Title: Concurrent Whole-Genome Haplotyping and Copy-Number Profiling of Single Cells
Authors: Zamani Esteki, Masoud
Dimitriadou, Eftychia
Mateiu, Ligia
Melotte, Cindy
Van der Aa, Niels
Kumar, Parveen
Das, Rakhi
Theunis, Koen
Cheng, Jiqiu
Legius, Eric
Moreau, Yves
Debrock, Sophie
D'Hooghe, Thomas
Verdyck, Pieter
De Rycke, Martine
Sermon, Karen
Vermeesch, Joris #
Voet, Thierry # ×
Issue Date: Jun-2015
Publisher: American Society of Human Genetics
Series Title: American Journal of Human Genetics vol:96 issue:6 pages:894-912
Article number: S0002-9297(15)00148-2
Abstract: Methods for haplotyping and DNA copy-number typing of single cells are paramount for studying genomic heterogeneity and enabling genetic diagnosis. Before analyzing the DNA of a single cell by microarray or next-generation sequencing, a whole-genome amplification (WGA) process is required, but it substantially distorts the frequency and composition of the cell's alleles. As a consequence, haplotyping methods suffer from error-prone discrete SNP genotypes (AA, AB, BB) and DNA copy-number profiling remains difficult because true DNA copy-number aberrations have to be discriminated from WGA artifacts. Here, we developed a single-cell genome analysis method that reconstructs genome-wide haplotype architectures as well as the copy-number and segregational origin of those haplotypes by employing phased parental genotypes and deciphering WGA-distorted SNP B-allele fractions via a process we coin haplarithmisis. We demonstrate that the method can be applied as a generic method for preimplantation genetic diagnosis on single cells biopsied from human embryos, enabling diagnosis of disease alleles genome wide as well as numerical and structural chromosomal anomalies. Moreover, meiotic segregation errors can be distinguished from mitotic ones.
ISSN: 0002-9297
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Cytogenetics and Genome Research
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Department of Human Genetics - miscellaneous
Organ Systems (+)
Laboratory of Reproductive Genomics
× corresponding author
# (joint) last author

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