Biomedical subjects

Fusheng Wei

Publications and source records attributed to Fusheng Wei.

14 recordsLinked to original sources

PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗

PubMed2006

Uneven chromosome contraction and expansion in the maize genome.

Maize (Zea mays or corn), both a major food source and an important cytogenetic model, evolved from a tetraploid that arose about 4.8 million years ago (Mya). As a result, maize has extensive duplicated regions within its genome. We have sequenced the two copies of one such region, generating 7.8 Mb of sequence spanning 17.4 cM of the short arm of chromosome 1 and 6.6 Mb (25.6 cM) from the long arm of chromosome 9. Rice, which did not undergo a similar whole genome duplication event, has only one orthologous region (4.9 Mb) on the short arm of chromosome 3, and can be used as reference for the maize homoeologous regions. Alignment of the three regions allowed identification of syntenic blocks, and indicated that the maize regions have undergone differential contraction in genic and intergenic regions and expansion by the insertion of retrotransposable elements. Approximately 9% of the predicted genes in each duplicated region are completely missing in the rice genome, and almost 20% have moved to other genomic locations. Predicted genes within these regions tend to be larger in maize than in rice, primarily because of the presence of predicted genes in maize with larger introns. Interestingly, the general gene methylation patterns in the maize homoeologous regions do not appear to have changed with contraction or expansion of their chromosomes. In addition, no differences in methylation of single genes and tandemly repeated gene copies have been detected. These results, therefore, provide new insights into the diploidization of polyploid species.

Base Sequence↗

PubMed2006

Boron workers in China: exploring work and lifestyle factors related to boron exposure.

This article describes the lifestyle patterns of boron mining and processing workers (N=936) and a comparison group (N=251) in northeast China, and explores relationships between boron exposure and reproductive health. An English version of an interview guide addressing areas of work and lifestyle relevant to boron exposure and metabolism was developed by an occupational health research team, translated to Chinese, and translated back, for clarity. Modifications incorporated suggestions from a local community advisory board and boron industry workers; the translation-back translation process was reapplied, and cultural and semantic equivalence was attained. Results from the interviews showed more than 64% of workers and comparison group participants smoked tobacco and more than 92% reported exposure to environmental tobacco smoke. Boron workers and the comparison group varied in their food intake and alcohol consumption, but not in their smoking habits. Thirty-four percent of boron workers reported eating in the contaminated work area. Nearly all boron workers (99%) showered or bathed after work, although approximately 10% redressed in their contaminated clothes. Reproductive health outcomes were explored, including delayed pregnancy, multiple births, spontaneous miscarriages, induced abortions, stillbirths, and an unusual ratio of male to female offspring. Implications for occupational health nurses and recommendations for future research are provided.

Adult↗

PubMed2005

Sequence, annotation, and analysis of synteny between rice chromosome 3 and diverged grass species.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

Arabidopsis↗

PubMed2005

Whole-genome validation of high-information-content fingerprinting.

Fluorescent-based high-information-content fingerprinting (HICF) techniques have recently been developed for physical mapping. These techniques make use of automated capillary DNA sequencing instruments to enable both high-resolution and high-throughput fingerprinting. In this article, we report the construction of a whole-genome HICF FPC map for maize (Zea mays subsp. mays cv B73), using a variant of HICF in which a type IIS restriction enzyme is used to generate the fluorescently labeled fragments. The HICF maize map was constructed from the same three maize bacterial artificial chromosome libraries as previously used for the whole-genome agarose FPC map, providing a unique opportunity for direct comparison of the agarose and HICF methods; as a result, it was found that HICF has substantially greater sensitivity in forming contigs. An improved assembly procedure is also described that uses automatic end-merging of contigs to reduce the effects of contamination and repetitive bands. Several new features in FPC v7.2 are presented, including shared-memory multiprocessing, which allows dramatically faster assemblies, and automatic end-merging, which permits more accurate assemblies. It is further shown that sequenced clones may be digested in silico and located accurately on the HICF assembly, despite size deviations that prevent the precise prediction of experimental fingerprints. Finally, repetitive bands are isolated, and their effect on the assembly is studied.

