Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma

Prenatal diagnosis of monogenic diseases, such as cystic fibrosis and β-thalassemia, is currently offered as part of public health programs. However, current methods based on chorionic villus sampling and amniocentesis for obtaining fetal genetic material pose a risk to the fetus. Since the discover...

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Main Authors: Fiona M.F. Luna, Nancy B.Y. Tsui, K. C.Allen Chan, Tak Y. Leung, Tze K. Lau, Pimlak Charoenkwan, Katherine C.K. Chow, Wyatt Y.W. Lo, Chanane Wanapirak, Torpong Sanguansermsri, Charles R. Cantor, Rossa W.K. Chiu, Y. M.Dennis Lo
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/60754
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-607542018-09-10T03:49:27Z Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma Fiona M.F. Luna Nancy B.Y. Tsui K. C.Allen Chan Tak Y. Leung Tze K. Lau Pimlak Charoenkwan Katherine C.K. Chow Wyatt Y.W. Lo Chanane Wanapirak Torpong Sanguansermsri Charles R. Cantor Rossa W.K. Chiu Y. M.Dennis Lo Multidisciplinary Prenatal diagnosis of monogenic diseases, such as cystic fibrosis and β-thalassemia, is currently offered as part of public health programs. However, current methods based on chorionic villus sampling and amniocentesis for obtaining fetal genetic material pose a risk to the fetus. Since the discovery of cell-free fetal DNA in maternal plasma, the noninvasive prenatal assessment of paternally inherited traits or mutations has been achieved. Due to the presence of background maternal DNA, which interferes with the analysis of fetal DNA in maternal plasma, noninvasive prenatal diagnosis of maternally inherited mutations has not been possible. Here we describe a digital relative mutation dosage (RMD) approach that determines if the dosages of the mutant and wild-type alleles of a disease-causing gene are balanced or unbalanced in maternal plasma. When applied to the testing of women heterozygous for the CD41/42 (-CTTT) and hemoglobin E mutations on HBB, digital RMD allows the fetal genotype to be deduced. The diagnostic performance of digital RMD is dependent on interplay between the fractional fetal DNA concentration and number of DNA molecules in maternal plasma. To achieve fetal genotype diagnosis at lower volumes of maternal plasma, fetal DNA enrichment is desired. We thus developed a digital nucleic acid size selection (NASS) strategy that effectively enriches the fetal DNA without additional plasma sampling or experimental time. We show that digital NASS can work in concert with digital RMD to increase the proportion of cases with classifiable fetal genotypes and to bring noninvasive prenatal diagnosis of monogenic diseases closer to reality. © 2008 by The National Academy of Sciences of the USA. 2018-09-10T03:49:27Z 2018-09-10T03:49:27Z 2008-12-16 Journal 10916490 00278424 2-s2.0-58149401202 10.1073/pnas.0810373105 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=58149401202&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/60754
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Multidisciplinary
spellingShingle Multidisciplinary
Fiona M.F. Luna
Nancy B.Y. Tsui
K. C.Allen Chan
Tak Y. Leung
Tze K. Lau
Pimlak Charoenkwan
Katherine C.K. Chow
Wyatt Y.W. Lo
Chanane Wanapirak
Torpong Sanguansermsri
Charles R. Cantor
Rossa W.K. Chiu
Y. M.Dennis Lo
Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
description Prenatal diagnosis of monogenic diseases, such as cystic fibrosis and β-thalassemia, is currently offered as part of public health programs. However, current methods based on chorionic villus sampling and amniocentesis for obtaining fetal genetic material pose a risk to the fetus. Since the discovery of cell-free fetal DNA in maternal plasma, the noninvasive prenatal assessment of paternally inherited traits or mutations has been achieved. Due to the presence of background maternal DNA, which interferes with the analysis of fetal DNA in maternal plasma, noninvasive prenatal diagnosis of maternally inherited mutations has not been possible. Here we describe a digital relative mutation dosage (RMD) approach that determines if the dosages of the mutant and wild-type alleles of a disease-causing gene are balanced or unbalanced in maternal plasma. When applied to the testing of women heterozygous for the CD41/42 (-CTTT) and hemoglobin E mutations on HBB, digital RMD allows the fetal genotype to be deduced. The diagnostic performance of digital RMD is dependent on interplay between the fractional fetal DNA concentration and number of DNA molecules in maternal plasma. To achieve fetal genotype diagnosis at lower volumes of maternal plasma, fetal DNA enrichment is desired. We thus developed a digital nucleic acid size selection (NASS) strategy that effectively enriches the fetal DNA without additional plasma sampling or experimental time. We show that digital NASS can work in concert with digital RMD to increase the proportion of cases with classifiable fetal genotypes and to bring noninvasive prenatal diagnosis of monogenic diseases closer to reality. © 2008 by The National Academy of Sciences of the USA.
format Journal
author Fiona M.F. Luna
Nancy B.Y. Tsui
K. C.Allen Chan
Tak Y. Leung
Tze K. Lau
Pimlak Charoenkwan
Katherine C.K. Chow
Wyatt Y.W. Lo
Chanane Wanapirak
Torpong Sanguansermsri
Charles R. Cantor
Rossa W.K. Chiu
Y. M.Dennis Lo
author_facet Fiona M.F. Luna
Nancy B.Y. Tsui
K. C.Allen Chan
Tak Y. Leung
Tze K. Lau
Pimlak Charoenkwan
Katherine C.K. Chow
Wyatt Y.W. Lo
Chanane Wanapirak
Torpong Sanguansermsri
Charles R. Cantor
Rossa W.K. Chiu
Y. M.Dennis Lo
author_sort Fiona M.F. Luna
title Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
title_short Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
title_full Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
title_fullStr Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
title_full_unstemmed Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
title_sort noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on dna in maternal plasma
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=58149401202&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/60754
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