Human molecular genetics最新文献

{"title":"Disease-specific biomarkers of pathogenic HRAS variants in human immortalized keratinocytes.","authors":"Thomas Mair, Theresa Nauth, Hannah Voß, Verena Rickassel, Sophia Deden, Hartmut Schlüter, Georg Rosenberger","doi":"10.1093/hmg/ddag050","DOIUrl":"10.1093/hmg/ddag050","url":null,"abstract":"<p><p>Pathogenic germline variants in HRAS result in the non-mosaic RASopathy Costello syndrome (CS), a rare developmental disorder affecting various tissues including the skin and with > 80% of patients showing the HRAS p.G12S variant. Postzygotic HRAS variants have been identified in disorders of the skin, so-called mosaic RASopathies (e.g. Nevus sebaceous syndrome) and > 85% of patients show the HRAS p.G13R variant. Oncogenic HRAS variants are common in dermatological and other malignancies, with HRAS p.G12V being one of the most common variants. The three disease entities are characterized by different skin manifestations reflecting HRAS function as modulator of epidermal homeostasis and suggesting HRAS variant-specific functional consequences. We analyzed permanent human keratinocytes (HaCaT cells) stably expressing disease-specific HRAS variants (p.G12S, p.G12V, p.G13R) to identify unique biological consequences underlying the phenotypical pleiotropy of HRAS-associated disorders. Immunoblotting experiments revealed significant functional differences between HRAS variants in the expression and/or activation of cell fate markers, signaling proteins, and cell contact molecules. These differences are reflected in different cell biological consequences regarding proliferation, adhesion, and migration. By applying mass spectrometry and collecting data on protein interactions (interactome), protein phosphorylation (phosphoproteome), and protein expression (proteomics), we verified HRAS variant-specific functional consequences and revealed novel and pleiotropic pathophysiological features for each of the three HRAS variants. HRAS p.G13R induced strongest molecular changes suggesting most serious pathobiological consequences, and HRAS p.G12S and p.G12V predominantly interfered with cellular signaling. Taken together, our data underscore the existence of HRAS variant-specific qualities of dysregulation and describe a differential pathophysiological architecture of HRAS-associated phenotypes.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FXN protomutations are the source of pathogenic expanded GAA alleles in Friedreich ataxia and explain its unequal population distribution.","authors":"Morgan C Devore, Christina Lam, Emily Xiao, Jeremy Devore, Kassandra R C McCain, Graham Wiley, Courtney C Park, David R Lynch, Sanjay I Bidichandani","doi":"10.1093/hmg/ddag046","DOIUrl":"10.1093/hmg/ddag046","url":null,"abstract":"<p><p>Friedreich ataxia (FRDA) is a recessive condition that is typically caused by inheriting an expanded GAA repeat (usually > 500 triplets) in the FXN gene from both parents who are heterozygous carriers of the expanded (E) allele. E alleles, which are evolutionarily derived from non-pathogenic long normal (LN) alleles (≥12 triplets), occasionally arise de novo via intergenerational expansion of premutation alleles (34-60 triplets). However, why FRDA susceptibility is limited to Eurasians, and how the prevalence of E alleles is sustained in susceptible populations are incompletely understood. Sequencing of the FXN locus revealed two major subclasses of E alleles, which have originated from a subset of Eurasian LN alleles, termed protomutations. Haplotype identity, the observed size continuum of protomutation-premutation-E alleles, and evidence of intergenerational instability in a protomutation allele, together support a dynamic relationship wherein protomutations can transition to premutation and E alleles. Consistent with the exclusive prevalence of FRDA in Eurasia, protomutations are absent in sub-Saharan Africa, where E alleles did not develop despite a relatively high prevalence of LN alleles. However, genetic admixture has introduced a slight risk of FRDA in African Americans. Analysis of ancient DNAs revealed that protomutations have existed in Europe and Western Asia for thousands of years, with evidence of spread to Europe via early Neolithic farmers. These data indicate that FXN protomutations serve as a reservoir for the generation of premutation and E alleles, and for millennia have sustained the geographically-defined population distribution of FRDA.