Abstract
Background: Structural chromosome abnormality (SCA) is an important cause of human diseases, including recurrent pregnancy loss (RPL). DNA double-strand breaks (DSBs) repair-related genes play critical roles in SCA. The present study aims to investigate the potential contribution of DSBs repair-related gene polymorphisms to SCA. Methods: Fifty-four affected RPL individuals with SCA, 88 affected RPL individuals without SCA, and 84 controls were analyzed. Targeted whole-exome sequencing (WES) was used for screening single nucleotide polymorphisms in six DSBs repair-related genes (EP300, XRCC6, LIG4, XRCC4, PRKDC, and DCLRE1C), and validation was performed by Sanger sequencing. Finally, we detected the frequency of radiation-induced chromosome translocations in no SCA samples with significant polymorphisms by fluorescence in situ hybridization (FISH). Results: A total of 35 polymorphisms have been identified and confirmed. Frequencies of EP300 rs20551, XRCC6 rs132788, and LIG4 rs1805388 were significantly different between SCA RPL and no SCA RPL (p = 0.030, 0.031, and 0.040 respectively). Frequencies of those three gene polymorphisms between SCA RPL and controls also were significantly different (p = 0.017, 0.028, and 0.029 respectively). Moreover, the frequency of the G allele at rs20551 locus, the T allele at rs132788 locus and the A allele at rs1805388 locus was significantly higher in SCA RPL than no SCA RPL (OR = 3.227, p = 0.005; OR = 1.978, p = 0.008 and OR = 1.769, p = 0.036 respectively) and controls (OR = 7.130, p = 0.000; OR = 2.157, p = 0.004; OR = 2.397, p = 0.003 respectively). Additionally, the frequency of radiation-induced translocation in no SCA samples with rs20551, rs132788 or rs1805388 was significantly higher compared with the wild type samples (p = 0.015, 0.012, and 0.007 respectively). Conclusion: Our results suggest that rs20551, rs132788, and rs1805388 might be associated with the risk of SCA. Larger scales of genetic variations studies and functional experiments are necessary to further confirm these findings.
Highlights
Structural chromosome abnormality (SCA) is an important cause of human diseases including recurrent pregnancy loss (RPL) (Rai and Regan, 2006)
We investigated the potential contribution of EP300, XRCC6, LIG4, XRCC4, PRKDC, and DCLRE1C gene polymorphisms to structural chromosome abnormalities (SCA) based on recurrent pregnancy loss
A total of 35 polymorphisms had been identified in our samples (Table 2), nine within EP300, two within XRCC6, four within LIG4, three within XRCC4, ten within PRKDC and seven within DCLRE1C by whole-exome sequencing (WES)
Summary
Structural chromosome abnormality (SCA) is an important cause of human diseases including recurrent pregnancy loss (RPL) (Rai and Regan, 2006). Types of SCA include translocation, inversion, deletion, Tandem duplication, ring chromosome, etc. The most common SCA in women with RPL is translocation (usually 60% reciprocal and 40% Robertsonian approximately), and the segregation during meiosis can result in gametes with duplication or deficiency of chromosome segments (Prosée et al, 2020). The formation of SCA is considered a multistep process, and the initial event is the concomitant occurrence of DNA double-strand breaks (DSB) in multiple chromosomal locations (Nambiar and Raghavan, 2011). Structural chromosome abnormality (SCA) is an important cause of human diseases, including recurrent pregnancy loss (RPL). DNA double-strand breaks (DSBs) repair-related genes play critical roles in SCA. The present study aims to investigate the potential contribution of DSBs repair-related gene polymorphisms to SCA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
