Yan Li

Bio: Yan Li is an academic researcher from University of Chicago. The author has contributed to research in topics: Medicine & Population. The author has an hindex of 23, co-authored 71 publications receiving 4254 citations. Previous affiliations of Yan Li include University of Illinois at Urbana–Champaign & Nanjing Agricultural University.

Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines

Abstract: Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases, genome-wide association (GWA) studies have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available, because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly self-fertilizing model plant known to harbour considerable genetic variation for many adaptively important traits. Our results are dramatically different from those of human GWA studies, in that we identify many common alleles of major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true associations from false. However, a-priori candidates are significantly over-represented among these associations as well, making many of them excellent candidates for follow-up experiments. Our study demonstrates the feasibility of GWA studies in A. thaliana and suggests that the approach will be appropriate for many other organisms.

The scale of population structure in Arabidopsis thaliana.

Abstract: The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales.

A Coastal Cline in Sodium Accumulation in Arabidopsis thaliana Is Driven by Natural Variation of the Sodium Transporter AtHKT1;1

Abstract: The genetic model plant Arabidopsis thaliana, like many plant species, experiences a range of edaphic conditions across its natural habitat. Such heterogeneity may drive local adaptation, though the molecular genetic basis remains elusive. Here, we describe a study in which we used genome-wide association mapping, genetic complementation, and gene expression studies to identify cis-regulatory expression level polymorphisms at the AtHKT1;1 locus, encoding a known sodium (Na+) transporter, as being a major factor controlling natural variation in leaf Na+ accumulation capacity across the global A. thaliana population. A weak allele of AtHKT1;1 that drives elevated leaf Na+ in this population has been previously linked to elevated salinity tolerance. Inspection of the geographical distribution of this allele revealed its significant enrichment in populations associated with the coast and saline soils in Europe. The fixation of this weak AtHKT1;1 allele in these populations is genetic evidence supporting local adaptation to these potentially saline impacted environments.

Association mapping of local climate-sensitive quantitative trait loci in Arabidopsis thaliana.

Abstract: Flowering time (FT) is the developmental transition coupling an internal genetic program with external local and seasonal climate cues The genetic loci sensitive to predictable environmental signals underlie local adaptation We dissected natural variation in FT across a new global diversity set of 473 unique accessions, with >12,000 plants across two seasonal plantings in each of two simulated local climates, Spain and Sweden Genome-wide association mapping was carried out with 213,497 SNPs A total of 12 FT candidate quantitative trait loci (QTL) were fine-mapped in two independent studies, including 4 located within ±10 kb of previously cloned FT alleles and 8 novel loci All QTL show sensitivity to planting season and/or simulated location in a multi-QTL mixed model Alleles at four QTL were significantly correlated with latitude of origin, implying past selection for faster flowering in southern locations Finally, maximum seed yield was observed at an optimal FT unique to each season and location, with four FT QTL directly controlling yield Our results suggest that these major, environmentally sensitive FT QTL play an important role in spatial and temporal adaptation

Resistance to the Soybean Aphid in Soybean Germplasm

Abstract: With an efficient greenhouse screening method, the first resistance to the soybean aphid (Aphis glycines Matsumura) was found in cultivated soybean [Glycine max (L.) Merr.] germplasm. No resistance was found in 1425 current North American soybean cultivars, 106 Maturity Group (MG) 000 through VII Asian cultivars, and in a set of 11 ‘Clark’ isolines possessing different pubescence traits. Dense pubescence did not provide protection against the soybean aphid. Resistance was discovered and established in three ancestors of North American genotypes: ‘Dowling’, ‘Jackson’, and PI 71506. Expression of resistance in those genotypes was characterized in choice and nonchoice tests. In choice tests, significantly fewer aphids occurred on Dowling, Jackson, and PI 71506 plants compared with susceptible cultivars (P = 0.05). Aphid populations did not develop on Dowling and Jackson in nonchoice tests, indicating that there was a negative impact on aphid fecundity on those cultivars. That evidence combined with observations of aphid mortality on those cultivars suggested that antibiosis-type resistance contributed to the expression of resistance. Possible donors of resistance to Dowling and Jackson were identified. In nonchoice tests, population development on PI 71506 was not significantly different from development on susceptible cultivars, indicating that antixenosis was more important in that genotype. Resistance was expressed in all plant stages. Dowling provided season-long protection against aphids equal to the use of the systemic insecticide imidacloprid {1-[(6-Chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine} in a field test. Four other germplasm accessions, ‘Sugao Zarai’, ‘Sato’, ‘T260H’, and PI 230977, had levels of resistance not significantly different from Dowling, Jackson, and PI 71506 in a choice test (P = 0.05).

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Genome-wide association studies of 14 agronomic traits in rice landraces

Abstract: Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ∼ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ∼ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.

Development of High-Density Genetic Maps for Barley and Wheat Using a Novel Two-Enzyme Genotyping-by-Sequencing Approach

Abstract: Advancements in next-generation sequencing technology have enabled whole genome re-sequencing in many species providing unprecedented discovery and characterization of molecular polymorphisms. There are limitations, however, to next-generation sequencing approaches for species with large complex genomes such as barley and wheat. Genotyping-by-sequencing (GBS) has been developed as a tool for association studies and genomics-assisted breeding in a range of species including those with complex genomes. GBS uses restriction enzymes for targeted complexity reduction followed by multiplex sequencing to produce high-quality polymorphism data at a relatively low per sample cost. Here we present a GBS approach for species that currently lack a reference genome sequence. We developed a novel two-enzyme GBS protocol and genotyped bi-parental barley and wheat populations to develop a genetically anchored reference map of identified SNPs and tags. We were able to map over 34,000 SNPs and 240,000 tags onto the Oregon Wolfe Barley reference map, and 20,000 SNPs and 367,000 tags on the Synthetic W9784 × Opata85 (SynOpDH) wheat reference map. To further evaluate GBS in wheat, we also constructed a de novo genetic map using only SNP markers from the GBS data. The GBS approach presented here provides a powerful method of developing high-density markers in species without a sequenced genome while providing valuable tools for anchoring and ordering physical maps and whole-genome shotgun sequence. Development of the sequenced reference genome(s) will in turn increase the utility of GBS data enabling physical mapping of genes and haplotype imputation of missing data. Finally, as a result of low per-sample costs, GBS will have broad application in genomics-assisted plant breeding programs.