Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-05-12 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1527228

Danhua Guo, Nani Zhou, Qianqian He, Na Lin, Shuqiong He, Deqin He, Yifang Dai, Ying Li, Xuemei Chen, Hailong Huang, Jia Jia, Hua Cao, Liangpu Xu

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引用次数: 0

Abstract

Background: This pilot study aimed to characterize the regional distribution of genetic variants associated with autosomal recessive and X-linked recessive (AR/XLR) conditions in Fujian Province, Southeast China, to inform the development of targeted carrier screening programs.

Methods: An expanded carrier screening (ECS) panel utilizing next-generation sequencing (NGS) technology was designed to analyze 332 genes associated with 343 AR/XLR conditions. The panel was applied to 440 samples obtained from individuals in Fujian Province. Single nucleotide variants and copy number variations (CNVs) were identified and analyzed using a multidimensional approach that incorporated demographic characteristics, carrier frequencies, and the genetic burden of AR/XLR diseases.

Results: A total of 511 variants were detected among the 440 participants, including 43 CNVs (8.41%), affecting 133 genes associated with 123 conditions. The mean number of pathogenic or likely pathogenic variants per sample was 1.16. The highest genetic burden was observed in couples seeking medically assisted reproduction (MAR group), who had histories of fetal loss, second- or third-trimester abnormalities, or postnatal abnormalities. In clinical settings, the percentage of at-risk couples (ARCs) was 6.36% (n = 14), involving seven conditions, with no statistically significant difference in ARC incidence between couples undergoing genetic screening (GS group) and the MAR group. The cumulative carrier rate for 28 genes was ≥1/100. Recurrent variants in GAA, GALT, CYP1B1, and MEFV were identified, exhibiting distinct regional patterns compared to previously reported variants in the Han Chinese population.

Conclusion: NGS-based ECS demonstrates significant potential for assessing the genetic burden of AR/XLR conditions and identifying ARCs in Fujian Province. However, before integrating ECS into regional public health initiatives, the development of a region-specific, curated disease panel is necessary to optimize screening efficacy and clinical utility.

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扩大携带者筛选中遗传变异的区域模式：中国福建省的下一代测序试点研究。

背景：本初步研究旨在了解福建省常染色体隐性遗传和x连锁隐性遗传（AR/XLR）相关遗传变异的区域分布，为制定有针对性的携带者筛查计划提供信息。方法：利用新一代测序（NGS）技术设计扩展载体筛选（ECS）面板，分析343例AR/XLR相关的332个基因。该面板应用于从福建省个人获得的440个样本。使用多维方法识别和分析单核苷酸变异和拷贝数变异（CNVs），该方法包括AR/XLR疾病的人口统计学特征、携带者频率和遗传负担。结果：440名参与者共检测到511个变异，包括43个CNVs(8.41%)，影响133个与123种疾病相关的基因。每个样本的致病或可能致病变异的平均数量为1.16。在寻求医学辅助生殖（MAR组）的夫妇中，有流产史、妊娠中期或晚期异常或产后异常的人，遗传负担最高。在临床环境中，高危夫妇（ARC）的比例为6.36% (n = 14)，涉及7种情况，接受遗传筛查的夫妇（GS组）和MAR组之间的ARC发病率无统计学差异。28个基因的累积携带率≥1/100。GAA、GALT、CYP1B1和MEFV的复发变异被确定，与之前报道的汉族人群变异相比，表现出不同的区域模式。结论：基于ngs的ECS在福建省AR/XLR遗传负担评估和ARCs鉴定方面具有重要潜力。然而，在将ECS纳入区域公共卫生举措之前，有必要建立一个区域特异性的、精心策划的疾病小组，以优化筛查效果和临床效用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.