Correlation Research About The Early Spontaneous Abortion Disease-causing Gene

Objective Discuss the correlation of the copy number variants of early spontaneous abortion chromosome and the loss of heterozygosity with the early abortion on genetic level.And analyse the correlation of the embryonic genome with the parent syndrome of TCM.Methods Using Affymetrix Cytoscan 750K to do the chromosome microarray anlysis(CMA)on early spontaneous abortuses from 30 early abortion patient.After eliminating some normal factors of abortion,like.chromosome abnormalities,parent uterine malformation and microbial infection,then test the copy number variants of the genome.And anlyse the result from the chip using certain software.And then we compare the resulting copy number variants and the loss of heterozygosity with Database of Genomic Variants,eliminate some normal polymorphism CNV,and also compare the data from DECIPHER、ISCA、OMIM and previously published paper,to analyse the pathogenicity of of the copy number variants of chromosome and the loss of heterozygosity.For these 30 sample,we also analyse the parent syndrome of TCM,and divide them into 2 groups depends on the result from the gene chips,one have the abnormal chromosome and the other have the normal chromosome,and analyse the correlation of parent syndrome of TCM between these two groups.Results ①26 of the 30 samples were anlied successfully,Test the success rate of 86.7%.Detected abnormalities in 15 cases,including 6 cases of aneuploidy;6 case of CNVs and 2 cases of LOH.6 of normal chromosome karyotype samples were anlied as aneuploid by CMA,it means false negative rate of the G band karyotype analysis technology is 26.9%.②Among the 26 anlied successfully samples,there were 11 CNVs and 3 LOH.6 CNVs among them are pathogenic.Gene KANK1、SMARCA2、HDAC4、KIF1 A、PMP22 are seemed pathogenic.Compared the data from DECIPHER、ISC A、OMIM and previously published paper,we find two virulent fragment.Also in this experiment,some missing repeating segments are related to NFATc1、ERCC6、RPS4X gene which are related to the embryo damage which have been found in some animal experiments,so we suspect that these three genes are related to early abortion.③Abnormal chromosome group contains 8 samples of Kidney deficiency syndrome,3 sample of Heat in Blood System,2 samples of Qi weakness syndrome and 1 sample of syndrome of blood stasis.Normal chromosome group contains 7 sample of Kidney deficiency syndrome、2 samples of Heat in Blood System and 3 samples of Qi weakness syndrome.The difference of embryonic genome has no explicit correlation with、the parent syndrome of TCM.Conclusion ①The G band karyotype analysis technology has certain false negative rate,but it is cheap and has high performance cost ratio.So it is still the fisrt choice of clinical chromosome abnormality analysis.But for some patient who has normal abortuses karyotype but has recidivity abortion,can suggest them to do the chromosome microarray analysis.②The chromosome microarray analysis has high throughput,high resolution,high sensitivity,and high accuracy,which cover the shortage of the G band karyotype analysis,and can be a new method of abortuses analysis in the future.But it also has some disadvantages like can not recognise the reorder of balance and high cost.③This research find 6 pathogenic CNVs,Gene KANK1、SMARCA2、HDAC4、KIF1 A、PMP22 are seemed pathogenic.Also in this experiment,some missing repeating segments are related to NFATc1、ERCC6、RPS4X gene which are related to the embryo damage which have been found in some animal experiments.④The difference of embryonic genome has no explicit correlation with the parent syndrome of TCM、age、abortion times and gestational age.