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Single-cell transcriptomics reveals diverse and complex gene expression alterations in human trisomy 18

Wang, J.; Chen, Z.; He, F.; Lee, T.; Cai, W.; Chen, W.; Zhang, L.; Miao, N.; Zeng, Z.; Hussain, G.; Sun, T.; Guo, Q.

2019-12-03 genetics
10.1101/863332 bioRxiv
Show abstract

Trisomy 18, commonly known as Edwards syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed amniotic fluid cells from two normal and three trisomy 18 samples using single-cell transcriptomics. We identified six cell groups, which function in major tissue development such as kidney, vasculature, and smooth muscle, and display significant alterations in gene expression detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11, 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.

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