genes that make proteins. Proteins are the physical building blocks of our bodies and are essential to keep us healthy.
Though huge strides have been made in mapping the DNA differences associated with mental health conditions such as depression, schizophrenia and chronic anxiety thanks to the sequencing of the human genome, what surprised many was the discovery that over 98% of these DNA changes lay within the dark and mysterious remainder of the human genome that did not make protein.
This part of the genome had been largely dismissed as the junk genome but, because of its importance to health, is now known as the non-coding genome. Critically, we dont yet fully understand what type of information is contained in the non-coding genome that is so essential for human health and how DNA differences change this information result in ill-health.
To understand how the non-coding genome supports health it may be helpful to think of the human body as a vast and extremely complex community of different cells. Which means the identity of a cell, and its ability to communicate effectively with other cells, is essential for normal human development and health.
Based on this assumption, many scientists have suggested that although genes contain the information to make cells, the information required to allow these cells to communicate and organise into tissues resides in the non-coding genome. Incredibly, recent estimates suggest that the human non-coding genome contains over five times more information critical to health than that which is contained within genes.
We now know that much of the information in the non-coding genome is in the form of gene switch sequences (also known as promoters and enhancers) that control the levels that genes are turned on in specific cells and in response to specific signals. It is highly likely that these switches, by responding to signals travelling between cells, are responsible for coordinating the cell-to-cell interactions required to form the structure and function of organs such as the brain.
However, identifying these switches and their function in specific cells has been challenging. Being able to easily identify and understand these gene switches, and the effects of ill-health-inducing DNA differences on their activity, will be critical to fully understanding the genetic basis of mental health.
It has been known for some time that a number of genes are responsible for regulating behaviours such as alcohol intake and mood. Disappointingly, analysis of these genes in the human population has failed to identify changes in the DNA of these genes that were strongly associated with disorders such as alcohol abuse and chronic anxiety.
Working in collaboration with Andrew McIntosh at the University of Edinburgh, our research looked to determine what controlled the very specific expression of neuropeptides (chemical signals) in parts of the brain where they are essential to controlling normal mood and alcohol intake.
We noticed that the specific cell types in which many of these genes were switched on were shared by many different species. For example, the gene that produces the alcohol intake and mood-controlling galanin peptide was turned on in very specific regions of the hypothalamus and amygdala parts of the brain that control appetite and mood in mice, rats and humans.
We reasoned that the sequences of the gene switches that controlled this expression would also be very similar between these species. So we used powerful computers that lined up the DNA sequences of more than 100 vertebrate species and found that a non-protein-coding DNA sequence, next to the galanin gene, had changed very little through evolution, suggesting its importance for survival.
Using CRISPR genome editing, a process that allows us to make targeted deletions in the DNA of mice, we deleted this sequence from the mouse genome and found that the galanin gene was switched off in these mice. Surprisingly, we also found that mice lacking this switch drank less ethanol and that male mice had reduced fear. The most important observation was that the switch contained DNA differences in the human population that altered its activity.
Our research showed that one of the differences could be linked to alcohol abuse and anxiety in men in the UK Biobank human genetic cohort which mirrored our observations in mice. This study was recently published in the academic journal Molecular Psychiatry.
We believe that our ability to quickly and accurately identify the functional components of the non-coding human genome, and how they can go wrong to contribute to susceptibility to mental health conditions, is just the tip of the iceberg in terms of human health. Which means the same principles used in our studies can be applied for other diseases such as cancer, cardiovascular disease, Type 2 diabetes and susceptibility to Covid-19.
There is even evidence that the activity of these gene switches can be affected by life events such as childhood deprivation known to affect disease susceptibility through an epigenetic process known as DNA-methylation epigenetics being the study of biological mechanisms that switch genes on and off.
There has never been a more exciting time to be in genetics and it is hoped that the exploration of the dark matter of the non-coding genome will bring tremendous benefits in terms of being able to diagnose susceptibilities to mental health disorders and other conditions and help us develop new, more personalised treatments.
