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Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq

Current approaches to detect and characterize mosaic chromosomal aneuploidy are limited by sensitivity, efficiency, cost, or the need to culture cells. We describe the mosaic aneuploidy detection by massively parallel sequencing (MAD-seq) capture assay and the MADSEQ analytical approach that allow l...

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Autores principales: Kong, Yu, Berko, Esther R., Marcketta, Anthony, Maqbool, Shahina B., Simões-Pires, Claudia A., Kronn, David F., Ye, Kenny Q., Suzuki, Masako, Auton, Adam, Greally, John M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028128/
https://www.ncbi.nlm.nih.gov/pubmed/29773658
http://dx.doi.org/10.1101/gr.226282.117
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author Kong, Yu
Berko, Esther R.
Marcketta, Anthony
Maqbool, Shahina B.
Simões-Pires, Claudia A.
Kronn, David F.
Ye, Kenny Q.
Suzuki, Masako
Auton, Adam
Greally, John M.
author_facet Kong, Yu
Berko, Esther R.
Marcketta, Anthony
Maqbool, Shahina B.
Simões-Pires, Claudia A.
Kronn, David F.
Ye, Kenny Q.
Suzuki, Masako
Auton, Adam
Greally, John M.
author_sort Kong, Yu
collection PubMed
description Current approaches to detect and characterize mosaic chromosomal aneuploidy are limited by sensitivity, efficiency, cost, or the need to culture cells. We describe the mosaic aneuploidy detection by massively parallel sequencing (MAD-seq) capture assay and the MADSEQ analytical approach that allow low (<10%) levels of mosaicism for chromosomal aneuploidy or regional loss of heterozygosity to be detected, assigned to a meiotic or mitotic origin, and quantified as a proportion of the cells in the sample. We show results from a multi-ethnic MAD-seq (meMAD-seq) capture design that works equally well in populations of diverse racial and ethnic origins and how the MADSEQ analytical approach can be applied to exome or whole-genome sequencing data, revealing previously unrecognized aneuploidy or copy number neutral loss of heterozygosity in samples studied by the 1000 Genomes Project, cell lines from public repositories, and one of the Illumina Platinum Genomes samples. We have made the meMAD-seq capture design and MADSEQ analytical software open for unrestricted use, with the goal that they can be applied in clinical samples to allow new insights into the unrecognized prevalence of mosaic chromosomal aneuploidy in humans and its phenotypic associations.
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spelling pubmed-60281282019-01-01 Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq Kong, Yu Berko, Esther R. Marcketta, Anthony Maqbool, Shahina B. Simões-Pires, Claudia A. Kronn, David F. Ye, Kenny Q. Suzuki, Masako Auton, Adam Greally, John M. Genome Res Method Current approaches to detect and characterize mosaic chromosomal aneuploidy are limited by sensitivity, efficiency, cost, or the need to culture cells. We describe the mosaic aneuploidy detection by massively parallel sequencing (MAD-seq) capture assay and the MADSEQ analytical approach that allow low (<10%) levels of mosaicism for chromosomal aneuploidy or regional loss of heterozygosity to be detected, assigned to a meiotic or mitotic origin, and quantified as a proportion of the cells in the sample. We show results from a multi-ethnic MAD-seq (meMAD-seq) capture design that works equally well in populations of diverse racial and ethnic origins and how the MADSEQ analytical approach can be applied to exome or whole-genome sequencing data, revealing previously unrecognized aneuploidy or copy number neutral loss of heterozygosity in samples studied by the 1000 Genomes Project, cell lines from public repositories, and one of the Illumina Platinum Genomes samples. We have made the meMAD-seq capture design and MADSEQ analytical software open for unrestricted use, with the goal that they can be applied in clinical samples to allow new insights into the unrecognized prevalence of mosaic chromosomal aneuploidy in humans and its phenotypic associations. Cold Spring Harbor Laboratory Press 2018-07 /pmc/articles/PMC6028128/ /pubmed/29773658 http://dx.doi.org/10.1101/gr.226282.117 Text en © 2018 Kong et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Method
Kong, Yu
Berko, Esther R.
Marcketta, Anthony
Maqbool, Shahina B.
Simões-Pires, Claudia A.
Kronn, David F.
Ye, Kenny Q.
Suzuki, Masako
Auton, Adam
Greally, John M.
Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq
title Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq
title_full Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq
title_fullStr Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq
title_full_unstemmed Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq
title_short Detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using MAD-seq
title_sort detecting, quantifying, and discriminating the mechanism of mosaic chromosomal aneuploidies using mad-seq
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028128/
https://www.ncbi.nlm.nih.gov/pubmed/29773658
http://dx.doi.org/10.1101/gr.226282.117
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