DNA Fingerprinting↗

PubMed2005

The R1 resistance gene cluster contains three groups of independently evolving, type I R1 homologues and shows substantial structural variation among haplotypes of Solanum demissum.

Cultivated and wild potatoes contain a major disease-resistance cluster on the short arm of chromosome V, including the R1 resistance (R) gene against potato late blight. To explore the functional and evolutionary significance of clustering in the generation of novel disease-resistance genes, we constructed three approximately 1 Mb physical maps in the R1 gene region, one for each of the three genomes (haplotypes) of allohexaploid Solanum demissum, the wild potato progenitor of the R1 locus. Totals of 691, 919 and 559 kb were sequenced for each haplotype, and three distinct resistance-gene families were identified, one homologous to the potato R1 gene and two others homologous to either the Prf or the Bs4 R-gene of tomato. The regions with R1 homologues are highly divergent among the three haplotypes, in contrast to the conserved flanking non-resistance gene regions. The R1 locus shows dramatic variation in overall length and R1 homologue number among the three haplotypes. Sequence comparisons of the R1 homologues show that they form three distinct clades in a distance tree. Frequent sequence exchanges were detected among R1 homologues within each clade, but not among those in different clades. These frequent sequence exchanges homogenized the intron sequences of homologues within each clade, but did not homogenize the coding sequences. Our results suggest that the R1 homologues represent three independent groups of fast-evolving type I resistance genes, characterized by chimeric structures resulting from frequent sequence exchanges among group members. Such genes were first identified among clustered RGC2 genes in lettuce, where they were distinguished from slow-evolving type II R-genes. Our findings at the R1 locus in S. demissum may indicate that a common or similar mechanism underlies the previously reported differentiation of type I and type II R-genes and the differentiation of type I R-genes into distinct groups, identified here.

Chromosomes, Artificial, Bacterial↗

PubMed2004

Sequence composition and genome organization of maize.

Zea mays L. ssp. mays, or corn, one of the most important crops and a model for plant genetics, has a genome approximately 80% the size of the human genome. To gain global insight into the organization of its genome, we have sequenced the ends of large insert clones, yielding a cumulative length of one-eighth of the genome with a DNA sequence read every 6.2 kb, thereby describing a large percentage of the genes and transposable elements of maize in an unbiased approach. Based on the accumulative 307 Mb of sequence, repeat sequences occupy 58% and genic regions occupy 7.5%. A conservative estimate predicts approximately 59,000 genes, which is higher than in any other organism sequenced so far. Because the sequences are derived from bacterial artificial chromosome clones, which are ordered in overlapping bins, tagged genes are also ordered along continuous chromosomal segments. Based on this positional information, roughly one-third of the genes appear to consist of tandemly arrayed gene families. Although the ancestor of maize arose by tetraploidization, fewer than half of the genes appear to be present in two orthologous copies, indicating that the maize genome has undergone significant gene loss since the duplication event.

Chromosomes, Artificial, Bacterial↗

PubMed2004

Factor analysis of household factors: are they associated with respiratory conditions in Chinese children?

BACKGROUND: We explored methods to develop uncorrelated variables for epidemiological analysis models. They were used to examine associations between respiratory health outcomes and multiple household risk factors. METHODS: We analysed data collected in the Four Chinese Cities Study (FCCS) to examine health effects on prevalence rates of respiratory symptoms and illnesses in 7058 school children living in the four Chinese cities: Lanzhou, Chongqing, Wuhan, and Guangzhou. We used factor analysis approaches to reduce the number of the children's lifestyle/household variables and to develop new uncorrelated 'factor' variables. We used unconditional logistic regression models to examine associations between the factor variables and the respiratory health outcomes, while controlling for other covariates. RESULTS: Five factor variables were derived from 21 original variables: heating coal smoke, cooking coal smoke, socioeconomic status, ventilation, and environmental tobacco smoke (ETS) and parental asthma. We found that higher exposure to heating coal smoke was associated with higher reporting of cough with phlegm, wheeze, and asthma. Cooking coal smoke was not associated with any of the outcomes. Lower socioeconomic status was associated with lower reporting of persistent cough and bronchitis. Higher household ventilation was associated with lower reporting of persistent cough, persistent phlegm, cough with phlegm, bronchitis, and wheeze. Higher exposure to ETS and the presence of parental asthma were associated with higher reporting of persistent cough, persistent phlegm, cough with phlegm, bronchitis, wheeze, and asthma. CONCLUSIONS: Our study suggests that independent respiratory effects of exposure to indoor air pollution, heating coal smoke, and ETS may exist for the studied children.

