全基因组扫描在撒哈拉以南非洲非综合征性唇裂和/或腭裂（CL/P）队列中亲源性效应。

Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P).

机构信息

Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

98764School of Medicine and Dentistry, 260806Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

出版信息

Cleft Palate Craniofac J. 2022 Jul;59(7):841-851. doi: 10.1177/10556656211036316. Epub 2021 Aug 12.

DOI:10.1177/10556656211036316

PMID:34382870

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9884465/

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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 , , , , , , , , , lncRNAs, microRNA, antisense RNAs, , , and .

CONCLUSION

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

目的

非综合征性唇裂和/或腭裂（NSCL/P）具有多因素病因，遗传因素、基因-环境相互作用、随机因素、基因-基因相互作用和母源效应（POE）起着重要作用。当等位基因的亲本来源对后代的表型产生不同影响时，就会出现 POE。本研究的目的是使用全基因组数据集来识别可能增加人类 NSCL/P 风险的 POE。

方法

本研究的样本（来自加纳、埃塞俄比亚和尼日利亚的 174 个病例-父母三体型）来自于 2019 年发表的仅非洲全基因组关联研究（GWAS）。使用 Illumina Multi-Ethnic Genotyping Array v2 15070954 A2（基因组构建 GRCh37/hg19）上超过 200 万个多民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，该研究在遗传性疾病研究中心进行。经过质量控制检查后，使用 PLINK 对 NSCL/P 的 pooled subphenotypes 进行 POE 分析。