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRMT1 drives cervical cancer progression by orchestrating cell growth, migration, and angiogenesis.","authors":"Wen-Ye Liu, Han-Wen Huang, Jin-Ni Ma, Lu Xue","doi":"10.1093/hmg/ddag044","DOIUrl":"10.1093/hmg/ddag044","url":null,"abstract":"<p><p>PRMT1 is an important regulator implicated in multiple malignancies, yet its role in cervical cancer remains unclear. In this study, we investigated the functional significance of PRMT1 in cervical cancer using integrated public transcriptomic datasets, CRISPR/Cas9-edited HeLa cells, and an in vivo xenograft model. PRMT1 was upregulated in cervical cancer tissues and was associated with histological grade, clinical stage, and lymph node metastasis status, although it was not significantly associated with overall survival. In vitro, PRMT1 depletion inhibited cell proliferation, colony formation, aggregation, and migration, and was accompanied by mitochondrial apoptosis, S-phase arrest, altered c-Myc and PI3K/AKT signaling, and changes in EMT-related marker expression. Conditioned medium from PRMT1-knockout cells also impaired human umbilical vein endothelial cells (HUVECs) tube formation and was associated with reduced MMP-9 expression. In vivo, PRMT1 knockout significantly suppressed xenograft growth and reduced Ki-67 and CD31 expression. Collectively, these findings suggest that PRMT1 is an important regulator associated with cervical cancer progression and a potential candidate biomarker for prognostic assessment and therapeutic targeting, although its clinical prognostic value requires further validation.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIRAGE: a multimodal deep learning framework for interpretable risk assessment of high myopia from genetic and retinal imaging data.","authors":"Yijun Zhou, Shuaishuai Gao, Tao Wang, Wei Dai, Kaicheng Ye, Bowei Ma, Yao Zhou, Shuyan Fan, Yuanyuan Gui, Wenhao Ma, Zhen Ji Chen, Shilai Xing, Jianzhong Su, Jia Qu, Jian Yuan, Yinghao Yao","doi":"10.1093/hmg/ddag040","DOIUrl":"10.1093/hmg/ddag040","url":null,"abstract":"<p><p>High myopia (HM) is a complex condition influenced by both genetic and environmental factors, yet its early prediction and clinical intervention remain challenging due to heterogeneous progression patterns. To support early identification of individuals at risk for HM, we developed MIRAGE, a deep learning framework combining exome-wide genotypes with fundus images for personalized prediction. The model combines DeepExGRS for genetic risk modeling and a convolutional network for imaging, fused via a gating attention mechanism. Applied to a cohort of 1991 individuals, MIRAGE achieved high predictive accuracy (AUC = 0.963), outperforming unimodal models. Interpretation using Integrated Gradients and Shapley values identified key genes (e.g. GJD2, FGF1) and image regions (optic disc, macula) contributing to predictions. Further, deep learning-based genetic risk models (DeepcvGRS and DeeprvGRS) outperformed traditional polygenic risk scores, capturing nonlinear interactions and improving HM prediction. Interaction analysis using Shapley interaction scores revealed 314 significant gene-gene interactions, including biologically relevant pairs such as PRSS56-GLI3 and SEMA4D-FRY. Overall, MIRAGE offers a scalable, interpretable, and accurate approach for HM risk stratification, paving the way to early intervention guided by both genetics and retinal imaging.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited penetrance of dominantly inherited AIRE variants in a population-based cohort.","authors":"Suraj N Ramchand, Jacques Murray Leech, Luke N Sharp, Georgia Bonfield, Amber M Luckett, Michael N Weedon, Kashyap A Patel, Gareth Hawkes, Matthew B Johnson","doi":"10.1093/hmg/ddag047","DOIUrl":"10.1093/hmg/ddag047","url":null,"abstract":"<p><p>Pathogenic variants in the autoimmune regulator gene (AIRE) cause Autoimmune polyendocrine syndrome type 1 (APS-1). The majority of disease-causing variants are inherited recessively, while several heterozygous AIRE variants have been reported in the literature as having dominant-negative or partially inhibitory effects. Additionally, some heterozygous AIRE variants have been implicated in milder and more common autoimmune phenotypes in disease cohort studies. The contribution of these variants to disease risk in unselected populations has not been assessed at scale. We aimed to investigate the prevalence and phenotypic impact of rare coding variants in AIRE in 449 075 participants from the UK Biobank (UKB). A literature review identified 25 rare heterozygous AIRE variants previously reported in association with autoimmunity, including variants described as dominant-negative or partially inhibitory, 13 of which were observed in UKB, collectively carried by 2123 participants. Filtering and annotation of rare coding AIRE variants identified a further 180 rare coding AIRE variants in 1934 UKB participants. Phenotype association analysis revealed no significant associations between rare heterozygous AIRE variants previously reported in association with autoimmunity and APS-1-associated traits after multiple-testing correction. Similarly, no statistically significant associations were observed for other heterozygous carriers of missense variants, frameshift/protein-truncating variants, or domain-specific groupings. These findings are consistent with a predominantly recessive model of AIRE-associated disease and indicate limited penetrance of rare heterozygous variants in the UKB population. Our work highlights the need for cautious interpretation of heterozygous AIRE variants in clinical settings.