Air Pollution, Indoor↗

PubMed2004

Using air pollution based community clusters to explore air pollution health effects in children.

To study respiratory health effects of long-term exposure to ambient air pollutant mixture, we observed 7058 school children 5-16 years of age living in the four Chinese cities of Lanzhou, Chongqing, Wuhan, and Guangzhou. These children were enrolled from elementary schools located in eight districts, one urban district and one suburban district in each of the above cities. Ambient levels of PM(2.5), PM(10-2.5), total suspended particles (TSP), SO(2), and NO(x) were measured in these districts from 1993 to 1996. Based on a cluster analysis of arithmetic mean concentrations of PM(2.5), PM(10-2.5), (TSP-PM(10)), SO(2), and NO(x), we classified these children into four ordinal categories of exposure to ambient air pollutant mixtures. We tested for exposure-response relationships using logistic regression models, controlling for relevant covariates. We observed monotonic, positive relationships of exposure to the pollutant mixture with prevalence rates of cough with phlegm and wheeze. Other outcomes were not associated with the exposure in a monotonic exposure-response pattern. Even so, odds ratios for cough, phlegm, bronchitis, and asthma in the higher exposure district clusters were all higher than in the lowest exposure district cluster. We found evidence that exposure to the pollutant mixtures had adverse effects on children living in the four Chinese cities.

Adolescent↗

PubMed2004

Exposure-response relationships between lifetime exposure to residential coal smoke and respiratory symptoms and illnesses in Chinese children.

Data collected in a large epidemiologic study were analyzed to examine respiratory health effects of residential coal use in 7058 school children living in the four Chinese cities of Chongqing, Guangzhou, Lanzhou, and Wuhan. A Scenario Evaluation Approach was used to develop two exposure variables, heating coal smoke and cooking coal smoke. Estimated lifetime exposures to heating coal smoke and cooking coal smoke were both classified into four-level ordinal scales, as follows: no reported exposure (control); lightly exposed; moderately exposed; and heavily exposed. Zero-one dummy variables were constructed for each exposure level other than the control level (total six variables). These variables were entered into the analytical model. We tested for exposure-response relationships using logistic regression models, while controlling for other relevant covariates, including an indicator variable of ambient air pollution levels. We observed monotonic and positive exposure-response relationships of exposure to heating coal smoke with modeled odds ratios (ORs) of phlegm, cough with phlegm, and bronchitis. Other health outcomes were not associated with such exposure in a monotonic exposure-response pattern. However, ORs for cough, wheeze, and asthma were all higher in the exposed groups than in the control group. We observed no consistent associations between cooking coal smoke and the examined health outcomes. We conclude that exposure to heating coal smoke could have adverse effects on children's respiratory symptoms and illnesses in these four Chinese cities.

Air Pollution, Indoor↗

PubMed2003

Powdery mildew-induced Mla mRNAs are alternatively spliced and contain multiple upstream open reading frames.

In barley (Hordeum vulgare), the Mla13 powdery mildew resistance gene confers Rar1-dependent, AvrMla13-specific resistance to Blumeria graminis f. sp. hordei (Bgh). We have identified cDNA and genomic copies of Mla13 and used this coiled-coil nucleotide-binding site leucine-rich repeat protein-encoding gene as a model for the regulation of host resistance to obligate biotrophic fungi in cereals. We demonstrate quantitatively that a rapid increase in the accumulation of Mla transcripts and transcripts of the Mla-signaling genes, Rar1 and Sgt1, is triggered between 16 and 20 h post inoculation, the same time frame that haustoria of avirulent Bgh make contact with the host cell plasma membrane. An abundance of Mla13 cDNAs revealed five classes of transcript leader regions containing two alternatively spliced introns and up to three upstream open reading frames (uORFs). Alternative splicing of introns in the transcript leader region results in a different number of uORFs and variability in the size of uORF2. These results indicate that regulation of Mla transcript accumulation is not constitutive and that induction is coordinately controlled by recognition-specific factors. The sudden increase in specific transcript levels could account for the rapid defense response phenotype conferred by Mla6 and Mla13.

