Dataset Information

Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans.

ABSTRACT: Tibetans are the ideal population to study genetic adaptation in extreme environments. Here, we performed systematic phenotyping of 11,880 highlanders, covering 133 quantitative traits of 13 organ systems. We provided a comprehensive phenotypic atlas by comparing altitude adaptation and altitude acclimatization. We found the differences between adaptation and acclimatization are quantitative rather than qualitative, with a whole-system "blunted effect" seen in the adapted Tibetans. We characterized twelve different functional changes between adaptation and acclimatization. More importantly, we established a landscape of adaptive phenotypes of indigenous Tibetans, including 45 newly identified Tibetan adaptation-nominated traits, involving specific changes of Tibetans in internal organ state, metabolism, eye morphology, and skin pigmentation. In addition, we observed a sex-biased pattern between altitude acclimatization and adaptation. The generated atlas of phenotypic landscape provides new insights into understanding of human adaptation to high-altitude environments, and it serves as a valuable blueprint for future medical and physiological studies.

SUBMITTER: He Y

PROVIDER: S-EPMC10481350 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans.

He Yaoxi Y Zheng Wangshan W Guo Yongbo Y Yue Tian T Cui Chaoying C Ouzhuluobu Zhang Hui H Liu Kai K Yang Zhaohui Z Wu Tianyi T Qu Jia J Jin Zi-Bing ZB Yang Jian J Lu Fan F Qi Xuebin X Su Bing B

iScience 20230818 9

Tibetans are the ideal population to study genetic adaptation in extreme environments. Here, we performed systematic phenotyping of 11,880 highlanders, covering 133 quantitative traits of 13 organ systems. We provided a comprehensive phenotypic atlas by comparing altitude adaptation and altitude acclimatization. We found the differences between adaptation and acclimatization are quantitative rather than qualitative, with a whole-system "blunted effect" seen in the adapted Tibetans. We characteri ...[more]

PMID: 37680474

Similar Datasets

Project description:BackgroundRepetitive action, resistance to environmental change and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. We then investigated the behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice. Both of these mutations are found in clinical conditions and have been associated with ASD.MethodsWe used advances in computer vision and deep learning, namely a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple timescales using a single popular behavioral assay, the open-field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait.ResultsBoth Cntnap2 knockouts and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants and Cntnap2 knockouts showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure to adapt took the form of maintained ambling, turning and locomotion, and an overall decrease in grooming. However, adaptation in these traits was similar between wild-type mice and Cntnap2 knockouts. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy.LimitationsGenetic risk factors for autism are numerous, and we tested only two. Our pipeline was only done under conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability.ConclusionsOur automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as quantitative diagnosis criteria.

Project description:Pham, Luu V., Christopher Meinzen, Rafael S. Arias, Noah G. Schwartz, Adi Rattner, Catherine H. Miele, Philip L. Smith, Hartmut Schneider, J. Jaime Miranda, Robert H. Gilman, Vsevolod Y. Polotsky, William Checkley, and Alan R. Schwartz. Cross-sectional comparison of sleep-disordered breathing in native Peruvian highlanders and lowlanders. High Alt Med Biol. 18:11-19, 2017.BackgroundAltitude can accentuate sleep disordered breathing (SDB), which has been linked to cardiovascular and metabolic diseases. SDB in highlanders has not been characterized in large controlled studies. The purpose of this study was to compare SDB prevalence and severity in highlanders and lowlanders.Methods170 age-, body-mass-index- (BMI), and sex-matched pairs (age 58.2 ± 12.4 years, BMI 27.2 ± 3.5 kg/m2, and 86 men and 84 women) of the CRONICAS Cohort Study were recruited at a sea-level (Lima) and a high-altitude (Puno, 3825 m) setting in Peru. Participants underwent simultaneous nocturnal polygraphy and actigraphy to characterize breathing patterns, movement arousals, and sleep/wake state. We compared SDB prevalence, type, and severity between highlanders and lowlanders as measured by apnea-hypopnea index (AHI) and pulse oximetry (SPO2) during sleep.ResultsSleep apnea prevalence was greater in highlanders than in lowlanders (77% vs. 54%, p < 0.001). Compared with lowlanders, highlanders had twofold elevations in AHI due to increases in central rather than obstructive apneas. In highlanders compared with lowlanders, SPO2 was lower during wakefulness and decreased further during sleep (p < 0.001). Hypoxemia during wakefulness predicted sleep apnea in highlanders, and it appears to mediate the effects of altitude on sleep apnea prevalence. Surprisingly, hypoxemia was also quite prevalent in lowlanders, and it was also associated with increased odds of sleep apnea.ConclusionsHigh altitude and hypoxemia at both high and low altitude were associated with increased SDB prevalence and severity. Our findings suggest that a large proportion of highlanders remain at risk for SDB sequelae.

Dataset Information

Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans.

Publications

Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets