PDF(Pubmed)
Abstract：
Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset.
The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P.
We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16.
Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.
The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P.
We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16.
Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.
摘要：
非综合征性唇裂和/或腭裂（NSCL/P）具有多因素病因，其中遗传因素，基因-环境相互作用，随机因素，基因-基因相互作用，和亲源效应(POE)起关键作用。当等位基因的亲本起源差异地影响后代的表型时,POEs出现。这项研究的目的是使用全基因组数据集确定可以增加人类NSCL/P风险的POEs。
样本(来自加纳的174个案例-家长三重奏，埃塞俄比亚,和尼日利亚）纳入这项研究的是2019年发表的非洲唯一全基因组关联研究（GWAS）。使用Illumina多种族基因分型阵列v215070954A2（基因组构建GRCh37/hg19）的超过200万个多种族和非洲血统特异性单核苷酸多态性对个体DNA进行基因分型在遗传性疾病研究中心。经过质量控制检查，PLINK用于使用NSCL/P的合并亚表型进行POE分析。
我们在6号染色体上的主要组织相容性复合物1类基因座的1兆碱基对窗口的一组基因中观察到POEs的可能提示，以及在包含候选基因的其他基因座，例如ASB18，ANKEF1，AGAP1，GABRD，帽子,CCT7,DNMT3A,EPHA7,FOXO3,lncRNAs,microRNA,反义RNA,ZNRD1,ZFAT,ZBTB16
我们的研究结果表明，某些基因座可能会通过POEs增加NSCL/P的风险。需要进一步的研究来确认这些提示位点在NSCL/P病因学中的应用。
样本(来自加纳的174个案例-家长三重奏，埃塞俄比亚,和尼日利亚）纳入这项研究的是2019年发表的非洲唯一全基因组关联研究（GWAS）。使用Illumina多种族基因分型阵列v215070954A2（基因组构建GRCh37/hg19）的超过200万个多种族和非洲血统特异性单核苷酸多态性对个体DNA进行基因分型在遗传性疾病研究中心。经过质量控制检查，PLINK用于使用NSCL/P的合并亚表型进行POE分析。
我们在6号染色体上的主要组织相容性复合物1类基因座的1兆碱基对窗口的一组基因中观察到POEs的可能提示，以及在包含候选基因的其他基因座，例如ASB18，ANKEF1，AGAP1，GABRD，帽子,CCT7,DNMT3A,EPHA7,FOXO3,lncRNAs,microRNA,反义RNA,ZNRD1,ZFAT,ZBTB16
我们的研究结果表明，某些基因座可能会通过POEs增加NSCL/P的风险。需要进一步的研究来确认这些提示位点在NSCL/P病因学中的应用。
