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Application of mosaicism ratio to multifetal gestations

Mosaicism ratio, or MR, is a laboratory metric that can be calculated using massively parallel sequencing data from cell-free DNA (cfDNA) screening. MR compares the amount of cfDNA present from a particular chromosome or chromosomal region to the overall fetal fraction of the specimen. In singleton...

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Autores principales: Rafalko, Jill, Caldwell, Samantha, Soster, Erica, Almasri, Eyad, McLennan, Graham, Liu, Tong, Weinblatt, Vivian, Cacheris, Philip, McCullough, Ron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954340/
https://www.ncbi.nlm.nih.gov/pubmed/33711042
http://dx.doi.org/10.1371/journal.pone.0248467
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author Rafalko, Jill
Caldwell, Samantha
Soster, Erica
Almasri, Eyad
McLennan, Graham
Liu, Tong
Weinblatt, Vivian
Cacheris, Philip
McCullough, Ron
author_facet Rafalko, Jill
Caldwell, Samantha
Soster, Erica
Almasri, Eyad
McLennan, Graham
Liu, Tong
Weinblatt, Vivian
Cacheris, Philip
McCullough, Ron
author_sort Rafalko, Jill
collection PubMed
description Mosaicism ratio, or MR, is a laboratory metric that can be calculated using massively parallel sequencing data from cell-free DNA (cfDNA) screening. MR compares the amount of cfDNA present from a particular chromosome or chromosomal region to the overall fetal fraction of the specimen. In singleton gestations, MR may be used to refine the positive predictive value of an abnormal cfDNA screening result by identifying cases that could be impacted by various biological factors, such as placental mosaicism or prior co-twin demise. The current study was designed to examine the behavior of mosaicism ratio (MR) in multifetal gestations. Multifetal cfDNA specimens with positive results for trisomies 21, 18, or 13 and confirmed diagnostic outcomes were compiled to examine MR of the aneuploid chromosome based on the number of affected fetuses/placentas. A second multifetal cohort was assembled to analyze the MR of the Y chromosome in cases with at least one male fetus. For aneuploid cases, the average MR of affected singletons (used as a biological proxy for two affected twins) was significantly higher than the average MR for twins in which one fetus was affected. The average MR of the aneuploid chromosome for one affected twin was 52%, 42%, and 48% of that of singleton gestations for trisomy 21, 18, and 13 cases, respectively. MR cutoffs of 0.7 for trisomy 21, and 0.5 for trisomies 18 and 13 may help predict whether one versus both twins are affected with aneuploidy when clinical concern arises. For male cases, the Y MR of XX/XY gestations was 48% of the Y MR for XY/XY gestations. Using a Y MR cutoff of 0.8 allowed determination of XX/XY versus XY/XY gestations with 92.3–94.9% accuracy. Based on the data presented, MR may have utility in the analysis and interpretation of cfDNA data from multifetal gestations.
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spelling pubmed-79543402021-03-22 Application of mosaicism ratio to multifetal gestations Rafalko, Jill Caldwell, Samantha Soster, Erica Almasri, Eyad McLennan, Graham Liu, Tong Weinblatt, Vivian Cacheris, Philip McCullough, Ron PLoS One Research Article Mosaicism ratio, or MR, is a laboratory metric that can be calculated using massively parallel sequencing data from cell-free DNA (cfDNA) screening. MR compares the amount of cfDNA present from a particular chromosome or chromosomal region to the overall fetal fraction of the specimen. In singleton gestations, MR may be used to refine the positive predictive value of an abnormal cfDNA screening result by identifying cases that could be impacted by various biological factors, such as placental mosaicism or prior co-twin demise. The current study was designed to examine the behavior of mosaicism ratio (MR) in multifetal gestations. Multifetal cfDNA specimens with positive results for trisomies 21, 18, or 13 and confirmed diagnostic outcomes were compiled to examine MR of the aneuploid chromosome based on the number of affected fetuses/placentas. A second multifetal cohort was assembled to analyze the MR of the Y chromosome in cases with at least one male fetus. For aneuploid cases, the average MR of affected singletons (used as a biological proxy for two affected twins) was significantly higher than the average MR for twins in which one fetus was affected. The average MR of the aneuploid chromosome for one affected twin was 52%, 42%, and 48% of that of singleton gestations for trisomy 21, 18, and 13 cases, respectively. MR cutoffs of 0.7 for trisomy 21, and 0.5 for trisomies 18 and 13 may help predict whether one versus both twins are affected with aneuploidy when clinical concern arises. For male cases, the Y MR of XX/XY gestations was 48% of the Y MR for XY/XY gestations. Using a Y MR cutoff of 0.8 allowed determination of XX/XY versus XY/XY gestations with 92.3–94.9% accuracy. Based on the data presented, MR may have utility in the analysis and interpretation of cfDNA data from multifetal gestations. Public Library of Science 2021-03-12 /pmc/articles/PMC7954340/ /pubmed/33711042 http://dx.doi.org/10.1371/journal.pone.0248467 Text en © 2021 Rafalko et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rafalko, Jill
Caldwell, Samantha
Soster, Erica
Almasri, Eyad
McLennan, Graham
Liu, Tong
Weinblatt, Vivian
Cacheris, Philip
McCullough, Ron
Application of mosaicism ratio to multifetal gestations
title Application of mosaicism ratio to multifetal gestations
title_full Application of mosaicism ratio to multifetal gestations
title_fullStr Application of mosaicism ratio to multifetal gestations
title_full_unstemmed Application of mosaicism ratio to multifetal gestations
title_short Application of mosaicism ratio to multifetal gestations
title_sort application of mosaicism ratio to multifetal gestations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954340/
https://www.ncbi.nlm.nih.gov/pubmed/33711042
http://dx.doi.org/10.1371/journal.pone.0248467
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