Rare Diseases Symptoms Automatic Extraction

[Combination of multiple displacement amplification with short tandem repeat polymorphismin preimplantation genetic diagnosis].

[alpha-thalassemia]

To explore the application of multiple displacement amplification (MDA) combined with short tandem repeats (STRs) in preimplantation genetic diagnosis (PGD).MDA was applied to amplify the whole genome of a single cell and to retrieve and assemble the highly heterogeneous STR loci among human population. Haplotype analytic system was established with aiming at diagnosis of the single gene diseases by selecting the STR loci located within the pathogenic genes or on both bounding sides of the pathogenic genes. At the same time, allele specific amplification, PCR-reverse dot-blotting hybridization methods and gene sequencing methods were employed for direct detection of the pathogenic genes. The STR loci located at related chromosomes were selected to carry out allele number analysis on the basis of chromosome number and structural abnormality.In the study, 12 PGD systems were set up including 6 different monogenic diseases (spinal muscular atrophy, Duchenne muscular dystrophy, X-linked chronic granulomatous disease, osteopetrosis, achondroplasia, X-linked severe combined immunodeficiency), Robertsonian translocations, α-thalassemia combined with Robertsonian translocation, α- and β-double thalassemia, β-thalassemia with HLA typing and DMD with HLA typing. Then 44 PGD cycles were performed for 35 couples with different kinds of inherited diseases, which resulted in 20 healthy liveborns (12 singletons and 4 twins) and 5 ongoing pregnancies. The clinical pregnancy rate was 47.7% (21/44) per PGD cycle. The overall diagnostic rate was 94.6% (367/388). The MDA failed in 3.6% (14/388) single blastomeres. The amplification rate of the subsequent PCR was 97.1% and the average allele drop out (ADO) rate was 12.6% (range: 0-47.5%).The application of MDA combined with STRs provided a generic PGD approach for different genetic disorders, especially for simultaneous diagnosis of two or more hereditary statuses. The method could greatly shorten the time of developing PGD system of new diseases, which broadens the indications of PGD.

Diseases presenting "specific amplification" symptom

  • achondroplasia
  • alpha-thalassemia
  • cholangiocarcinoma

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