Mexican Biobank advances population and medical genomics of diverse ancestries

Nature, Journal Year: 2023, Volume and Issue: 622(7984), P. 775 - 783

Published: Oct. 11, 2023

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories complex trait architectures remain hidden owing insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural urban localities across all 32 states Mexico at a resolution of 1.8 million genome-wide markers with linked disease information creating valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution inference identity-by-descent segments, we inferred ancestral population sizes Mesoamerican regions over time, unravelling Indigenous, colonial postcolonial demographic dynamics2-6. We observed variation runs homozygosity among genomic different ancestries reflecting distinct and, turn, distributions rare deleterious variants. conducted association studies (GWAS) for 22 traits found that several are better predicted GWAS compared UK GWAS7,8. identified environmental factors associating variation, such as length genome predictor body mass index, triglycerides, glucose height. This study provides insights into dissects their architectures, both crucial making precision preventive medicine initiatives accessible worldwide.

Language: Английский

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Inference and applications of ancestral recombination graphs

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Language: Английский

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The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants

Science, Journal Year: 2024, Volume and Issue: 383(6686)

Published: Feb. 29, 2024

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ counts at birth persisted over time, normal memory and high γδ counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue development. Only a minority of these individuals were sick, infection, lymphoproliferation, and/or autoimmunity. also report 1 in 4000 from the Middle East South Asia are homozygous for common hypomorphic variant. They had but Although residual pre-TCRα expression drove more cells, autoimmune conditions frequent patients compared general population.

Language: Английский

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Earliest directly dated rock art from Patagonia reveals socioecological resilience to mid-Holocene climate

Science Advances, Journal Year: 2024, Volume and Issue: 10(7)

Published: Feb. 14, 2024

The timing for the evolution of capacity to inscribe landscape with rock art has global relevance. While this was an in-built when Homo sapiens first colonized Americas, heterogeneous distribution shows that it a facultative behavior arising under unknown socioecological conditions. Patagonia last region be explored by humans. its is globally important, remains largely undated absolute methods. We report earliest set directly radiocarbon-dated motifs from archaeological site Cueva Huenul 1 (northwestern Patagonia, Argentina), starting at 8.2 thousand years before present (ka B.P.), predating previous records several millennia, and encompassing over 3 ka (~130 human generations). This mid-Holocene “rock emergence” phase overlaps extremely arid conditions demographic stasis. suggest diachronic emerged as part resilient response ecological stress highly mobile low-density populations.

Language: Английский

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Estimating evolutionary and demographic parameters via ARG-derived IBD

PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(1), P. e1011537 - e1011537

Published: Jan. 8, 2025

Inference of evolutionary and demographic parameters from a sample genome sequences often proceeds by first inferring identical-by-descent (IBD) segments. By exploiting efficient data encoding based on the ancestral recombination graph (ARG), we obtain three major advantages over current approaches: (i) no need to impose length threshold IBD segments, (ii) can be defined without hard-to-verify requirement recombination, (iii) computation time reduced with little loss statistical efficiency using only segments set sequence pairs that scales linearly size. We demonstrate powerful inferences when true information is available simulated data. For inferred real data, propose an approximate Bayesian inference algorithm use it show even poorly-inferred short improve estimation. Our mutation-rate estimator achieves precision similar previously-published method despite 4 000-fold reduction in used for inference, identify significant differences between human populations. Computational cost limits model complexity our approach, but are able incorporate unknown nuisance misspecification, still finding improved parameter inference.