Alternative Splicing↗

PubMed2002

Chapter one: exposure measurements.

Determining human exposure to suspended particulate concentrations requires measurements that quantify different particle properties in microenvironments where people live, work, and play. Particle mass, size, and chemical composition are important exposure variables, and these are typically measured with time-integrated samples on filters that are later submitted to laboratory analyses. This requires substantial sample handling, quality assurance, and data reduction. Newer technologies are being developed that allow in-situ, time-resolved measurements for mass, carbon, sulfate, nitrate, particle size, and other variables. These are large measurement systems that are more suitable for fixed monitoring sites than for personal applications. Human exposure studies need to be designed to accomplish specific objectives rather than to serve too many purposes. Resources need to be divided among study design, field sampling, laboratory analysis, quality assurance, data management, and data analysis phases. Many exposure projects allocated too little to the non-measurement activities.

Air Pollutants↗

PubMed2002

Genome dynamics and evolution of the Mla (powdery mildew) resistance locus in barley.

Genes that confer defense against pathogens often are clustered in the genome and evolve via diverse mechanisms. To evaluate the organization and content of a major defense gene complex in cereals, we determined the complete sequence of a 261-kb BAC contig from barley cv Morex that spans the Mla (powdery mildew) resistance locus. Among the 32 predicted genes on this contig, 15 are associated with plant defense responses; 6 of these are associated with defense responses to powdery mildew disease but function in different signaling pathways. The Mla region is organized as three gene-rich islands separated by two nested complexes of transposable elements and a 45-kb gene-poor region. A heterochromatic-like region is positioned directly proximal to Mla and is composed of a gene-poor core with 17 families of diverse tandem repeats that overlap a hypermethylated, but transcriptionally active, gene-dense island. Paleontology analysis of long terminal repeat retrotransposons indicates that the present Mla region evolved over a period of >7 million years through a variety of duplication, inversion, and transposon-insertion events. Sequence-based recombination estimates indicate that R genes positioned adjacent to nested long terminal repeat retrotransposons, such as Mla, do not favor recombination as a means of diversification. We present a model for the evolution of the Mla region that encompasses several emerging features of large cereal genomes.

DNA Methylation↗

PubMed2002

Children's respiratory morbidity prevalence in relation to air pollution in four Chinese cities.

We examined respiratory health effects of long-term exposure to ambient air pollution in 7,621 schoolchildren residing in eight districts of four Chinese cities. The four cities exhibited wide between-city and within-city gradients in ambient levels of four size fractions of particulate matter [less than or equal to 2.5 micro m in aerodynamic diameter (PM(2.5)), between 2.5 and 10 micro m (PM(10-2.5)), less than or equal to 10 micro m (PM(10)), and total suspended particulates (TSP)] and two gaseous pollutants (SO(2) and NO(x)). Informed consent and written responses to questionnaires about children's personal, residential, and family information, as well as their health histories and status, were obtained with the help of the parents and the school personnel. We used a two-stage regression approach in data analyses. In the first-stage logistic regressions, we obtained logits of district-specific prevalence of wheeze, asthma, bronchitis, hospitalization for respiratory diseases, persistent cough, and persistent phlegm, adjusted for covariates representing personal, household, and family parameters. Some of these covariates were found to be risk factors of children's respiratory health, including being younger in the study group, being male, having been breast-fed, sharing bedrooms, sharing beds, room being smoky during cooking, eye irritation during cooking, parental smoking, and a history of parental asthma. In several of the second-stage variance-weighted linear regressions, we examined associations between district-specific adjusted prevalence rates and district-specific ambient levels of each pollutant. We found positive associations between morbidity prevalence and outdoor levels of PM of all size fractions, but the association appeared to be stronger for coarse particles (PM(10-2.5)). The results also present some evidence that ambient levels of NO(x) and SO(2) were positively associated with children's respiratory symptoms, but the evidence for these two gaseous pollutants appeared to be weaker than that for the PM.

Adolescent↗