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The abnormal C-terminus caused by DVL1 variants impacts Robinow syndrome phenotypes.","authors":"Shruti S Tophkhane, Gamze Akarsu, Sarah J Gignac, Xinyi Xie, Katherine Fu, Esther M Verheyen, Joy M Richman","doi":"10.1093/hmg/ddag053","DOIUrl":"10.1093/hmg/ddag053","url":null,"abstract":"<p><p>Robinow Syndrome is a genetically heterogeneous, rare skeletal disorder characterized by craniofacial and limb defects. All 7 causative genes lie in the Wingless-related Integration site-1 (WNT) pathway. Here we study the pathogenesis of DVL1 (Dishevelled 1), the most commonly affected gene, where variants cause a frameshift that replaces the C terminus with a novel peptide. We compared phenotypes caused by DVL11519ΔT to the effects of wtDVL1 or DVL1 with a stop codon at position 1519. Misexpression of DVL11519ΔT in chicken embryos with an avian retrovirus, leads to increased width of the frontonasal mass similar to the facial phenotype in RS. Ultimately skeletogenesis is inhibited, which was verified in primary cultures of frontonasal mass mesenchyme. In luciferase assays carried out in facial mesenchyme, wtDVL1 activated canonical and JNK-PCP WNT signalling whereas the DVL11519* and the DVL11519ΔT variant had significantly lower signaling activity. These data confirm that the C-terminus plays an important role in WNT signal transduction and skeletogenesis. We also determined that there is mislocalization of the protein expressed from DVL11519ΔT in the nucleus while the other two constructs were expressed in the cytoplasm. Nuclear expression of DVL1 may alter transcription in RS. In complementary Drosophila experiments using a variety of readouts, only the DVL11519ΔT variant and not the 1519* impacted morphogenesis and signaling. This is the first study to show that the novel C-terminus of DVL1 is sufficient to interfere with the function of DVL1 protein expressed from the normal allele in heterozygous, autosomal dominant RS.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 14","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal myogenesis chromatin state and CpG from the open alliance markers and their intersection with adult muscle and gastrointestinal genetics.","authors":"Xi Cheng, Cuipei Wu, Xiaohe Yang, Rui Liu","doi":"10.1093/hmg/ddag062","DOIUrl":"https://doi.org/10.1093/hmg/ddag062","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic inheritance links fetal chromatin organization and CpG methylation to lifelong tissue phenotypes. We tested the Fetal Chromatin-CpG Developmental Blueprint (FCCD-B) model, proposing that fetal chromatin states shaped by maternal nutrient and transcription factor networks establish regulatory programs preserved in adult traits.</p><p><strong>Methods: </strong>We integrated 21 970 fetal single-cell transcriptomes with chromatin accessibility data, including 130 myogenic cells. Adult GWAS datasets included 1614 appendicular lean mass (ALM) loci and 445 grip strength loci. Fine-mapping, colocalization, and gene regulatory networks were inferred using GRNBoost2, Enformer, and Basenji, alongside virtual-cell simulations of nutrient and stress perturbations.</p><p><strong>Results: </strong>ALM and grip strength showed strong genetic correlation (rg = 0.49; Z = 26). Fine-mapping identified 1355 high-confidence ALM loci (median PIP = 0.91). A total of 2935 shared GWAS-eQTL variants overlapped fetal chromatin, with 70-88% accessibility preserved in endothelial and cardiomyocyte lineages. A SMAD3-centered TGF-β network (50 targets) was identified. Simulations showed that vitamin D, folate, and oxidative stress increased myofibril index (+0.141), epithelial regeneration (+0.035), and combined effects (+0.147).</p><p><strong>Conclusion: </strong>Persistent fetal chromatin and CpG architectures encode regulatory programs linking maternal environment to adult phenotypes, supporting the FCCD-B model as a predictive framework for developmental epigenetics.