ED Guidebook2020_21Digital


Stress really can cause gray hair It turns out that the old wives’ tale that stress can turn your hair gray may be true. Scientists have found that when dark-

DNA double helix can form four-stranded regions

Short, tall and genetic variation Peruvians are some of the shortest people in the world, with average heights of about five feet five inches for men and about five feet for women. A Harvard Medical School-led team of researchers believe they have found the genetic contributor to this short stature in Peruvians. In fact, they report they have identified the single largest genetic contributor to height known to date. The research team conducted a genome-wide association study using height and genotyping data from over 3,000 individu- als from nearly 2,000 households in Lima, Peru. They found five single nucleotide changes, also called single-nucleotide polymorphisms (SNPs), located on areas of the gene FBN1 that are associated with height. FBN1 encodes the protein fibrillin 1, which is involved in tissue development, homeostasis and repair. One of the variants of FBN1 was associated with an almost 2.2-centimeter (0.87") decrease in height that doubled to an almost 4.4-centimeter (1.7") decrease if the individual had two copies of the variant. Height variants discovered prior to this study only influence height by less than 0.5 centimeters, making this the largest variant of height ever reported. Contrary to the effects of the newfound FBN1 variants, previ- ously reported mutations in the FBN1 gene cause Marfan or Marfan-like syndromes, which are characterized by extremely tall stature. This highlights how genetic variants in the same gene can have vastly different effects. REFERENCE: Asgari, S. et al. A positively selected FBN1 missense variant reduces height in Peruvian individuals. Nature (2020) 582: 234-239 doi: 10.1038/ s41586-020-2302-0. southern Pacific Ocean were originally settled by Asian migrants but were colonized by Europeans during the 16th century. Research- ers have long been intrigued by the possibility that Native Americans and Polynesian islanders came in contact before European inter- action. As proof of such a meeting, supporters of the idea point to architectural similarities between Polynesian and Native American ceremonial sites, and agricultural clues such as the presence on the islands of the American sweet potato which exists nowhere else outside of pre-Columbian Americas. To date, however, genetic data has never supported this idea. In a recent study published in Nature , researchers analyzed the genomes of more than 800 people from 15 Native American populations along the Pacific coast of Central and South America and 17 groups currently living on the Polynesian islands. Through a combination of genetic analysis and historical records, the data suggests Native Americans and Polynesians encountered one anoth- er and produced children during a single time period around 1200 CE, nearly 500 years before Europeans arrived. This study highlights the usefulness of genomic analysis to allow researchers to track human migration and contact events that are invisible from an archaeological or historical standpoint. REFERENCE: Ioannidis, A.G. et al. Native American gene flow into Polynesia predating Easter Island settlement. Nature (2020) 583: 572-577 doi: 10.1038/s41586- 020-2487-2. Native American contributions to Polynesian peoples The Polynesian islands in the central and

When someone says “DNA” an image of a double helix shape probably comes to mind. DNA, or deoxyribonucleic acid, usually forms as the classic double helix shape composed of two strands of nucleic acids wound around each other. However, other structures of DNA, such as quadruple helix structures, have been created in test tubes in labs or found in cancer cells. DNA G-quadruplexes (G4s) form within traditional double strand- ed DNA helices when guanine-rich stretches of DNA fold into four-stranded structures through the bonding of guanine bases with each other. G4s are difficult to detect in living cells because the tech- niques required to visualize the DNA kill the cells. To solve this prob- lem, an international research team invented a fluorescent marker to attach to G4s in living cells without disrupting the DNA. Using their new marker, the research team was able to visualize G4s in healthy, living human cells. This study proves G4s exist in cells as stable structures created by normal processes, although their function is still widely unknown. Because G4s form and disappear quickly, the research group thinks they might function to temporarily hold open DNA to facilitate transcription. REFERENCE: Di Antonio, M. et al. Single-molecule visualization of DNA G-quadru- plex formation in live cells. Nature Chemistry . (2020) doi: 10.1038/s41447-020-0506-4.

furred mice are exposed to experimental stress they turn white in mere days. After ruling out both the immune system and stress hormone involvement, the scientists discovered that the mice’s sympathetic nervous systems were to blame for the whitened hair. The sympathetic nervous system is respon- sible for an animal’s fight-or-flight response in the face of stress or fear. The stress trig- gered fight-or-flight response causes the release

