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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.

Author information

1
School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Jinan,Shandong,China.
2
Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing,China.
3
Department of Hepatobiliary Surgery,Shandong Cancer Hospital Affiliated to Shandong University,Shandong Academy of Medical Sciences,Jinan,Shandong,China.
4
Department of Imaging,Shandong Cancer Hospital Affiliated to Shandong University,Shandong Academy of Medical Sciences,Jinan,Shandong,China.

Abstract

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.

KEYWORDS:

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

PMID:
30064533
DOI:
10.1017/thg.2018.41

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