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 14","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A functional framework in patient fibroblasts informs ATP7A variant pathogenicity and identifies p.Q990P as a novel cause of distal motor neuropathy.","authors":"Gonzalo Perez-Siles, Bianca R Grosz, Melina Ellis, Jonathan Baets, Ataf Sabir, Mary O'Driscoll, Rita Horvath, Kleopas A Kleopa, Sharon La Fontaine, Pontus Gourdon, Steve Vucic, Marina L Kennerson","doi":"10.1093/hmg/ddag061","DOIUrl":"10.1093/hmg/ddag061","url":null,"abstract":"<p><p>ATP7A is a P-type ATPase copper transporter and a central component of the intracellular network to maintain copper (Cu) homeostasis, trafficking between the trans-Golgi network (TGN) and the cell periphery in response to intracellular Cu levels. Pathogenic ATP7A variants cause Menkes disease (MNK), occipital horn syndrome (OHS) and X-linked distal hereditary motor neuropathy (HMNX), with the clinical severity inversely related to residual ATP7A function. In MNK and OHS, variants result in loss of ATP7A function due to absent (MNK) or markedly reduced (OHS) protein levels, leading to abolished ATP7A trafficking and/or impaired Cu transport capacity. HMNX-associated variants are thought to retain partial Cu transport activity, although functional data remain limited. To date, three missense variants (p.T994I, p.P1386S, p.A991D) are established causes of HMNX, but the number of ATP7A variants reported in patients with a distal motor neuropathy phenotype is increasing, creating a need for functional assessment of variants of uncertain significance (VUS). We have developed a functional framework for evaluating HMNX-associated ATP7A variants. Using three patient fibroblast lines carrying the confirmed variants, we demonstrate reduced ATP7A TGN localization under low-Cu conditions and impaired capacity of these cell lines to maintain intracellular Cu levels. By applying these assays to five VUS (p.R703H, p.Y760C, p.A768G, p.Q990P, p.M1311V) identified in individuals from unsolved peripheral neuropathy families, we identify p.Q990P as a novel ATP7A variant in a patient with progressive peripheral motor neuropathy. This approach enables comparison of Cu trafficking and handling across ATP7A alleles, providing a functional framework to support diagnostic variant classification.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 14","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13345369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Heart is the most susceptible organ in an isogenic background to loss of function mutations in the mitochondrial metallochaperone SCO1.","authors":"","doi":"10.1093/hmg/ddag048","DOIUrl":"10.1093/hmg/ddag048","url":null,"abstract":"","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRPS22 variants alter mitochondrial ribosome assembly in patients with leukodystrophy, movement disorder and intellectual impairment.","authors":"Ruth I C Glasgow, Finn Lennartsson, Snjolaug Arnardottir, Dmitrii Igorevich Shiriaev, Sandrina P Correia, Marco Moedas, Lucía Peña-Pérez, Martin Paucar, Karin Naess, Helene Bruhn, Nicole Lesko, Rolf Wibom, Joanna Rorbach, Christoph Freyer, Anna Wedell, Sofia Ygberg, Erik A Eklund, Anna Wredenberg","doi":"10.1093/hmg/ddag042","DOIUrl":"10.1093/hmg/ddag042","url":null,"abstract":"<p><p>Mitochondrial diseases are clinically and genetically heterogeneous, often complicating diagnosis. Here, we describe four unrelated individuals with suspected mitochondrial disease who shared similar neuroimaging features, including bilateral symmetrical supra- and infratentorial white-matter abnormalities, together with variable movement disorders and intellectual impairment. Whole-genome sequencing identified the same homozygous MRPS22 variant (c.798_799delinsTA) in all four patients. MRPS22 encodes a component of the mitochondrial small ribosomal subunit (mtSSU). Functional studies in patient-derived fibroblasts showed impaired mitoribosome assembly and reduced de novo mitochondrial translation. Despite largely preserved steady-state levels of OXPHOS proteins, respiratory chain analysis identified a mild, isolated complex I deficiency. Proteomic profiling revealed reduced levels of mitochondrial ribosomal proteins and dysregulation of mitochondrial translation pathways. In line with the proteomic findings, RNA sequencing of fibroblasts from three patients revealed a distinct transcriptional signature compared with controls, with mitochondrial translation emerging as the most affected pathway. Mitochondrial-encoded transcripts were decreased, whereas nuclear-encoded mitochondrial genes were generally increased. Structural modelling suggested that the variant disrupts key interactions important for mitoribosome stability. While previously reported MRPS22 variants have been associated with severe, often prenatal-onset disease, the individuals described here exhibited a milder phenotype, thereby expanding the clinical spectrum of MRPS22-related disorders. Together, these findings support the pathogenicity of this variant and highlight the value of integrated genomic and functional analyses in diagnosing mitochondrial disease.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":"35 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}