Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro.
Genet Med
; 16(11): 838-45, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-24810687
ABSTRACT
PURPOSE:
Our aim was to compare the accuracy of family- or disease-specific targeted haplotyping and direct mutation-detection strategies with the accuracy of genome-wide mapping of the parental origin of each chromosome, or karyomapping, by single-nucleotide polymorphism genotyping of the parents, a close relative of known disease status, and the embryo cell(s) used for preimplantation genetic diagnosis of single-gene defects in a single cell or small numbers of cells biopsied from human embryos following in vitro fertilization.METHODS:
Genomic DNA and whole-genome amplification products from embryo samples, which were previously diagnosed by targeted haplotyping, were genotyped for single-nucleotide polymorphisms genome-wide detection and retrospectively analyzed blind by karyomapping.RESULTS:
Single-nucleotide polymorphism genotyping and karyomapping were successful in 213/218 (97.7%) samples from 44 preimplantation genetic diagnosis cycles for 25 single-gene defects with various modes of inheritance distributed widely across the genome. Karyomapping was concordant with targeted haplotyping in 208 (97.7%) samples, and the five nonconcordant samples were all in consanguineous regions with limited or inconsistent haplotyping results.CONCLUSION:
Genome-wide karyomapping is highly accurate and facilitates analysis of the inheritance of almost any single-gene defect, or any combination of loci, at the single-cell level, greatly expanding the range of conditions for which preimplantation genetic diagnosis can be offered clinically without the need for customized test development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mapeamento Cromossômico
/
Diagnóstico Pré-Implantação
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Técnicas de Genotipagem
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Cariotipagem
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
Limite:
Female
/
Humans
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Male
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido