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利用全外显子组测序在沙特家族中鉴定导致非综合征性口腔面裂的致病变异体。

Identification of Causative Variants Contributing to Nonsyndromic Orofacial Clefts Using Whole-Exome Sequencing in a Saudi Family.

机构信息

Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.

Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Genet Test Mol Biomarkers. 2020 Nov;24(11):723-731. doi: 10.1089/gtmb.2019.0233. Epub 2020 Oct 29.


DOI:10.1089/gtmb.2019.0233
PMID:33121284
Abstract

Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial malformations observed across the globe. They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and palate. To identify the potential candidate genes contributing to polygenic diseases such as NSOFC, linkage analyses, genome-wide association studies, and genomic rearrangements can be used. Genomic analyses, based on massively parallel next-generation sequencing technologies, play a vital role in deciphering the genetic bases of NSOFCs. In this study, whole exome sequencing was employed to detect genes that likely contributed to the NSOFC phenotype in a consanguineous Saudi family. The exome analysis revealed (rs35320960) as one potential candidate gene that is involved in bone differentiation. The gene (rs199996172), which plays a crucial role in ribosome biogenesis, also passed all filters to serve as a candidate gene for NSOFC in this family. Rare variants are situated within the 5' UTR of these two genes. The study suggests that rare variants in and may be associated with NSOFC disease etiology.

摘要

非综合征性口面裂(NSOFC)是全球最常见的颅面畸形。它们分为三种类型:(a)腭裂,(b)唇裂,和(c)唇裂和腭裂。为了鉴定多基因疾病(如 NSOFC)的潜在候选基因,可采用连锁分析、全基因组关联研究和基因组重排。基于大规模平行下一代测序技术的基因组分析,在解析 NSOFC 的遗传基础方面起着至关重要的作用。在这项研究中,对一个沙特裔的近亲家族进行了全外显子组测序,以检测可能导致 NSOFC 表型的基因。外显子组分析发现(rs35320960)是一个可能参与骨分化的候选基因。(rs199996172)基因在核糖体生物发生中起着至关重要的作用,也通过了所有的筛选,成为该家族 NSOFC 的候选基因。这两个基因的罕见变异位于 5'UTR 内。该研究表明,这两个基因中的罕见变异可能与 NSOFC 疾病的病因有关。

相似文献

[1]
Identification of Causative Variants Contributing to Nonsyndromic Orofacial Clefts Using Whole-Exome Sequencing in a Saudi Family.

Genet Test Mol Biomarkers. 2020-11

[2]
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J Dent Res. 2022-4

[3]
Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

J Dent Res. 2016-10

[4]
Copy Number Changes Identified Using Whole Exome Sequencing in Nonsyndromic Cleft Lip and Palate in a Honduran Population.

Birth Defects Res. 2017-7-27

[5]
Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients.

Genet Test Mol Biomarkers. 2019-1

[6]
Exome sequencing provides additional evidence for the involvement of ARHGAP29 in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate.

Birth Defects Res. 2017-1-20

[7]
Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes.

J Med Genet. 2018-3-2

[8]
Using Whole Exome Sequencing to Identify Candidate Genes With Rare Variants In Nonsyndromic Cleft Lip and Palate.

Genet Epidemiol. 2016-7

[9]
A Comprehensive Genetic Analysis of Slovenian Families with Multiple Cases of Orofacial Clefts Reveals Novel Variants in the Genes , , and .

Int J Mol Sci. 2023-2-21

[10]
The Role of Noncoding Genetic Variation in Isolated Orofacial Clefts.

J Dent Res. 2017-10

引用本文的文献

[1]
Comparative RNA-Seq analysis of differentially expressed genes in the sertoli cells of yak and cattle-yak.

BMC Vet Res. 2025-2-22

[2]
Assessment of non-syndromic orofacial cleft severity and associated environmental factors in Saudi Arabia: A cross-sectional study.

Saudi Dent J. 2024-3

[3]
Parents and Provider Perspectives on the Return of Genomic Findings for Cleft Families in Africa.

AJOB Empir Bioeth. 2024

[4]
Incidence of non-syndromic orofacial cleft during the COVID-19 pandemic in Saudi Arabia.

BMC Public Health. 2023-12-19

[5]
COVID-19 related risk factors and their association with non-syndromic orofacial clefts in five Arab countries: a case-control study.

BMC Oral Health. 2023-4-28

[6]
Damaging Mutations in Contribute to Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate.

Cleft Palate Craniofac J. 2024-4

[7]
Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.

Sci Rep. 2022-7-11

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