Back to Search
Start Over
Preimplantation genetic testing for a family with usher syndrome through targeted sequencing and haplotype analysis
- Source :
- BMC Medical Genomics, Vol 12, Iss 1, Pp 1-8 (2019), BMC Medical Genomics
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
Abstract
- Background Preimplantation genetic testing for monogenic defects (PGT-M) has been available in clinical practice. This study aimed to validate the applicability of targeted capture sequencing in developing personalized PGT-M assay. Methods One couple at risk of transmitting Usher Syndrome to their offspring was recruited to this study. Customized capture probe targeted at USH2A gene and 350 kb flanking region were designed for PGT-M. Eleven blastocysts were biopsied and amplified by using multiple displacement amplification (MDA) and capture sequencing. A hidden Markov model (HMM) assisted haplotype analysis was performed to deduce embryo’s genotype by using single nucleotide polymorphisms (SNPs) identified in each sample. The embryo without paternal rare variant was implanted and validated by conventional prenatal or postnatal diagnostic means. Results Four embryos were diagnosed as free of father’s rare variant, two were transferred and one achieved a successful pregnancy. The fetal genotype was confirmed by Sanger sequencing of fetal genomic DNA obtained by amniocentesis. The PGT-M and prenatal diagnosis results were further confirmed by the molecular diagnosis of the baby’s genomic DNA sample. The auditory test showed that the hearing was normal. Conclusions Targeted capture sequencing is an effective and convenient strategy to develop customized PGT-M assay.
- Subjects :
- Adult
0301 basic medicine
Heterozygote
lcsh:Internal medicine
Genotype
lcsh:QH426-470
Usher syndrome
Prenatal diagnosis
Fertilization in Vitro
Biology
Polymorphism, Single Nucleotide
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Genetics
medicine
Humans
lcsh:RC31-1245
Preimplantation Diagnosis
Genetics (clinical)
Genetic testing
Chromosome Aberrations
Sanger sequencing
Extracellular Matrix Proteins
030219 obstetrics & reproductive medicine
Preimplantation genetic testing
medicine.diagnostic_test
Haplotype
Multiple displacement amplification
DNA
Sequence Analysis, DNA
Targeted capture sequencing
Amniotic Fluid
Embryo, Mammalian
Fetal Blood
medicine.disease
Markov Chains
Pedigree
lcsh:Genetics
030104 developmental biology
Haplotypes
Amniocentesis
symbols
Female
Usher Syndromes
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 17558794
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Medical Genomics
- Accession number :
- edsair.doi.dedup.....4d4132444b912e9fd734d1a161974b78