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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
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Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 3. |
- Kuderna, Lukas F. K., et al.
(författare)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 4. |
- Wang, Dongdong, et al.
(författare)
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Split N and P addition decreases straw mineralization and the priming effect of a paddy soil : a 100-day incubation experiment
- 2019
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Ingår i: Biology and Fertility of Soils. - : Springer Science and Business Media LLC. - 0178-2762 .- 1432-0789. ; 55:7, s. 701-712
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Tidskriftsartikel (refereegranskat)abstract
- The effect of mineral fertilization and its application pattern on microbial activity and the subsequent CO2 and CH4 emissions arising from soil organic matter (SOM) or added substrate remains unclear. We quantified the decomposition of 13C-labeled straw and the priming effect (PE) governed by the N and P fertilizer application pattern during a 100-day experiment in a flooded soil. Straw addition increased the total CO2 and CH4 emissions. Straw mineralization increased by 30% and decreased by 19% after full and split NP application, respectively, compared with only straw addition. However, application of NP fertilization (full or split) inhibited straw-derived CH4 emissions compared with only straw addition. SOM decomposition was increased by straw addition, yielding a positive PE for CO2 emission. The application of split NP fertilization along with straw addition improved microbial activity, yielding the highest positive PE for CO2 emission. In contrast, compared with the control (no addition), split NP application decreased the positive PE for CH4 emission. Therefore, the straw-C-derived total CO2 equivalent emission was decreased by split NP application. These results were mainly attributable to the increased Olsen P, microbial biomass, enzyme activity, and straw-derived C microbial use efficiency of split NP application, which negatively affected the PE for CH4 emission; this was supported by the results of standardized total effects determined from structural equation models. Overall, compared with full application, split NP fertilizer application significantly decreased the straw-C mineralization rate and PE for CH4 emission, thereby mitigating greenhouse gas emission and SOM storage in paddy soil.
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