Mitotic arrest deficient 1 like 1 (MAD1L1) gene variations in products of conception with aneuploidy

Background: More than 57% of spontaneous abortions are due to chromosomal abnormalities, certainly aneuploidies. Although aneuploidy is associated with advanced maternal age it is frequent in young women. Spindle assembly checkpoint (SAC) complex has a critical role in correct chromosome segregation during cell division. Several genes are involved in SAC, one of them is MAD1L1.Objective: We investigated pathogenic single nucleotide variations (SNVs) of MAD1L1, rs121908982 and rs121908981 and their upstream and downstream SNVs to investigate their association with aneuploidy in products of conception (POC).Materials and Methods: POC of mothers aged <36 were analyzed using quantitative fluorescence polymerase chain reaction (QF-PCR) and/or array comparative genomic hybridization (aCGH). Those with aneuploidy were enrolled in genotyping. Areas of interest of MAD1L1 were genotyped using PCR followed by Sanger sequencing. Comparison of the observed SNVs frequencies with the highest population minor allele frequency (MAF) was performed using Chi Square.Results: According to QF-PCR and aCGH results, 40 aneuploid samples enrolled in genotyping. We didn’t observe those pathogenic SNVs but observed rs10260386, rs1481591257, rs10257349, rs372373978, rs752408355, rs1639921, rs376061507, rs62442486, rs74431414 SNVs with following allele frequencies and p-values of comparison with the highest population MAF: A:0.7/G:0.3 (p<0.0001), G:0.9875/A:0.0125 (p=0.8222), T:0.4/C:0.6 (p=0.2816), G:0.9875/0.0125 (p=0.8222), A:0.9875/G: 0.0125 (p=0.1775), T:0.875/C:0.125 (p<0.0001), T:0.6806/C:0.3194 (p<0.0001), A:0.68/G:0.32 (p<0.0001) and G:0.9583/T:0.0417 (p=0.9425), respectively.Conclusion: Frequencies of rs10260386, rs1639921, rs376061507 and rs62442486 SNVs were obviously higher than the highest population MAF. These SNVs seem to be associated with aneuploidy in POC.

کلیدواژه ها:

Abortion ، Aneuploidy ، MAD1L1 ، Single nucleotide variation (SNV)