of a neurotransmitter called norepinephrine. Norepinephrine causes hair follicle stem cells to prematurely differentiate into melanocytes, the cells that give hair its color. Normally, a population of stem cells exists to replenish melanocytes as they die. However, in the stressed mice the stem cell pool was rapidly depleted, leaving the mice with no new melanocytes to continue producing hair color. By analyzing gene expression in stressed stem cells, the scientists discovered changes in several cell cycle regulatory genes. Activation of such genes triggers the stem cells to leave the G0 resting phase of the cell cycle, enter the cell cycle and terminally differentiate into melanocytes, thereby depleting the stem cell pool. The researchers tested the mechanism on human hair follicle stem cells and found similar results. This study suggests that stress, in addition to aging, could contribute to the graying of hair in humans. REFERENCE: Zhang, B. et al. Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature (2020) 577:676-681 doi: 10.1038/s41586-020- 1935-3. Finding free-floating mitochondria Mitochondria are called the powerhouse of the cell because they produce most of the chemical energy needed for cells to function properly. Through cellular respiration, these double- membrane-bound organelles convert oxygen and molecules from food into usable energy called adenosine triphosphate (ATP). While most mitochondria exist within cells, a study published in The FASEB Journal suggests that intact, functional mitochondria can circulate in blood without a cell carrier. The researchers were studying cell-free mitochondrial DNA fragments as a potential cancer biomarker when they noticed that certain fragments were longer and more resistant to degradation than others. Upon further investigation, they identified two popula- tions of cell-free mitochondrial DNA: small, degraded fragments, and long, full-length copies of the mitochondrial genome. Through the use of a wide range of techniques, the scientists concluded that the free-floating, full-length mitochondria were functional, respiratory organelles like their cell bound counterparts. The function of the free-floating mitochondria is currently unknown. The researchers who made the discovery propose that the indepen- dent mitochondria may be released by cells for signaling purposes, although more work is needed to validate this hypothesis. Whatever their function, it is an intriguing finding that mitochondria can func- tion normally while drifting around in the blood of healthy people. REFERENCE: Dache, Z. et al. Blood contains circulating cell-free respiratory compe- tent mitochondria. The FASEB Journal (2020) 34:3616-3630 doi: 10.1096/fj.201901917RR.

Getting by on 20 winks of sleep For most people, a good night’s beauty sleep involves an average of 8 hours of sleep per night. Waking up after a poor night’s sleep can leave you feeling foggy and unwell. In fact, sleeping for less than 6 hours a night several days in a row leads to a decline in cognitive abilities for some people. Chronic sleep deprivation contributes to several disorders including obesity, heart disease, high blood pressure, diabetes and depression. However, we all know someone who functions perfectly fine on less sleep, but how? It turns out that their genes may be the answer. By studying families that require less than the average amount of sleep to feel fully rested, a group of researchers identified several genetic mutations they think dictate the amount of sleep a person requires. Two genes in which they identified mutations, ADRB1 and NPSR1 , both encode proteins that are involved in sleep behavior. After identifying the potential candidate mutations, research- ers bred rats and mice with the same mutations and studied their sleep habits. Rats with the ADRB1 mutation slept about 55 minutes less per day and had altered activity in the dorsal pons area of the brain, known to regulate sleep. Mice with NPSR1 mutations also slept less without the obvious effects on health or memory associated with chronic sleep deprivation. In addition to feeling fully rested with almost half the amount of sleep required by the average person, the families with these genetic variants do not appear to suffer negative health consequences, although longer-term studies are necessary to confirm this. It might be possible to develop drugs to mimic the effects of these mutations, but the researchers caution that they might produce harmful side effects since these genes are also involved in stress and fear regulation. REFERENCES: Shi, G. et al. A rare mutation of ß 1 -Adrenergic receptor affects sleep/wake behaviors. Neuron . (2019) 103:1044-1055 doi: 10.1016/j. neuron.2019.07.026. Xing, L. et al. Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation. Science Translational Medicine . (2019) 11:eeas2014 doi: 10.1126/scitranslmed.aax2014.

Genetic signatures of the slave trade

An estimated 12.5 million people were forcibly removed from African countries and transported across the Atlantic Ocean to the Americas during the transatlantic slave trade. Their arrival changed the Amer- icas not only culturally, psychologically, and sociologically over time, but also genetically. For many modern-day African Americans, their ancestral roots are defined by this transatlantic migration. The genetics company 23andMe ® set out to help understand the genetic contributions of these mass movements of people by performing the largest DNA study of African ancestry in the Americas. Over the past decade, researchers studied genetic samples from over 500,000 participants living along the West Coast of Africa and along the eastern coastlines of North, Central, and South Americas where slaves are known to have been traded. With the help of historians, researchers compared the genetic profiles with historical shipping documents from slave voyages. They concluded that the proportion of individuals forced from Africa to the Americas is mirrored in genetic similarities between individuals from those regions. For example, the results confirmed that most Americans of African descent have genetic origins in Angola and the Democratic Republic of Congo, which is consistent with historical records. Variation from the expected genetic patterns can be explained by an increase in secondary slave trading within the Americas after the transatlantic slave trade ended, variable survival rate of slaves in different parts of the Americas and regional differences in the treat- ment of slaves. This study shows how genetic signatures can be used to effectively help trace the movements of populations of people that occurred hundreds of years ago. REFERENCE: Micheletti, S.J. et al. Genetic consequences of the Transatlantic slave trade. The American Journal of Human Genetics (2020) 107: 265-277 doi: 10.1016/j. ajhg.2020.06.012.




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