Update on the Genetic Basis of Disorders of the Musculoskeletal System (ECTS 2013)

Medina-Gómez, Carolina; Rivadeneira, Fernando

doi:10.1038/bonekey.2014.3

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…Seven genes known to be associated with bone synthesis were identified by either iHS or G2D analysis. Among them, FLNB, EPHB1, and TSPAN5 have been functionally shown to affect body size through gene knockout or knockdown experiments in mice (Iwai et al 2007;Farrington-Rock et al 2008;Benson et al 2012;Zhou et al 2014); and FLNB, AXDND1, ZBTB38, and GAREM have been shown to be associated with human height in multiple populations (Lettre et al 2008;Weedon et al 2008;Kim et al 2012;Wang et al 2013;Medina-Gomez and Rivadeneira 2014;Wood et al 2014). EPHB1 was reported to be genetically associated with height in African Pygmies (Jarvis et al 2012).…”

Section: Candidates Of Adaptation In Western African Pygmy Groupsmentioning

confidence: 99%

Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

et al. 2016

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African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors.

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Section: Candidates Of Adaptation In Western African Pygmy Groupsmentioning

confidence: 99%

Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

et al. 2016

View full text Add to dashboard Cite

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Whole genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

Hsieh

Veeramah

Lachance

et al. 2015

Preprint

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(250 words in total)28 African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged 29 from other anatomically modern humans, and they likely experienced strong selective pressures due to 30 their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we 31 sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed 32 these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. 33To account for the complex demographic history of these populations that includes both isolation and 34 gene flow, we fit models using the joint allele frequency spectrum and validated them using independent 35 approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers 36 and Pygmies, 90,000 or 150,000 years ago. We also find that bi-directional asymmetric gene-flow is 37 statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as 38 previously suggested. We then applied complementary statistics to scan the genome for evidence of 39 selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were 40 biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this 41 bias, we assigned P-values for candidates using whole-genome simulations incorporating demography 42 and variation in both recombination and mutation rates. We found that genes and gene sets involved in

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Update on the Genetic Basis of Disorders of the Musculoskeletal System (ECTS 2013)

Cited by 2 publications

References 12 publications

Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

Whole genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

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