Gene expression trajectories aiding the unveiling of phenotypic similarities in developmental disorders: insights from human-mouse comparative analysis

doi:10.21037/pm-23-27

科研成果详情

题名	Gene expression trajectories aiding the unveiling of phenotypic similarities in developmental disorders: insights from human-mouse comparative analysis
作者	Jiang, Xinyi1,2,3; Tao, Jiahong1,2,3; Zhang, Yanyan1,2,3; Lin, Zhenlang1,2; Wang, Yaqiong 3; Zhou, Wenhao 1,2,3
发表日期	2023-11-30
发表期刊	PEDIATRIC MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Developmental disorders mouse models gene expression trajectories phenotypic similarity
其他关键词	CANDIDATE GENES ; SCHIZOPHRENIA ; PATTERNS ; REVEALS ; DOSAGE ; SLEEP
摘要	Background: Developmental disorders result from impaired prenatal development, often attributed to deleterious genetic variations. Knockout mouse models are critical tools in diseases research, but null mutations of orthologous genes in humans and mice often resulted in different phenotypes. As phenotypes are described during developmental processes, we explored the temporal patterns of gene expression trajectories during development. Methods: We utilized Spearman correlation analysis to compute the expression similarity of orthologous genes in temporal expression data of humans and mice. Gene list associated with developmental disorders was downloaded from the Developmental Disorders Genotype -to -Phenotype (DDG2P) database and classified according to the full spectrum of intolerance to loss -of -function (FUSIL) categorization. The phenotypic similarities of orthologous genes were quantified using Phenodigm scores derived from the calculations based on Human Phenotype Ontology (HPO) and Model Phenotype Ontology (MPO) terms. The phenotypic similarities of ionotropic glutamate receptors (iGluRs) genes with protein -truncating variants (PTVs) were computed as refined Phenodigm scores, utilizing manually curated profiles from the HPO terms and MPO terms. Results: This study investigated the expression trajectories of DDG2P genes and their association with phenotypic similarities between humans and mice. We observed that DDG2P genes showed more similar expression trajectories in major tissues compared to non-DDG2P genes. Additionally, in DDG2P genes, viable with phenotype (VP) genes with similar expression trajectories in the brain exhibited analogous phenotypes across humans and mice (autosomal dominant genes: Wilcoxon test: Z =11, P=0.02; autosomal recessive genes: Wilcoxon test: Z =9, P=0.003). To illustrate the feasibility of utilizing gene expression trajectory similarity to assist in inferring phenotypic similarity, we examined a gene family associated with neurodevelopmental disorder. Our findings suggest that similar expression trajectories of iGluRs genes in the brain and cerebellum could assist in predicting comparable neurological phenotypes across species. Conclusions: The gene expression trajectory offered a potential elucidation for the disparate phenotypes observed due to null mutations in humans and mice. Leveraging gene expression trajectories might enhance the precision in predicting candidate pathogenic genes.
出版者	AME PUBLISHING COMPANY
EISSN	2617-5428
卷号	6
DOI	10.21037/pm-23-27
页数	16
WOS类目	Pediatrics
WOS研究方向	Pediatrics
WOS记录号	WOS:001222054900007
收录类别	ESCI
通讯作者地址	[Zhou, Wenhao]Wenzhou Med Univ, Affiliated Hosp 2, Dept Neonatol, 109 Xueyuan Western Rd, Wenzhou 325000, Peoples R China. ; [Zhou, Wenhao]Wenzhou Med Univ, Yuying Childrens Hosp, 109 Xueyuan Western Rd, Wenzhou 325000, Peoples R China. ; [Wang, Yaqiong;Zhou, Wenhao]Fudan Univ, Ctr Mol Med, Natl Childrens Med Ctr, Childrens Hosp, 399 Wanyuan Rd, Shanghai 201102, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/213208
专题	附属第二医院_新生儿科第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Wang, Yaqiong; Zhou, Wenhao
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Neonatol, 109 Xueyuan Western Rd, Wenzhou 325000, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, 109 Xueyuan Western Rd, Wenzhou 325000, Peoples R China; 3.Fudan Univ, Ctr Mol Med, Natl Childrens Med Ctr, Childrens Hosp, 399 Wanyuan Rd, Shanghai 201102, Peoples R China
第一作者单位	附属第二医院_新生儿科; 第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	附属第二医院_新生儿科; 第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	附属第二医院_新生儿科
推荐引用方式 GB/T 7714	Jiang, Xinyi,Tao, Jiahong,Zhang, Yanyan,et al. Gene expression trajectories aiding the unveiling of phenotypic similarities in developmental disorders: insights from human-mouse comparative analysis[J]. PEDIATRIC MEDICINE,2023,6.
APA	Jiang, Xinyi, Tao, Jiahong, Zhang, Yanyan, Lin, Zhenlang, Wang, Yaqiong, & Zhou, Wenhao. (2023). Gene expression trajectories aiding the unveiling of phenotypic similarities in developmental disorders: insights from human-mouse comparative analysis. PEDIATRIC MEDICINE, 6.
MLA	Jiang, Xinyi,et al."Gene expression trajectories aiding the unveiling of phenotypic similarities in developmental disorders: insights from human-mouse comparative analysis".PEDIATRIC MEDICINE 6(2023).