Read more:
- Study Identifies Breast Cancer Risk and Disease-Causing Mutations in Women Over 65 - Cancer Network - November 28th, 2020
- Scientists say West Africans originally migrated to East Africa - Quartz Africa - November 28th, 2020
- Major new study unveils complexity and vast diversity of Africa's genetic variation - The Conversation CA - November 28th, 2020
- Future Visioning the Role of CRISPR Gene Editing: Navigating Law and Ethics to Regenerate Health and Cure Disease - IPWatchdog.com - November 28th, 2020
- Future Visioning The Role Of CRISPR Gene Editing: Navigating Law And Ethics To Regenerate Health And Cure Disease - Technology - United States -... - November 28th, 2020
- Understanding the immunology of COVID-19 - SelectScience - November 28th, 2020
- Scientists successfully implanted human genes into monkeys to increase their brain mass - Boing Boing - November 28th, 2020
- Thirteen TUM researchers among the most cited worldwide - India Education Diary - November 28th, 2020
- Twist Bioscience Reports Fourth Quarter and Full Year Fiscal 2020 Financial Results - Business Wire - November 28th, 2020
- Spaceflight does some weird things to astronauts bodies - MIT Technology Review - November 28th, 2020
- Amgen To Present At The Evercore ISI Virtual HealthCONx Conference - GuruFocus.com - November 28th, 2020
- How to use precision medicine to personalize COVID-19 treatment according to the patients genes - TheStreet - September 2nd, 2020
- Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility - Science Advances - September 2nd, 2020
- Thought to Be Extinct, New Guinea's Singing Dogs Found Alive in the Wild - Smithsonian Magazine - September 2nd, 2020
- Humans have had mystery DNA for 300,000 yearsand now we might finally know what it is - SYFY WIRE - August 10th, 2020
- The Secret to a Long, Healthy Life Is in the Genes of the Oldest Humans Alive - Singularity Hub - August 10th, 2020
- LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business UpdatesFDA Clears IND Application for LB-001 for the... - August 10th, 2020
- Research on Tasmanian devil offers new insights into tackling human cancer - National Science Foundation - August 10th, 2020
- Human Genetics Market 2020 Size by Product Analysis, Application, End-Users, Regional Outlook, Competitive Strategies and Forecast to 2027 - Owned - August 10th, 2020
- University of Texas researchers find mutation that led to 2015-2016 Zika outbreak - Homeland Preparedness News - August 10th, 2020
- Blood lipid levels may be altered in some autistic people - Spectrum - August 10th, 2020
- NIH taps Dr. Lindsey Criswell as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases - National Institutes of Health - August 10th, 2020
- 'Hyper urban' coyote genomes are growing apart from their city and rural cousins - Massive Science - August 10th, 2020
- Why scientists are worried about a 'Warp Speed' COVID-19 vaccine - New Haven Register - August 10th, 2020
- Gyroscope Announces Appointment of Leaders in Retinal Disease, Gene Therapy and the Complement System to Its Clinical and Scientific Advisory Boards -... - August 10th, 2020
- Noel Rose, Who Demonstrated Autoimmunity Exists, Dies at 92 - The Scientist - August 10th, 2020
- Invasion of the Body Snatchers: Viruses Can Steal Our Genetic Code to Create New Human-Virus Genes - SciTechDaily - August 10th, 2020
- Why Are Only 10% of People Left-Handed? Here's What Scientists Know So Far - ScienceAlert - August 10th, 2020
- Holder pasteurization of donated human milk is effective in inactivating SARS-CoV-2 - CMAJ - August 10th, 2020
- Dinosaur diagnosed with bone cancer that afflicts humans today - CNN - August 10th, 2020
- LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business Updates - GlobeNewswire - August 10th, 2020
- The Secret to Healthy Longevity Is in the Genes of the Oldest Humans Alive - Singularity Hub - August 10th, 2020
- BU's COVID-19 Testing Passes Its First Test | BU Today - BU Today - August 10th, 2020
- COVID-19 in Africa: Dampening the storm? - Science - August 10th, 2020
- Pacific Biosciences and Asuragen Collaborate to Develop Assays for Carrier Screening and other Applications Based on SMRT Sequencing Technology and... - August 10th, 2020
- U of T researchers identify molecular switch allowing parasites to survive inside hosts without oxygen - News@UofT - August 9th, 2020
- LUMINEX : MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-Q) - marketscreener.com - August 8th, 2020
- Gaucher Disease Treatment Market Size, Top Companies, Trends, Growth Factors Details by Regions, Types and Applications - Owned - August 8th, 2020
- How studying genetics and lifestyle can shape a healthier MENA region - The European Sting - August 8th, 2020
