Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians
Abstract Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians. Materials and meth...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02279-9 |
| _version_ | 1811335454161633280 |
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| author | Qi Ni Xiang Chen Ping Zhang Lin Yang Yulan Lu Feifan Xiao Bingbing Wu Huijun Wang Wenhao Zhou Xinran Dong |
| author_facet | Qi Ni Xiang Chen Ping Zhang Lin Yang Yulan Lu Feifan Xiao Bingbing Wu Huijun Wang Wenhao Zhou Xinran Dong |
| author_sort | Qi Ni |
| collection | DOAJ |
| description | Abstract Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians. Materials and methods We reviewed 30,951 exome-sequencing samples, including 20,909 pediatric patient samples and 10,042 parent samples, from Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System (CCGT). After the in-lab filtration process, 477 candidate variants of CFTR gene were left and 53 variants were manually curated as pathogenic/likely-pathogenic (P/LP). These P/LP variants were adopted to estimate CF prevalence in three methods: the carrier frequency method, the permutation-combinations method and the Bayesian framework method. Allele frequencies of the 477 CFTR variants were compared with non-Finland European (NFE) and East Asian (EAS) from gnomAD database. To investigate the haplotype structure difference of CFTR, another 2067 whole-genome-sequencing samples from CCGT and 195 NFE from 1000 genome project were analyzed by Shapeit4 software. Result With the 53 manually curated P/LP variants in CFTR gene, we excluded individuals identified or suspected with CF and their parents in our cohorts and estimated the Chinese CF prevalence is approximately 1/128,434. Only 21 (39.6%) of the 53 variants were included in Caucasian specific CF screening panels, resulting in significantly under-estimation of CF prevalence in our children cohort (1/143,171 vs. 1/1,387,395, P = 5e−24) and parent’s cohort (1/110,127 vs. 1/872,437, P = 7e−10). The allele frequencies of six pathogenic variants (G970D, D979A, M469V, G622D, L88X, 1898+5G->T) were significantly higher in our cohorts compared with gnomAD-NFE population (all P-value < 0.1). Haplotype analysis showed more haplotype diversity in Chinese compared to Caucasians. In addition, G970D and F508del were founder mutation of Chinese and Caucasians with two SNPs (rs213950-rs1042077) identified as related genotype in exon region. Conclusions Chinese population showed significantly different genetic spectrum pattern in CFTR gene compared with Caucasian population, and thus a Chinese-specific CF screening panel is needed. |
| first_indexed | 2024-04-13T17:24:29Z |
| format | Article |
| id | doaj.art-ba420644441a4a719369557330036492 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-13T17:24:29Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-ba420644441a4a7193695573300364922022-12-22T02:37:51ZengBMCOrphanet Journal of Rare Diseases1750-11722022-03-0117111110.1186/s13023-022-02279-9Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to CaucasiansQi Ni0Xiang Chen1Ping Zhang2Lin Yang3Yulan Lu4Feifan Xiao5Bingbing Wu6Huijun Wang7Wenhao Zhou8Xinran Dong9Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, National Children’s Medical CenterCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical CenterCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical CenterDepartment of Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical CenterCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical CenterCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical CenterCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical CenterChildren’s Hospital and Institutes of Biomedical Sciences, Fudan University, National Children’s Medical CenterChildren’s Hospital and Institutes of Biomedical Sciences, Fudan University, National Children’s Medical CenterAbstract Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians. Materials and methods We reviewed 30,951 exome-sequencing samples, including 20,909 pediatric patient samples and 10,042 parent samples, from Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System (CCGT). After the in-lab filtration process, 477 candidate variants of CFTR gene were left and 53 variants were manually curated as pathogenic/likely-pathogenic (P/LP). These P/LP variants were adopted to estimate CF prevalence in three methods: the carrier frequency method, the permutation-combinations method and the Bayesian framework method. Allele frequencies of the 477 CFTR variants were compared with non-Finland European (NFE) and East Asian (EAS) from gnomAD database. To investigate the haplotype structure difference of CFTR, another 2067 whole-genome-sequencing samples from CCGT and 195 NFE from 1000 genome project were analyzed by Shapeit4 software. Result With the 53 manually curated P/LP variants in CFTR gene, we excluded individuals identified or suspected with CF and their parents in our cohorts and estimated the Chinese CF prevalence is approximately 1/128,434. Only 21 (39.6%) of the 53 variants were included in Caucasian specific CF screening panels, resulting in significantly under-estimation of CF prevalence in our children cohort (1/143,171 vs. 1/1,387,395, P = 5e−24) and parent’s cohort (1/110,127 vs. 1/872,437, P = 7e−10). The allele frequencies of six pathogenic variants (G970D, D979A, M469V, G622D, L88X, 1898+5G->T) were significantly higher in our cohorts compared with gnomAD-NFE population (all P-value < 0.1). Haplotype analysis showed more haplotype diversity in Chinese compared to Caucasians. In addition, G970D and F508del were founder mutation of Chinese and Caucasians with two SNPs (rs213950-rs1042077) identified as related genotype in exon region. Conclusions Chinese population showed significantly different genetic spectrum pattern in CFTR gene compared with Caucasian population, and thus a Chinese-specific CF screening panel is needed.https://doi.org/10.1186/s13023-022-02279-9Cystic fibrosisScreening panelPrevalence estimationAllele frequency comparisonHaplotype construction and comparison |
| spellingShingle | Qi Ni Xiang Chen Ping Zhang Lin Yang Yulan Lu Feifan Xiao Bingbing Wu Huijun Wang Wenhao Zhou Xinran Dong Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians Orphanet Journal of Rare Diseases Cystic fibrosis Screening panel Prevalence estimation Allele frequency comparison Haplotype construction and comparison |
| title | Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians |
| title_full | Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians |
| title_fullStr | Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians |
| title_full_unstemmed | Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians |
| title_short | Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians |
| title_sort | systematic estimation of cystic fibrosis prevalence in chinese and genetic spectrum comparison to caucasians |
| topic | Cystic fibrosis Screening panel Prevalence estimation Allele frequency comparison Haplotype construction and comparison |
| url | https://doi.org/10.1186/s13023-022-02279-9 |
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