Genetic Analysis Of A Myotonic Dystrophy Family In Tianjin

Objective:To study and determine the gene type of a family myotonic dystrophy. By screening the differential gene expression between myotonic muscular dystrophy family members and healthy genes, aimed at analyze the possible disease-related gene with DM.Methods:A follow-up survey by appointment in Tianjin was done to all the family members of a myotonic dystrophy patient, including the clinical features, biochemical and ECG electrocardiogram among others. The venous blood collected from all family members was used as the sample for the test of PCR (Polymerase Chain Reaction) and gene sequencing analysis, so that gene type detection of the family members can be achieved. Using the gene chip technology, a gene chip system and selecting 3 members who are propend, mild and asymptomatic patients, the differences of whole blood gene expression could be screened. With bioinformatics tools, the metabolic pathway could be analyzed to changes in differential gene. While the application of GO (gene ontology) functional group can help classify the function of differential genes.Results:(1) The first intron in ZNF9 contains a complex repeat motif (TG)n(TCTG)n(CCTG)n. Significant expansion of the (TG)n(TCTG)n(CCTG)n repeat was examined in myotonic dystrophy family.(2) Compared with the control group,529 genes were differentially expressed including 6 genes significantly differentially expressed on chromosome 7, 15,2,14,16,8.25 down-regulated clusters and 5 up-regulated clusters could be classified by Matlab analysis software combined with GO or gene ontology database. KEGG pathways analysis showed 3 down-regulated pathways and 1 up-regulated pathway.(3) There were 54 differential genes expressed on chromosome 2,62 differential genes expressed on chromosome 3,42 differential genes expressed on chromosome 4,57 up-regulated and 64 down-regulated differential genes expressed on chromosome 19,38 down-regulated differential genes expressed on chromosome 22.(4) The functional genic clusters involved:cellular process, metabolic process, biological regulation.Cone I us i ons:(1) The type of this Tianjin myotonic dystrophy family is DM2.(2) Gene chips revealed that 529 genes were differentially expressed, including six of which were significantly expressed, thus form the differences in gene expression spectra of the blood of myotonic dystrophy type 2 family members. Each gene's role in DM remains to be further explored and confirmed.(3) Three of these biological signal transductions involved with the differential genes were reduced significantly, while one rised significantly. Cluster analysis of differential gene functions shows that GO functional cluster mainly was related to the changes of cellular process, metabolic process and biological regulation.(4) Not only did differential gene abnormally expressed on the chromosome 3, but also abnormally expressed on chromosome 4, and chromosome 22.In short, the major genes that cause tonic muscular dystrophy type 2 is on the 3q21.3 region. It is the abnormally repeating of ZNF9 intron 1 in the (TG)n(TCTG)n(CCTG) short string of nucleotides that caused the expansion, at the same time accompanied by abnormally expression of No.3 chromosome and other variety of chromosomes. The role played by the abnormally expressed genes in pathogenesis of DM warrant further studies to elucidate.