- Detection of H1 Swine Influenza A Virus Antibodies in Human Serum Samples by Age Group - CDC - August 7th, 2020
- UW researchers devise approach to treat rare, incurable form of blindness - University of Wisconsin-Madison - August 7th, 2020
- Prevail Therapeutics to Present at 2020 Wedbush PacGrow Healthcare Conference - Stockhouse - August 7th, 2020
- human genetics | Description, Chromosomes, & Inheritance ... - August 6th, 2020
- Human Genetics | Pitt Public Health | University of Pittsburgh - August 6th, 2020
- Triplet Therapeutics To Present at Upcoming Events - Business Wire - August 5th, 2020
- 'Hyper urban' coyote genomes are growing apart their from city and rural cousins - Massive Science - August 5th, 2020
- Baylor genomics teams partner to provide COVID-19 testing for Houston area - Baylor College of Medicine News - August 5th, 2020
- Gaucher Disease Treatment Market (Impact of COVID-19) Top Growing Companies: Acetelion Pharmaceutical (J&J Ltd.), Erad Therapeutic Inc., JCR... - August 5th, 2020
- High-fat Diet and Genetics Lead to Anxiety and Depression in Rats - Newswise - August 5th, 2020
- 'Mono' virus turns on cancer-related genes. Here's how. - Live Science - August 4th, 2020
- Human Challenge Trial Neither Essential Nor Ethically Justified at This Time, Says US Expert Anthony Fauci - Yahoo India News - August 4th, 2020
- ICMR to host global web conference on science, ethics of COVID-19 vaccine starting 4.30 pm today - Firstpost - August 4th, 2020
- Faculty/staff honors: Women in engineering network nod, winning magazine article on geologic hazards and refugees and two national genetics society... - July 31st, 2020
- ENCODE3: Interpreting the human and mouse genomes - Science Codex - July 31st, 2020
- Revealing the intrinsic functioning of human and mouse genomes - Tech Explorist - July 31st, 2020
- Maternal Immune Activation Causes Schizophrenia-like Behaviors in the Offspring through Activation of Immune-Inflammatory, Oxidative and Apoptotic... - July 31st, 2020
- Podcast: The ancient war between genes and disease - Genetic Literacy Project - July 31st, 2020
- Pitt's School of Public Health welcomes students with opera about obstetrician who championed hand-washing - TribLIVE - July 31st, 2020
- BNGO Stock Price: BioNano Genomics Inc. retreats, starts week in the red - FXStreet - July 31st, 2020
- A Genetic Mutation Reveals How the SARS-CoV-2 Virus Strikes - Technology Networks - July 31st, 2020
- 88-Year Old Daniel Smith, Son Of Slave, Tells His Story - Moguldom - July 31st, 2020
- 23andMe Releases Devastating Analysis of Trans-Atlantic Slave Trade - Futurism - July 31st, 2020
- MSU researcher earns grant to study effects of droughts - MSUToday - July 31st, 2020
- Massive Growth in Human Genetics Market Breaking new grounds and touch new level in Upcoming Year by QIAGEN, Agilent Technologies, Thermo Fisher... - July 30th, 2020
- CEO of genome analysis firm: We have the data to prove people will take care of themselves - University of Miami - July 30th, 2020
- Researchers from U of T, Harvard study collective human behaviour amid COVID-19 - News@UofT - July 30th, 2020
- Gene mutations discovered as a trigger for male infertility - BioNews - July 29th, 2020
- Cerevel Therapeutics and Cyclica Announce Research Collaboration to Use Artificial Intelligence to Accelerate Discovery of Novel Medicines in... - July 29th, 2020
- Relatives of coronavirus may have been in bats for decades - Opelika Auburn News - July 29th, 2020
- Link between platelets and Covid-19 virus? - The New Indian Express - July 29th, 2020
- Fortress Biotech Announces Publication of Study on Targeted Next Generation Sequencing for Newborn Screening of Menkes Disease in Molecular Genetics... - July 29th, 2020
- New 23andMe Study Reveals the Genetic Legacy of Slavery in the Americas - Gizmodo - July 29th, 2020
- The Groundbreaking Scientist Who Risked All in Pursuit of His Beliefs - The New York Times - July 29th, 2020
- 23andMe and GSK Head to Clinical Trials With Cancer Drug - MSN Money - July 29th, 2020
- Human Genetics - David Geffen School of Medicine at UCLA - July 29th, 2020
- Prevail Therapeutics Granted Composition of Matter Patent for Experimental Gene Therapy Program PR006 - GlobeNewswire - July 29th, 2020
- The toll of shrinking jaws on human health | Stanford News - Stanford University News - July 28th, 2020
- Global Hereditary Genetic Testing Market (2020 to 2030) - Analysis and Forecast - GlobeNewswire - July 28th, 2020
- Triplet Therapeutics nabs Scholar Rock R&D exec as new CSO - FierceBiotech - July 27th, 2020
- Meet Dr Sarah Gilbert, one of the scientists leading the race to find a coronavirus vaccine - The Indian Express - July 27th, 2020