Department of Clinical Medicine, Affiliated Hospital of Kunming University of Science and Technology (The First People's Hospital of Yunnan Province), Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
Department of Breast Surgery, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
Mol Med Rep. 2018 Jun;17(6):8391-8396. doi: 10.3892/mmr.2018.8912. Epub 2018 Apr 20.
Systemic lupus erythematosus (SLE) is an autoimmune disease, and its genetic causes remain to be fully elucidated. Previous studies have identified several susceptibility genes for SLE, such as deoxyribonuclease 1‑like 3. In the present study, whole‑genome sequencing (30X coverage) was performed on the leukocytes of a monozygotic twin discordant for SLE to assess the potential association of de novo variants and copy number variations (CNVs) with the susceptibility to SLE. After analyzing the genomic data, 8 putative discordant exonic variants between the twins were selected. However, the 8 variants that were chosen for validation with Sanger sequencing exhibited no discrepancy in the leukocytes from the twins. Of note, CNV alterations in genes of SLE‑associated pathways were identified between the twins, which may be linked with the phenotype of the monozygotic twin discordant for SLE. The above results suggest that genomic sequences of leukocytes in the monozygotic twins may exhibit a rare difference, and that CNV changes may be associated with phenotype differences in the twin discordant for SLE.
系统性红斑狼疮 (SLE) 是一种自身免疫性疾病，其遗传原因仍未完全阐明。先前的研究已经确定了 SLE 的几个易感基因，如脱氧核糖核酸酶 1 样 3。在本研究中，对一对单卵双胞胎中 SLE 不一致的白细胞进行全基因组测序 (30X 覆盖)，以评估新生变异和拷贝数变异 (CNV) 与 SLE 易感性的潜在关联。在分析基因组数据后，选择了双胞胎之间 8 个可能的差异外显子变异。然而，选择用于 Sanger 测序验证的 8 个变体在双胞胎的白细胞中没有差异。值得注意的是，在 SLE 相关通路的基因中发现了双胞胎之间的 CNV 改变，这可能与 SLE 不一致的单卵双胞胎的表型有关。上述结果表明，同卵双胞胎白细胞的基因组序列可能存在罕见的差异，CNV 变化可能与 SLE 不一致的双胞胎表型差异有关。
