Dieci geni spiegano perché i tibetani riescono a sopravvivere a 4-5.000m senza disturbi.

Il segreto genetico per vivere in Tibet senza problemi – Scoperti dieci geni, esclusivi dei tibetani, che permettono di adattarsi alle alte quote Riescono a vivere sul tetto del mondo senza manifestare alcun sintomo del ‘mal di montagna’ che, ad alta quota, non risparmia neppure gli scalatori più allenati. Nel Dna dei tibetani si nasconde un pugno di geni, per la precisione 10, che permettono a questo popolo di resistere agli effetti dell’aria rarefatta. Geni esclusivi che hanno a che fare con la gestione dell’ossigeno da parte dell’organismo, e che risultano assenti nel genoma di altre popolazioni (per esempio gli abitanti delle Ande) pur avvezze all’atmosfera montana. A svelare il segreto dei tibetani sono gli scienziati americani dell’università dello Utah, autori di uno studio pubblicato su ‘Science’. Il team Usa ha analizzato il Dna estratto da campioni di sangue prelevato in 75 villaggi tibetani a 4.500 metri d’altezza. In collaborazione con un gruppo di colleghi dell’università cinese di Qinghai, i ricercatori hanno quindi confrontato il genoma dei tibetani con quello di popolazioni residenti a bassa quota in Cina e Giappone. Hanno così scoperto che i tibetani possono contare su un ‘tesoretto’ di 10 geni peculiari, due dei quali controllano i livelli ematici di emoglobina (la ‘vettura’ proteica che trasporta l’ossigeno nel sangue), evitando l’eccesso di globuli rossi tipico di altre popolazioni residenti ad alta quota.“Per la prima volta abbiamo individuato i geni che spiegano questo meccanismo di adattamento”, sottolinea Lynn Jorde dell’University of Utah School of Medicine di Salt Lake City. Questo studio, aggiunge Josef Prchal dello stesso ateneo, potrà contribuire allo sviluppo di terapie contro i disturbi più o meno gravi legati all’altitudine. La differenza fra le genti del Tibet, che vivono e lavorano a circa 4.800 metri di altezza, e tutti gli altri popoli, compresi gli andini e gli etiopi che abitano altipiani e montagne a migliaia di metri sopra il livello del mare, sta in una decina di geni. Dieci geni che spiegano perché i tibetani riescono a sopravvivere a quelle altitudini senza i disturbi (tipo mal di testa, difficoltà di respiro, tachicardia o, ancora peggio, edema cerebrale fino a situazioni che possono mettere in pericolo la vita) che, invece, colpiscono i viaggiatori non allenati (ma anche scalatori professionisti). Non solo: spiegano anche perché i tibetani non soffrono di policitemia, cioè di un eccesso di globuli rossi nel sangue (prodotti in risposta alla mancanza di ossigeno) che si evidenzia, invece, in altre popolazioni che vivono ad alte quote. …

Vorreste vivere in Tibet?: Senza 10 geni speciali l’altitudine vi ucciderebbe

La differenza fra le genti del Tibet, che vivono e lavorano a circa 4.800 metri di altezza, e tutti gli altri popoli, compresi gli andini e gli etiopi che abitano altipiani e montagne a migliaia di metri sopra il livello del mare, sta in una decina di geni. Dieci geni che spiegano perché i tibetani riescono a sopravvivere a quelle altitudini senza i disturbi (tipo mal di testa, difficoltà di respiro, tachicardia o, ancora peggio, edema cerebrale fino a situazioni che possono mettere in pericolo la vita) che, invece, colpiscono i viaggiatori non allenati (ma anche scalatori professionisti). Non solo: spiegano anche perché i tibetani non soffrono di policitemia, cioè di un eccesso di globuli rossi nel sangue (prodotti in risposta alla mancanza di ossigeno) che si evidenzia, invece, in altre popolazioni che vivono ad alte quote.

Nel corso dei secoli, gli abitanti del «Tetto del mondo» hanno selezionato una serie di geni, dieci appunto, che solo loro possiedono e che hanno a che fare con il trasporto o l’utilizzo dell’ossigeno da parte dell’organismo. Questi geni sono stati scoperti da un’équipe di ricercatori americani dell’University of Utah School of Medicine a Salt Lake City e cinesi della Qinghai University Medical School che hanno pubblicato la loro ricerca su Science.

