Deep sequencing shows that accumulation of potentially pathogenic mtDNA mutations rather than mtDNA copy numbers may be
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GENETICS
Deep sequencing shows that accumulation of potentially pathogenic mtDNA mutations rather than mtDNA copy numbers may be associated with early embryonic loss Licheng Ji 1 & Tingting Liao 1 & Juan Yang 1 & Houming Su 1 & Jianyuan Song 2 & Kun Qian 1 Received: 16 March 2020 / Accepted: 2 July 2020 # The Author(s) 2020
Abstract Purpose To explore the relationship between mitochondrial DNA quantity and heteroplasmy and early embryonic loss. Methods A total of 150 villous samples from patients with spontaneous abortion (SA, n = 75) or induced abortion (IA, n = 75) were collected. qPCR and next-generation sequencing (NGS) were used to test mitochondrial DNA quantity and heteroplasmy. Missense mutations with a CADD score > 15 and heteroplasmy ≥ 70% were defined as potentially pathogenic mutations. Results With respect to mitochondrial DNA copy numbers, there was no significant difference between the SA and IA groups (median (IQR), 566 (397–791) vs. 614 (457–739); P = 0.768) or between the euploid and aneuploid groups (median (IQR), 516 (345–730) vs. 599 (423–839); P = 0.107). mtDNA copy numbers were not associated with spontaneous abortion using logistic regression analysis (P = 0.196, 95% CI 1.000–1.001). In addition, more patients harbored possibly pathogenic mtDNA mutations in their chorionic villi in the SA group (70.7%, 53/75) compared with the IA group (54.7%, 41/75; P < 0.05). However, there was no statistical difference between the euploid (80%, 24/30) and aneuploid groups (64.4%, 29/45; p = 0.147). Conclusion Early embryonic loss and the formation of aneuploidy were not related to mtDNA copy number. Patients with spontaneous abortion were more likely to have possibly pathogenic mutations in their mtDNA, and this may assist in purifying pathogenic mtDNA. However, whether the accumulation of these potentially morbific mtDNA mutations caused early embryonic loss requires further investigation. Keywords Spontaneous abortion . Mitochondria . mtDNA copy number . Heteroplasmy . Next-generation sequencing (NGS)
Introduction About 10–15% of clinically recognized pregnancies result in miscarriage, with aneuploidy as the principal cause [1]. Trisomies are the most frequently observed type of aneuploidy (61.2%), followed by triploidies (12.4%), monosomy X Licheng Ji and Tingting Liao joint as first author. * Tingting Liao [email protected] * Kun Qian [email protected] 1
Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan 430030, Hubei, China
2
The Fourth Affiliated Hospital, Zhejiang University School of Medicine, No.1 Shang Cheng Avenue, Yiwu, Zhejiang 322000, China
(10.5%), tetraploidies (9.2%), and structural chromosomal anomalies (4.7%) [2]. In human cells, however, there is another genome—the mitochondrial (mtDNA) genome. In contrast to only two copies of nuclear DNA, a single human cell hosts hundreds to thousands of copies of mtDNA; the mitochondrially encoded proteins are essential for mitochondrial oxidat
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