Breaking News
December 17, 2017 - New Insight on Killer Fungus Threatening Bats
December 17, 2017 - Early Atherosclerosis Defies ‘Normal’ Cholesterol
December 17, 2017 - CRF1 stress receptor is regulator of mast cell activity during stress
December 17, 2017 - CREST Failed to Dampen Enthusiasm for Carotid Stenting in Elderly
December 17, 2017 - Rising levels of HIV drug resistance
December 17, 2017 - Aging brain’s failure to coordinate deep-sleep brainwaves makes older adults forget
December 17, 2017 - Rural Workers Have Higher Exposures to COPD-Causing Pollutants
December 17, 2017 - Don’t Delay Hip Fracture Surgery. Here’s Why: MedlinePlus Health News
December 17, 2017 - NIH launches HIV prevention trial of long-acting injectable medication in women
December 17, 2017 - Op-Ed: Get Ready for a Tsunami of ECGs
December 17, 2017 - Observation care may save more than thought
December 17, 2017 - Scientists explore effectiveness of action video games to combat dyslexia
December 17, 2017 - Teens Acting Badly? Smog Could Be to Blame
December 17, 2017 - FDA Says ‘Yes’ to Short-Acting Insulin Admelog
December 17, 2017 - Vaping popular among teens; opioid misuse at historic lows
December 17, 2017 - Lower Urinary Symptoms Occur in Almost All Patients with SSc
December 17, 2017 - Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)
December 16, 2017 - Butler Hospital launches international Alzheimer’s disease prevention study
December 16, 2017 - iMedicalApps: Virtual Reality Boosts Self-Confidence for Med Students
December 16, 2017 - Researchers validate five new genes responsible for Amyotrophic Lateral Sclerosis
December 16, 2017 - New genetic analysis of candidiasis reveals surprising fungal sex secrets
December 16, 2017 - New high precision machine-learning model could help accelerate drug discovery
December 16, 2017 - Groundbreaking gene therapy trial brings cure for hemophilia closer
December 16, 2017 - Racial Differences Seen in IgG4 Disease
December 16, 2017 - Treacher Collins Syndrome
December 16, 2017 - New approach to tracking how deadly ‘superbugs’ travel could slow their spread
December 16, 2017 - Muscle paralysis may promote breakdown of bones
December 16, 2017 - WSU scientists create injectable dye to track progression of diseases
December 16, 2017 - Kaiser Permanente delivers clot-busting drugs to stroke patients more than twice as fast as national rates
December 16, 2017 - Some Great Holiday Foods for Weight Loss
December 16, 2017 - Shared Decision-Making Strategies for Lung Ca Screening Get High Marks
December 16, 2017 - Lactic acid bacteria can protect against Influenza A virus, study finds
December 16, 2017 - Cancer immunotherapy’s effectiveness may depend on patient’s genetic makeup
December 16, 2017 - Researchers explore patient-doctor conversations, best practices linked to opioid tapering
December 16, 2017 - ‘Virtual child’ to help professionals learn key techniques to treat children with autism
December 16, 2017 - IU scientists discover way to make drug treatment more successful against malaria
December 16, 2017 - Prostate cancer researchers find significant disparities between two liquid biopsy providers
December 16, 2017 - ED-Diagnosed Lung Ca Patients Worse Off: Clin Onc News Report
December 16, 2017 - Calcium in Urine Test: MedlinePlus Lab Test Information
December 16, 2017 - Pregnancy-related conditions taken together leave moms—and dads—at risk
December 16, 2017 - Research uncovers mechanism implicated in defective function of tumor-associated dendritic cells
December 16, 2017 - OncoBreak: Stubborn Racial Disparities; Paid Medical Leave & Chemo; DIY Gene Tests
December 16, 2017 - Critical link between obesity and diabetes has been identified
December 16, 2017 - Transfusion dependence reduces access to high-quality end-of-life care for leukemia patients
December 16, 2017 - Porvair and Suzhou Tianlong Bio to develop epigenetic analysis technologies
December 16, 2017 - FDA Approves Ixifi (infliximab-qbtx), a Biosimilar to Remicade
December 16, 2017 - Morning Break: Trump to Get Check-Up; Cancerous Transplant; Death Knell for MIPS?
December 16, 2017 - First transcatheter implant for diastolic heart failure successful
December 16, 2017 - ‘Sushi-like’ nanodiscs provide structural snapshots of misfolding proteins
December 16, 2017 - Inherited gene variation may be to blame for poor survival of patients with early-onset breast cancer
December 16, 2017 - Sign-up deadline is Friday, but some people may get extra time
December 16, 2017 - Higher Booze Taxes Might Pay Off for Public Health
December 16, 2017 - Regular Activity in Midlife Spares Joints in Women
December 16, 2017 - Rain May Not Cause Achy Joints After All: MedlinePlus Health News
December 16, 2017 - MedDiet adherence doesn’t affect acute heart failure mortality
December 16, 2017 - HKBU experts develop new generation of smart anti-cancer drug molecules
December 16, 2017 - Chronic Kidney Disease Audit finds wide variations in coding of CKD patients in primary care
December 16, 2017 - Scientists use nanoparticles to fight Mucoviscidosis
December 16, 2017 - Increasing physical activity decreases risk of death from lymphoma
December 16, 2017 - Fear compromises the health, well-being of immigrant families, survey finds
December 16, 2017 - Rejected antibiotic candidate could be worth a second look, research finds
December 16, 2017 - Is Nation on the Right Track to Combat Opioid Crisis?
December 16, 2017 - Arthritis No Longer Just a Disease of the Old: MedlinePlus Health News
December 16, 2017 - Study reveals biology behind why muscle stem cells respond differently to aging or injury
December 16, 2017 - Family members without inherited mutation have increased risk of melanoma
December 16, 2017 - Researchers reveal previously unknown mechanism that inhibits cells’ ability to develop into tumors
December 16, 2017 - Studies highlight potential of fMRI applications to detect, treat epilepsy in children
December 16, 2017 - Active surveillance proposed as first-line approach to manage patients with low-risk PMC of the thyroid
December 16, 2017 - Patients’ life values affect their attendance at medical treatment for pelvic-floor dysfunction
December 16, 2017 - Experts consider hazards of antibiotic resistances to be high
December 16, 2017 - Study finds erectile dysfunction as risk factor for early cardiovascular disease
December 16, 2017 - Amber-tinted glasses may reduce insomnia severity
December 16, 2017 - Arthritis Drug Seen Lowering GvHD Risk
December 16, 2017 - Atoh1, a potential Achilles’ heel of Sonic Hedgehog medulloblastoma
December 15, 2017 - Cornell engineers develop new method to measure vital signs using radio waves
December 15, 2017 - Rutgers studies highlight need for salon clients, workers to protect themselves from health risks
December 15, 2017 - FDA Approves Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
December 15, 2017 - Morning Break: CVS Buying Aetna; Uterus Transplant Baby; Your Brain on Drugs, Redux
December 15, 2017 - Social phobia linked to autism and schizophrenia
December 15, 2017 - Timestrip technology helping to prevent missed vaccinations
Harvard scientists discover hundreds of genetic switches that influence height

