{"title":"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。","authors":"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","doi":"10.3389/fgene.2025.1527228","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>GAA</i>, <i>GALT</i>, <i>CYP1B1</i>, and <i>MEFV</i> were identified, exhibiting distinct regional patterns compared to previously reported variants in the Han Chinese population.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1527228"},"PeriodicalIF":2.8000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104066/pdf/","citationCount":"0","resultStr":"{\"title\":\"Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.\",\"authors\":\"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\",\"doi\":\"10.3389/fgene.2025.1527228\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>GAA</i>, <i>GALT</i>, <i>CYP1B1</i>, and <i>MEFV</i> were identified, exhibiting distinct regional patterns compared to previously reported variants in the Han Chinese population.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":12750,\"journal\":{\"name\":\"Frontiers in Genetics\",\"volume\":\"16 \",\"pages\":\"1527228\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-05-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104066/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fgene.2025.1527228\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fgene.2025.1527228","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.
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.
Frontiers in GeneticsBiochemistry, 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.
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