«È la prima volta – ha commentato Lynn B. Jorde dell’University of Utah – che abbiamo identificato geni che possono spiegare l’adattamento alle elevate altitudini». Lo studio ha preso il via da un’idea di Josef T. Prchal , ematologo e internista all’University of Utah, esperto in pollicitemie, che ha preso contatto con Jorde: così una ricercatrice del laboratorio di quest’ultimo, Tatum S. Simonson ha organizzato una spedizione in Tibet per raccogliere campioni di Dna nella popolazione, in collaborazione con Ge Re-li, direttore del Research Center for High Altitude Medicine alla University of Qinhai a Xining. In totale sono stati prelevati campioni di sangue da 75 persone e, dopo l’eliminazione di quelli che appartenevano a persone con rapporti di parentela, ne sono stati analizzati 31 (sufficienti per ottenere risultati statisticamente significativi) per un totale di un milione di mutazioni genetiche.

Dopo un accurato confronto fra le varianti del Dna dei campioni prelevati dai tibetani con quelle di altre persone che vivevano ad altitudini più basse rispetto al livello del mare, sono stati appunto identificati dieci geni che hanno a che fare con il metabolismo energetico, l’emoglobina e il monossido di azoto che ha un ruolo nell’ossigenazione dei tessuti e nella prevenzione della policitemia. La comprensione di questi meccanismi non ha soltanto un valore conoscitivo: secondo gli esperti, potrebbe aiutare a mettere a punto nuove terapie per comuni malattie come l’ipertensione polmonare o l’edema polmonare e cerebrale che colpiscono persone in tutto il mondo. http://www.blitzquotidiano.it/scienze/tibet-altitudine-10-geni-university-of-yutah-quinhay-university-medical-school-375341/

The Genetics of High-Altitude Living, by Ann Gibbons on May 13, 2010 2:38 PM

Call it Sherpa envy. Mountain climbers have long wished they could discover—and bottle in a drug—how Tibetans live and work high in the Himalayas without getting altitude sickness. Now researchers have discovered two new gene variants that help Tibetans use oxygen more efficiently than people who live at low altitudes; natural selection favored these variants in Tibetans, whose ancestors have lived at high altitude for thousands of years.

Researchers have been mystified as to how Tibetans have thrived at altitudes over 4400 meters (14,435 feet). Some high-altitude people, such as Andean highlanders, have an adaptation that adds more oxygen-rich hemoglobin to their blood. But many highland Tibetans, researchers have found, have less hemoglobin in their blood. That helps them avoid serious problems caused by too much hemoglobin, but Tibetans with this so-called decreased hemoglobin phenotype must somehow use small amounts of oxygen efficiently to get enough of it to their limbs while exercising at high altitude. Researchers have been unable to pinpoint the genes that are responsible for this remarkable balancing act in their blood.

In a report published online today in Science, a team of Chinese and American researchers identified variants of two genes involved in oxygen processing that are found in most Tibetan highlanders. The researchers used two methods to search for these genes. First, they scanned DNA registries for genes that might be involved in regulating oxygen in the blood and identified 247 candidate genes that vary in different populations. Then they analyzed segments of DNA that include those 247 genes in 31 unrelated Tibetans, 45 Chinese, and 45 Japanese lowland people whose DNA was genotyped in the HapMap Project. By identifying regions that had a characteristic signature of being strongly altered by natural selection, they were able to identify relatively new gene variants that had swept through highland Tibetans, but not Chinese or Japanese lowlanders. They finally homed in on 10 genes, including two, EGLN1 and PPARA, that were found at the highest frequency in Tibetans who had the least oxygen in their blood.

The researchers found that people who have more copies of the gene variants (by inheriting a copy of each advantageous variant from both parents), had the least amount of oxygen in their blood and used it more efficiently than people without either variant, or only one copy from one parent. “Tibetans with these genes appear to be much more efficient with the oxygen they have,” says senior author Lynn Jorde, a human geneticist at the University of Utah School of Medicine in Salt Lake City.

The next step is to do functional studies to see how these gene variants actually regulate oxygen levels.

“This is a groundbreaking paper,” says geneticist Anna Di Rienzo of the University of Chicago in Illinois. “These genes seem to have relatively large phenotypic effects.”

