candidate genes
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Author(s):  
Rongrong Ding ◽  
Zhanwei Zhuang ◽  
Yibin Qiu ◽  
Donglin Ruan ◽  
Jie Wu ◽  
...  

Abstract Backfat thickness (BFT) is complex and economically important traits in the pig industry, since it reflects fat deposition and can be used to measure the carcass lean meat percentage in pigs. In this study, all 6,550 pigs were genotyped using the Geneseek Porcine 50K SNP Chip to identify SNPs related to BFT and to search for candidate genes through genome-wide association analysis in two Duroc populations. In total, 80 SNPs, including 39 significant and 41 suggestive SNPs, and 6 QTLs were identified significantly associated with the BFT. In addition, 9 candidate genes, including a proven major gene MC4R, 3 important candidate genes (RYR1, HMGA1 and NUDT3) which were previously described as related to BFT, and 5 novel candidate genes (SIRT2, NKAIN2, AMH, SORCS1 and SORCS3) were found based on their potential functional roles in BFT. The functions of candidate genes and gene set enrichment analysis indicate that most important pathways are related to energy homeostasis and adipogenesis. Finally, our data suggests that most of the candidate genes can be directly used for genetic improvement through molecular markers, except that the MC4R gene has an antagonistic effect on growth rate and carcass lean meat percentage in breeding. Our results will advance our understanding of the complex genetic architecture of BFT traits, and laid the foundation for additional genetic studies to increase carcass lean meat percentage of pig through marker-assisted selection and/or genomic selection.


Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 214
Author(s):  
Qinghui Han ◽  
Qingxiang Zhu ◽  
Yao Shen ◽  
Michael Lee ◽  
Thomas Lübberstedt ◽  
...  

Chilling injury poses a serious threat to seed emergence of spring-sowing maize in China, which has become one of the main climatic limiting factors affecting maize production in China. It is of great significance to mine the key genes controlling low-temperature tolerance during seed germination and study their functions for breeding new maize varieties with strong low-temperature tolerance during germination. In this study, 176 lines of the intermated B73 × Mo17 (IBM) Syn10 doubled haploid (DH) population, which comprised 6618 bin markers, were used for QTL analysis of low-temperature germination ability. The results showed significant differences in germination related traits under optimum-temperature condition (25 °C) and low-temperature condition (10 °C) between two parental lines. In total, 13 QTLs were detected on all chromosomes, except for chromosome 5, 7, 10. Among them, seven QTLs formed five QTL clusters on chromosomes 1, 2, 3, 4, and 9 under the low-temperature condition, which suggested that there may be some genes regulating multiple germination traits at the same time. A total of 39 candidate genes were extracted from five QTL clusters based on the maize GDB under the low-temperature condition. To further screen candidate genes controlling low-temperature germination, RNA-Seq, in which RNA was extracted from the germination seeds of B73 and Mo17 at 10 °C, was conducted, and three B73 upregulated genes and five Mo17 upregulated genes were found by combined analysis of RNA-Seq and QTL located genes. Additionally, the variations of Zm00001d027976 (GLABRA2), Zm00001d007311 (bHLH transcription factor), and Zm00001d053703 (bZIP transcription factor) were found by comparison of amino sequence between B73 and Mo17. This study will provide a theoretical basis for marker-assisted breeding and lay a foundation for further revealing molecular mechanism of low-temperature germination tolerance in maize.


2022 ◽  
Vol 11 ◽  
Author(s):  
Lulu Wang ◽  
Dan Zeng ◽  
Qi Wang ◽  
Li Liu ◽  
Tao Lu ◽  
...  

Brain metastases represent a major cause of mortality among patients with breast cancer, and few effective targeted treatment options are currently available. Development of new biomarkers and therapeutic targets for breast cancer brain metastases (BCBM) is therefore urgently needed. In this study, we compared the gene expression profiles of the brain metastatic cell line MDA-MB-231-BR (231-BR) and its parental MDA-MB-231, and identified a total of 84 genes in the primary screening through a series of bioinformatic analyses, including construction of protein-protein interaction (PPI) networks by STRING database, identification of hub genes by applying of MCODE and Cytohubba algorithms, identification of leading-edge subsets of Gene Set Enrichment Analysis (GSEA), and identification of most up-regulated genes. Eight genes were identified as candidate genes due to their elevated expression in brain metastatic 231-BR cells and prognostic values in patients with BCBM. Then we knocked down the eight individual candidate genes in 231-BR cells and evaluated their impact on cell migration through a wound-healing assay, and four of them (KRT19, FKBP10, GSK3B and SPANXB1) were finally identified as key genes. Furthermore, the expression of individual key genes showed a correlation with the infiltration of major immune cells in the brain tumor microenvironment (TME) as analyzed by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), suggesting possible roles of them in regulation of the tumor immune response in TME. Therefore, the present work may provide new potential biomarkers for BCBM. Additionally, using GSEA, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis, we determined the top enriched cellular functions or pathways in 231-BR cells, which may help better understand the biology governing the development and progression of BCBM.


