Pathogenic variants of BUB1 and BUBR1 genes are not prioritized in screening tests of couples with aborted aneuploid fetuses

Document Type : Short communication

Authors

1 Department of Molecular Genetics, Faculty of Basic Sciences and advanced Technologies in Biology, University of Science and Culture, ACECR, Tehran, Iran

2 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Abstract

Chromosome aberrations certainly aneuploidie are the cause of the majority of spontaneous abortions in humans. BUB1 (budding uninhibited by benzimidazole 1) and BUBR1 (BUB1 mitotic checkpoint serine/threonine kinase B) are two key proteins mediating spindle-checkpoint activation that play a role in the inhibition of the anaphase-promoting complex/ cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. This study aimed to evaluate the probable roles of BUB1 and BUBR1 pathogenic variants in abortion of the fetuses with aneuploidy. Fifty aborted fetuses with approved aneuploidy using array comparative genomic hybridization (aCGH) were included. BUB1 and BUBR1 genes were studied using the Sanger sequencing for the single nucleotide variant (SNV) detection, certainly rs121909055 and rs28989185 as the pathogenic target variants. The sequencing results were analyzed by finch TV software.Neither homozygous nor heterozygous variant of the targeted SNVs was observed in the samples. No other SNV was detectable in the analyzed parts of the BUB1 and BUBR1 genes in all samples. Since the allele frequencies of the variants of interest were zero in 50 studied samples, these SNVs would not be prioritized for screening in the parents with a history of miscarriage due to aneuploidy.

Keywords

References

  1. Kavalier F. Investigation of recurrent miscarriages. BMJ 2005;331:121-122.
  2. Jia CW, Wang L, Lan YL, Song R, Zhou LY, Yu L, Yang Y, Liang Y, Li Y, Ma YM, Wang SY. Aneuploidy in early miscarriage and its related factors. Chin Med J (Engl) 2015;128: 2772-2776.
  3. Kim T, Gartner A. Bub1 kinase in the regulation of mitosis. Anim Cells Syst (Seoul) 2021; 25:1-10.
  4. Lagirand-Cantaloube J, Ciabrini C, Charrasse S, Ferrieres A, Castro A, Anahory T, Lorca T. Loss of centromere cohesion in aneuploid human oocytes correlates with decreased kinetochore localization of the sac proteins Bub1 and Bubr1. Sci Rep 2017;7:44001.
  5. Lara-Gonzalez P, Pines J, Desai A. Spindle assembly checkpoint activation and silencing at kinetochores. Semin Cell Dev Biol 2021;117:86-98.
  6. Perera D, Tilston V, Hopwood JA, Barchi M, Boot-Handford RP, Taylor SS. Bub1 maintains centromeric cohesion by activation of the spindle checkpoint. Dev Cell 2007;13:566-579.
  7. Schmid M, Steinlein C, Tian Q, Hanlon Newell AE, Gessler M, Olson SB, Rosenwald A, Kneitz B, Fedorov LM. Mosaic variegated aneuploidy in mouse BubR1 deficient embryos and pregnancy loss in human. Chromosome Res 2014;22:375-392.
  8. National Center for Biotechnology Information [Available from: https://www.ncbi.nlm.nih.gov/ clinvar/variation/7083/?oq=rs121909055&m=NM_004336. (BUB1):c.1475C%3EA%20(p.Ser492Tyr)].
  9. Hanks S, Coleman K, Reid S, Plaja A, Firth H, FitzPatrick D, Kidd A, Mehes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 2004;36:1159-1161.
  10. National Center for Biotechnology Information [Available from: https://www.ncbi.nlm.nih.gov/ clinvar/variation/133772/?oq=rs34998711&m=NM_001211.6(BUB1B):c.3011A%3EG%20(p.Asn1004Ser)].
  11. Yang L, Tao T, Zhao X, Tao H, Su J, Shen Y, Tang Y, Qian F, Xiao J. Association between fetal chromosomal abnormalities and the frequency of spontaneous abortions. Exp Ther Med 2020;19:2505-2510.
  12. Shi Q, Hu M, Luo M, Liu Q, Jiang F, Zhang Y, Wang S, Yan C, Weng Y. Reduced expression of Mad2 and Bub1 proteins is associated with spontaneous miscarriages. Mol Hum Reprod 2011;17:14-21.
  13. Akhoundi F, Parvaneh N, Modjtaba E-B. In silico analysis of deleterious single nucleotide polymorphisms in human BUB1 mitotic checkpoint serine/threonine kinase B gene. Meta Gene 2016;9:142-150.
  14. Zhao J, Li H, Chen G, Du L, Xu P, Zhang X, Xie M, Cao T, Li H. Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation. Mol Cytogenet 2021;14:22.
  15. Mou J-T, Huang S-X, Yu L-L, Xu J, Deng Q-L, Xie Y-S, Deng K. Identification of genetic polymorphisms in unexplained recurrent spontaneous abortion based on whole exome sequencing. Ann Transl Med 2022;10:603.
  16. Biswas L, Tyc K, El Yakoubi W, Morgan K, Xing J, Schindler K. Meiosis interrupted: the genetics of female infertility via meiotic failure. Reproduction 2021;161:R13-R35.

Files

Share

How to cite

Statistics