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Twin Res Hum Genet. 2018 Oct;21(5):361-368. doi: 10.1017/thg.2018.41. Epub 2018 Aug 1.

Four-Generation Pedigree of Monozygotic Female Twins Reveals Genetic Factors in Twinning Process by Whole-Genome Sequencing.

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School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Jinan,Shandong,China.
Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing,China.
Department of Hepatobiliary Surgery,Shandong Cancer Hospital Affiliated to Shandong University,Shandong Academy of Medical Sciences,Jinan,Shandong,China.
Department of Imaging,Shandong Cancer Hospital Affiliated to Shandong University,Shandong Academy of Medical Sciences,Jinan,Shandong,China.


Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5'UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.


genetic factors; monozygotic twins; twinning mechanism; whole-genome sequencing


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