But although these genes apparently lower the level of oxygen in the blood, they are responsible for only part of the story of the Tibetans’ adaptation and would not by themselves make a beneficial drug for climbers. “Just lowering your hemoglobin alone would make you less well adapted to high altitude,” points out Jorde. Researchers are still searching for the genes that orchestrate how Tibetans transport low levels of oxygen so efficiently to their tissues—a process that may involve using nitric oxide to boost their blood volume.

http://news.sciencemag.org/sciencenow/2010/05/the-genetics-of-high-altitude-li.html

Genetic Evidence for High-Altitude Adaptation in Tibet – Published Online May 13, 2010; Science DOI: 10.1126/science.1189406

Tatum S. Simonson,¹ Yingzhong Yang,² Chad D. Huff,¹ Haixia Yun,² Ga Qin,² David J. Witherspoon,¹ Zhenzhong Bai,² Felipe R. Lorenzo,³ Jinchuan Xing,¹ Lynn B. Jorde,^1,* Josef T. Prchal,^1,3,* RiLi Ge^2,*

Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia response pathways in humans.

¹ Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
² Research Center for High Altitude Medicine, Qinghai University Medical School, Xining, Qinghai 810001, People’s Republic of China.
³ Division of Hematology and Department Pathology (ARUP), University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

To whom correspondence should be addressed. E-mail: lbj@genetics.utah.edu (L.B.J); josef.prchal@hsc.utah.edu (J.T.P.); geriligao@hotmail.com (R.G.)

Received for publication 10 March 2010. Accepted for publication 6 May 2010.

http://www.sciencemag.org/cgi/content/abstract/science.1189406

Tibetans Get Their Blood Flowing, by Michael Balter on October 29, 2007

Tibet is the highest region in the world, with an average altitude of 4000 meters. Yet Tibetans seem to do fine despite the low oxygen levels at these dizzying heights. Now researchers have figured out how: Tibetans compensate for the lack of oxygen by boosting the supply of blood to their tissues. The findings may aid efforts to develop treatments for oxygen deprivation after heart attacks and organ transplants.

A lowlander exposed to the low oxygen concentrations of high elevations can quickly fall victim to altitude sickness, whose symptoms include nausea, dizziness, and fatigue. But Tibetans do not suffer from altitude sickness. Previous studies have shown that they have lower oxygen concentrations in the blood of their arteries (ScienceNOW, 16 September 2004). Yet the body tissues of Tibetans consume just as much oxygen as those of people who live at sea level. A group of researchers led by physical anthropologist Cynthia Beall of Case Western Reserve University in Cleveland, Ohio, hypothesized that Tibetans might offset low oxygen levels by increasing blood flow.

Beall and her co-workers studied 88 healthy volunteers from the Tibetan district of Panam Xiang, where the elevation is 4200 meters. They compared the Tibetans to a group of 50 volunteers from the Cleveland area, which is about 200 meters above sea level. The team measured the subjects’ blood flow noninvasively using a rubber gauge fitted around their forearms. Twice as much blood coursed through the arms of the Tibetans as through the arms of the lowlanders, even though heart rates and blood pressures were no different between the two groups, the researchers report online this week in the Proceedings of the National Academy of Sciences.

To figure out what accounts for this dramatic increase, the researchers gauged nitric oxide levels in each group. Nitric oxide and its metabolites cause blood vessels to expand and thus carry more blood. The team found that the blood of Tibetans had more than 10 times the concentration of biologically active nitric oxide breakdown products, such as nitrate and nitrite, than did blood from people who lived at sea level, signifying a high level of nitric oxide in their bloodstreams. That’s “unprecedented for healthy people,” the authors say, although the Tibetans do not seem to suffer any ill effects.

“These remarkable data in Tibetans provide a beautiful demonstration of how nature has evidently exploited” nitric oxide levels to offset the effects of high altitude, says Jonathan Stamler, a cardiovascular disease researcher at Duke University Medical Center in Durham, North Carolina. Mark Gladwin, a researcher in pulmonary medicine at the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Maryland, says that the nitrite levels in the Tibetans’ blood are similar to those NHLBI researchers are using to treat heart and liver injuries caused when blood is restored to oxygen-deprived tissues in experimental animals. This correspondence provides additional evidence that these concentrations might have therapeutic value, he says. Gladwin adds that NHLBI is now planning a clinical trial that would use similar levels of nitrite to treat heart-attack victims. http://news.sciencemag.org/sciencenow/2007/10/29-02.html

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