2022 ◽  
Author(s):  
Tianxiang Liu ◽  
Yulin Sun ◽  
Chao Ma ◽  
Wenhui Jiang ◽  
Hongqi Wu ◽  
...  

Abstract Bread wheat (Triticum aestivum L.) is an important source of nutrients for humans. Therefore, improvement of its yields is essential to feed the increasing world population. The tri-pistil (TRP) trait in wheat has a high potential for increasing yields. We obtained a pure tri-pistil wheat line, 4045, and evaluated its morphological properties. The 4045 wheat line stably produced three independently inherited pistils, which led to 1-3 grains in each floret. Among the three pistils, two lately emerged pistils initiated at late anther primordia stage to early tetrads stage. Genetic analysis revealed that there were TRP penetrance variations among the 11 F1 populations of 4045. Fine mapping narrowed the single dominant TRP locus to a 97.3 kb region, containing two candidate genes, on the 2DL chromosome. However, further gene sequence, functional as well as comparative genomic analyses ruled out the only two candidate genes. Therefore, TRP is high-likely a unique gain-of-function mutation that does not exist in normal wheat genome. Transcriptome analysis of floral homeotic genes revealed that expressions of the C-class TaAG-2s, which are essential for carpel specification, significantly increased in 4045, implying that TaAG-2s have played important roles in TRP-regulated tri-pistil formation. This study highlights that TRP leads to a precisely regulated pistil number increase (PRPNI) mutations and proposed a regulatory model of PRPNI pistil architecture. PRPNI offers a novel abnormal pistil development resource for research of floral architectures and potential on crop yield improvement.


2022 ◽  
Vol 15 ◽  
Author(s):  
Chloe J. Jordan ◽  
Zheng-Xiong Xi

Understanding risk factors for substance use disorders (SUD) can facilitate medication development for SUD treatment. While a rich literature exists discussing environmental factors that influence SUD, fewer articles have focused on genetic factors that convey vulnerability to drug use. Methods to identify SUD risk genes include Genome-Wide Association Studies (GWAS) and transgenic approaches. GWAS have identified hundreds of gene variants or single nucleotide polymorphisms (SNPs). However, few genes identified by GWAS have been verified by clinical or preclinical studies. In contrast, significant progress has been made in transgenic approaches to identify risk genes for SUD. In this article, we review recent progress in identifying candidate genes contributing to drug use and addiction using transgenic approaches. A central hypothesis is if a particular gene variant (e.g., resulting in reduction or deletion of a protein) is associated with increases in drug self-administration or relapse to drug seeking, this gene variant may be considered a risk factor for drug use and addiction. Accordingly, we identified several candidate genes such as those that encode dopamine D2 and D3 receptors, mGluR2, M4 muscarinic acetylcholine receptors, and α5 nicotinic acetylcholine receptors, which appear to meet the risk-gene criteria when their expression is decreased. Here, we describe the role of these receptors in drug reward and addiction, and then summarize major findings from the gene-knockout mice or rats in animal models of addiction. Lastly, we briefly discuss future research directions in identifying addiction-related risk genes and in risk gene-based medication development for the treatment of addiction.


Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Weihong Li ◽  
Shixiang Zhou ◽  
Meng Jia ◽  
Xiaoxin Li ◽  
Lin Li ◽  
...  

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.


2022 ◽  
Vol 12 ◽  
Author(s):  
Lihua Wang ◽  
Yanlong Liu ◽  
Li Gao ◽  
Xiaocui Yang ◽  
Xu Zhang ◽  
...  

Genetic dissection of forage yield traits is critical to the development of sorghum as a forage crop. In the present study, association mapping was performed with 85,585 SNP markers on four forage yield traits, namely plant height (PH), tiller number (TN), stem diameter (SD), and fresh weight per plant (FW) among 245 sorghum accessions evaluated in four environments. A total of 338 SNPs or quantitative trait nucleotides (QTNs) were associated with the four traits, and 21 of these QTNs were detected in at least two environments, including four QTNs for PH, ten for TN, six for SD, and one for FW. To identify candidate genes, dynamic transcriptome expression profiling was performed at four stages of sorghum development. One hundred and six differentially expressed genes (DEGs) that were enriched in hormone signal transduction pathways were found in all stages. Weighted gene correlation network analysis for PH and SD indicated that eight modules were significantly correlated with PH and that three modules were significantly correlated with SD. The blue module had the highest positive correlation with PH and SD, and the turquoise module had the highest negative correlation with PH and SD. Eight candidate genes were identified through the integration of genome-wide association studies (GWAS) and RNA sequencing. Sobic.004G143900, an indole-3-glycerol phosphate synthase gene that is involved in indoleacetic acid biosynthesis, was down-regulated as sorghum plants grew in height and was identified in the blue module, and Sobic.003G375100, an SD candidate gene, encoded a DNA repair RAD52-like protein 1 that plays a critical role in DNA repair-linked cell cycle progression. These findings demonstrate that the integrative analysis of omics data is a promising approach to identify candidate genes for complex traits.


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