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Whole-Exome Sequencing Identifies Mutation Signatures of Collagen-Containing Extracellular Matrix Genes in Polymelia

42 Pages Posted: 27 Jul 2020 Publication Status: Review Complete

See all articles by Tao Luo

Tao Luo

Fudan University - Shanghai Public Health Clinical Center

Zhanghan Chen

Fudan University - Department of General Surgery

Bo Yan

Fudan University - Shanghai Public Health Clinical Center

Zehuan Li

Fudan University - Department of General Surgery

Tianyi Qiu

Fudan University - Shanghai Public Health Clinical Center

Qiu Chen

Fudan University - Shanghai Public Health Clinical Center

Christopher Corpe

King’s College London - Diabetes and Nutritional Sciences

Song-Mei Liu

Wuhan University - Department of Laboratory Medicine

Juan Bao

Fudan University - Shanghai Public Health Clinical Center

Baoxue Sha

Fudan University - Shanghai Public Health Clinical Center

Hiroshi Katayama

Okayama University - Department of Molecular Oncology

Xiaoyan Zhang

Fudan University - Shanghai Public Health Clinical Center

Jianqing Xu

Fudan University - Shanghai Public Health Clinical Center

Tongyu Zhu

Fudan University - Shanghai Public Health Clinical Center

Jin Wang

Fudan University - Shanghai Public Health Clinical Center

More...

Abstract

Polymelia is a rare congenital disease in humans characterized by extra limbs and a poorly understood etiology. To understand the mechanisms responsible for polymelia, DNA was isolated from two polymelia children with congenital malformations and their healthy parents for whole-exome sequencing. Using three hypothetical inheritance patterns and Ingenuity Pathway Analysis (IPA) the disease network analysis identified a network of Cancer, Connective Tissue Disorders, Organismal Injury and Abnormalities which included eleven mutated genes that might play roles in the proband multi-malformations. Variants in three collagen-associated genes, including rs146977141 c.5168 A > G and rs372335521 c.5207 C > T in COL27A1, c.1786_1794del and c.2106_2114del in COL18A1 and rs754836509 c.3940 C > T in COL4A5, were further validated. A significant defect of notochord was observedin both COL18A1 and COL4A5 morphants in zebrafish. Our results identified variants in collagen-containing extracellular matrix genes might be critical in the development of polymelia.

Keywords: Polymelia, Whole-Exome Sequencing, Disease Network Analysis, Collagen-associated genes

Suggested Citation

Luo, Tao and Chen, Zhanghan and Yan, Bo and Li, Zehuan and Qiu, Tianyi and Chen, Qiu and Corpe, Christopher and Liu, Song-Mei and Bao, Juan and Sha, Baoxue and Katayama, Hiroshi and Zhang, Xiaoyan and Xu, Jianqing and Zhu, Tongyu and Wang, Jin, Whole-Exome Sequencing Identifies Mutation Signatures of Collagen-Containing Extracellular Matrix Genes in Polymelia. Available at SSRN: https://ssrn.com/abstract=3640831 or http://dx.doi.org/10.2139/ssrn.3640831
This version of the paper has not been formally peer reviewed.

Tao Luo

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Zhanghan Chen

Fudan University - Department of General Surgery

Shanghai, 200032
China

Bo Yan

Fudan University - Shanghai Public Health Clinical Center ( email )

Shanghai
China

Zehuan Li

Fudan University - Department of General Surgery

Shanghai, 200032
China

Tianyi Qiu

Fudan University - Shanghai Public Health Clinical Center ( email )

Shanghai
China

Qiu Chen

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Christopher Corpe

King’s College London - Diabetes and Nutritional Sciences

United Kingdom

Song-Mei Liu

Wuhan University - Department of Laboratory Medicine ( email )

Wuhan, 430071
China

Juan Bao

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Baoxue Sha

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Hiroshi Katayama

Okayama University - Department of Molecular Oncology ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Xiaoyan Zhang

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Jianqing Xu

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Tongyu Zhu

Fudan University - Shanghai Public Health Clinical Center ( email )

Shanghai
China

Jin Wang (Contact Author)

Fudan University - Shanghai Public Health Clinical Center ( email )

Shanghai
China

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