Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro.
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,...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2014
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| _version_ | 1797064851064881152 |
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| author | Natesan, SA Bladon, A Coskun, S Qubbaj, W Prates, R Munne, S Coonen, E Dreesen, J Stevens, S Paulussen, A Stock-Myer, SE Wilton, L Jaroudi, S Wells, D Brown, A Handyside, A |
| author_facet | Natesan, SA Bladon, A Coskun, S Qubbaj, W Prates, R Munne, S Coonen, E Dreesen, J Stevens, S Paulussen, A Stock-Myer, SE Wilton, L Jaroudi, S Wells, D Brown, A Handyside, A |
| author_sort | Natesan, SA |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:20:17Z |
| format | Journal article |
| id | oxford-uuid:4139a879-08b4-4537-9ae7-4527b3d76daf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:20:17Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:4139a879-08b4-4537-9ae7-4527b3d76daf2022-03-26T14:42:19ZGenome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4139a879-08b4-4537-9ae7-4527b3d76dafEnglishSymplectic Elements at Oxford2014Natesan, SABladon, ACoskun, SQubbaj, WPrates, RMunne, SCoonen, EDreesen, JStevens, SPaulussen, AStock-Myer, SEWilton, LJaroudi, SWells, DBrown, AHandyside, APURPOSE: 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. |
| spellingShingle | Natesan, SA Bladon, A Coskun, S Qubbaj, W Prates, R Munne, S Coonen, E Dreesen, J Stevens, S Paulussen, A Stock-Myer, SE Wilton, L Jaroudi, S Wells, D Brown, A Handyside, A Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. |
| title | Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. |
| title_full | Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. |
| title_fullStr | Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. |
| title_full_unstemmed | Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. |
| title_short | Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. |
| title_sort | genome wide karyomapping accurately identifies the inheritance of single gene defects in human preimplantation embryos in vitro |
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