Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect
Wilson’s disease (WD) is an autosomal recessive disorder caused by <i>ATP7B</i> pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify...
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MDPI AG
2021-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/3/336 |
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| author | Guo-Min Yang Rou-Min Wang Nan Xia Zi-Wei Zheng Yi Dong Zhi-Ying Wu |
| author_facet | Guo-Min Yang Rou-Min Wang Nan Xia Zi-Wei Zheng Yi Dong Zhi-Ying Wu |
| author_sort | Guo-Min Yang |
| collection | DOAJ |
| description | Wilson’s disease (WD) is an autosomal recessive disorder caused by <i>ATP7B</i> pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the <i>ATP7B</i> gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (<i>p </i>< 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective. |
| first_indexed | 2024-03-09T00:32:47Z |
| format | Article |
| id | doaj.art-b56fb7261d8640d9a35368a68a09ed8b |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T00:32:47Z |
| publishDate | 2021-02-01 |
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| series | Genes |
| spelling | doaj.art-b56fb7261d8640d9a35368a68a09ed8b2023-12-11T18:23:29ZengMDPI AGGenes2073-44252021-02-0112333610.3390/genes12030336Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder EffectGuo-Min Yang0Rou-Min Wang1Nan Xia2Zi-Wei Zheng3Yi Dong4Zhi-Ying Wu5Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, ChinaWilson’s disease (WD) is an autosomal recessive disorder caused by <i>ATP7B</i> pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the <i>ATP7B</i> gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (<i>p </i>< 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective.https://www.mdpi.com/2073-4425/12/3/336Wilson’s disease<i>ATP7B</i>haplotype analysisfounder effectChinese |
| spellingShingle | Guo-Min Yang Rou-Min Wang Nan Xia Zi-Wei Zheng Yi Dong Zhi-Ying Wu Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect Genes Wilson’s disease <i>ATP7B</i> haplotype analysis founder effect Chinese |
| title | Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect |
| title_full | Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect |
| title_fullStr | Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect |
| title_full_unstemmed | Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect |
| title_short | Prevalent Pathogenic Variants of <em>ATP7B </em>in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect |
| title_sort | prevalent pathogenic variants of em atp7b em in chinese patients with wilson s disease geographical distribution and founder effect |
| topic | Wilson’s disease <i>ATP7B</i> haplotype analysis founder effect Chinese |
| url | https://www.mdpi.com/2073-4425/12/3/336 |
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