Harvard scientists discover hundreds of genetic switches that influence height

image_pdfDownload PDFimage_print

It’s been understood for decades that a host of factors – everything from pre- and post-natal health, nutrition, and genetics – play a role in determining height, but efforts to untangle the complex web of factors that contribute to height have long been stymied.

That picture, however, is becoming clearer, thanks to the work of Harvard scientists.

Led by Associate Professor of Human Evolutionary Biology Terence D. Capellini, a team of researchers discovered hundreds of genetic “switches” that have an influence on height and performed functional tests that demonstrated precisely how one such switch alters the function of a key gene involved in height differences. The study is described in a December 5 paper published in eLife.

“Large genome-wide association studies on upwards of 250,000 people found about 700 genetic regions associated with height,” Capellini said. “But within each region there could be many single DNA variants linked together, so there are potentially tens of thousands of variants spanning those regions. The question is how do you whittle that number down to those specific variants that influence height?”

The first step, Capellini said, was to filter the list of more than 60,000 genetic variants to those that are likely functional in the cartilage growth plates of bones. To do this they identified in the femurs of developing mice regions of the DNA that act as regulatory “switches” – that is, sequences of DNA that cause nearby genes to turn on or off. As part of that search, Capellini and colleagues focused on areas where the genome was “open,” or available for transcription using a technique called ATAC-seq.

The problem, however, is that process identifies every switch in the growth plate cartilage cell, many of which may not be involved in bone growth but rather basic cellular processes. To separate those “general” switches from those related to bone growth and thus likely height, the team performed the same test again, but on a different cell type, and identified sequences that were open in both. “If we find a common sequence that’s open in a brain cell and in a cartilage cell, we can say it likely turns on some gene that may be important for cells to live,” Capellini said. “So we filtered those out, but we didn’t ignore them completely, because they may actually be important. While we first concentrated on the bone-specific switches, we know there are a lot of inputs to height – it’s about the length of our bones, but we also know hormones trigger height, malnutrition can impact height, among other inputs so there may be general genetic factors that influence height.”

As part of that work, Capellini said, researchers also performed a number of “quality control” tests to ensure the unique switches they identified were actually involved in bone and cartilage development as well as height.

After performing those tests and filters, Michael Guo, an author on the study, was next able to determine how many of the 60,000 variants associated with height actually reside in on/off switches for bone. This resulted in a list of about 900 genetic variants.

To make sure that this process generated unique height signals, Capellini and colleagues performed additional analyses. “We took genome-wide analyses from other studies that had nothing to do with height and looked to see if we saw the same signal, and we didn’t, which makes sense,” he said. “We also looked at switches from other cell types to see if these genetic variants appeared, and they didn’t. That really suggests to us that the signals we’re seeing are very strong, it’s not just a property of the genome or a property of identifying these switches.”

The team then chose one on/off switch, associated with a gene known as Chondroitin Sulfate Synthase 1, or CHSY1, which plays a key role in how cartilage cells create the extra-cellular matrix that hardens into bone. In turn, the gene influences femur length in mice and humans.

“We did some tests to find out how this switch effects CHSY1 activity, and found that both versions – for taller height and shorter height – act as repressors on the gene,” Capellini said. “But surprisingly the height-increasing variant isn’t as strong.”

To verify that the switch indeed acts in a repressive manner, using CRISPR tools, researchers removed the switch or the variant altogether from human cartilage cells, and saw a very strong increase in the expression of the gene.

Going forward, Capellini and colleagues hope to use high-throughput functional methods to understand the role each variant plays in human height, and to develop other methods to test all 60,000-plus variants in order to study height in a more unbiased manner.

In addition to providing a new understanding of a complex human trait, the study may ultimately demonstrate how genetic tools might be used to understand other conditions – like macular degeneration, diabetes or even heart disease – that are tied to both environmental and genetic factors.

“For any disease or trait, being able to say here is a switch that turns a gene on or off, and here is the mutation in that switch that can effect it dramatically…that’s pretty powerful,” Capellini said. “That will allow us figure out what are the biological pathways that are worth targeting. The future of personalized medicine will rely on knowing what specific pieces of DNA are doing in the body, and this is one way to do that.”

Tagged with:

About author

Related Articles