Genome-wide copy number variation study in anorectal malformations
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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摘要Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder. © The Author 2012. Published by Oxford University Press. All rights reserved.
著者Wong E.H.M., Cui L., Ng C.-L., Tang C.S.M., Liu X.-L., So M.-T., Yip B.H.-K., Cheng G., Zhang R., Tang W.-K., Yang W., Lau Y.-L., Baum L., Kwan P., Sun L.-D., Zuo X.-B., Ren Y.-Q., Yin X.-Y., Miao X.-P., Liu J., Lui V.C.-H., Ngan E.S.-W., Yuan Z.-W., Zhang S.-W., Xia J., Wang H., Sun X.-B., Wang R., Chang T., Chan I.H.-Y., Chung P.H.-Y., Zhang X.-J., Wong K.K.-Y., Cherny S.S., Sham P.-C., Tam P.K.-H., Garcia-Barcelo M.-M.
期刊名稱Human Molecular Genetics
出版年份2013
月份2
日期1
卷號22
期次3
出版社Oxford University Press
出版地United Kingdom
頁次621 - 631
國際標準期刊號0964-6906
電子國際標準期刊號1460-2083
語言英式英語

上次更新時間 2020-26-11 於 02:31