Four-Generation Pedigree of Monozygotic Female Twins Reveals Genetic Factors in Twinning Process by Whole-Genome Sequencing. (1st August 2018)

• Record Type: Journal Article
• Authors: Liu, Shiqi; Hong, Yaqiang; Cui, Kai; Guan, Jinxia; Han, Lu; Chen, Wei; Xu, Zhe; Gong, Kenan; Ou, Yang; Zeng, Changqing; Li, Sheng; Zhang, Dake; Hu, Dawei
• Is Part Of: Twin research and human genetics. Volume 21:Number 5(2018)
• Page Start: 361
• Page End: 368
• Publication Date: 2018-08-01
• Subjects: genetic factors, -- monozygotic twins, -- twinning mechanism, -- whole-genome sequencing; Twins -- Periodicals; Multiple birth -- Periodicals; 618.25
• DOI: 10.1017/thg.2018.41
• Languages: English
• ISSNs: 1832-4274

Abstract

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.