Language: Английский

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Limited role of generation time changes in driving the evolution of the mutation spectrum in humans

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 13, 2023

Recent studies have suggested that the human germline mutation rate and spectrum evolve rapidly. Variation in generation time has been linked to these changes, though its contribution remains unclear. We develop a framework characterize temporal changes polymorphisms within between populations, while controlling for effects of natural selection biased gene conversion. Application 1000 Genomes Project dataset reveals multiple independent arose after split continental groups, including previously reported, transient elevation TCC>TTC mutations Europeans novel signals divergence C>Gand T>A rates among population samples. also find significant difference groups sampled outside Africa old T>C predate out-of-Africa migration. This surprising signal is driven by TpG>CpG stems part from mis-polarized CpG transitions, which are more likely undergo recurrent mutations. Finally, relating parental age on de novo mutations, we show plausible cannot explain patterns observed different types jointly. Thus, other factors – genetic modifiers or environmental exposures must had non-negligible impact landscape.

Language: Английский

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Genealogies and oral histories as chronological networks: interfacing whakapapa (Māori genealogies) with Gregorian calendar year archaeological radiocarbon dates

Archaeometry, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Abstract Human genealogies serve multiple functions beyond documenting one's pedigree. They operate as complex social frameworks that structure knowledge, delimit group membership, explain historical causation, are political tools, and provide chronological foundations for understanding past events processes across diverse knowledge systems. Archaeologists, ethnologists, historians have long related information from associated histories to solar calendar years. However, unsystematic methodologies, contrasting ontologies, ethical issues limited these approaches. In this paper, we review previous attempts at relating human with We the network approach a new alternative, including maximum minimum Gregorian year limits each event's date estimate. consider method capable of greater transparency, adjustment information, hypothesis testing, internally consistent models. The efficacy is demonstrated case study Māori ( whakapapa ), oral kōrero tuku iho radiocarbon dates. Example genealogical estimates interfaced dates initial settlement Aotearoa New Zealand advent fortifications pā ) in Waikato region. conclude by discussing implications significance concerning Indigenous research priorities, data sovereignty principles.

Language: Английский

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Genetic and training adaptations in the Haenyeo divers of Jeju, Korea

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115577 - 115577

Published: May 1, 2025

Language: Английский

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Temporal challenges in detecting balancing selection from population genomic data

G3 Genes Genomes Genetics, Journal Year: 2024, Volume and Issue: 14(6)

Published: March 29, 2024

Abstract The role of balancing selection in maintaining genetic variation remains an open question population genetics. Recent years have seen numerous studies identifying candidate loci potentially experiencing selection, most predominantly human populations. There are however alternative evolutionary processes that may leave similar patterns variation, thereby confounding inference, and the expected signatures additionally change a temporal fashion. Here we use forward-in-time simulations to quantify statistical power detect using both site frequency spectrum- linkage disequilibrium-based methods under variety evolutionarily realistic null models. We find whilst spectrum-based little immediately after balanced mutation begins segregating, increases with time since introduction allele. Conversely, considerable allele is young, dissipates rapidly as increases. Taken together, this suggests effective at detecting long-term (>25N generations allele) over much shorter timescales (<1N generations), leaving large frame which current action selection. Finally, investigate extent mimic these patterns, demonstrate need for caution attempting distinguish from those neutral (e.g. structure admixture) well selective partial sweeps).

Language: Английский

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Evidence for dynastic succession among early Celtic elites in Central Europe

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(8), P. 1467 - 1480

Published: June 3, 2024

The early Iron Age (800 to 450 BCE) in France, Germany and Switzerland, known as the 'West-Hallstattkreis', stands out featuring earliest evidence for supra-regional organization north of Alps. Often referred 'early Celtic', suggesting tentative connections later cultural phenomena, its societal population structure remain enigmatic. Here we present genomic isotope data from 31 individuals this context southern Germany, dating between 616 200 BCE. We identify multiple biologically related groups spanning three elite burials far 100 km apart, supported by trans-regional individual mobility inferred data. These include a close biological relationship two richest burial mounds Hallstatt culture. Bayesian modelling points an avuncular individuals, which may suggest practice matrilineal dynastic succession Celtic elites. show that their ancestry is shared on broad geographic scale Iberia throughout Central-Eastern Europe, undergoing decline after late (450 BCE ~50 CE).

Language: Английский

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