Biology subjects

Mathias Ehrich

Publications and source records attributed to Mathias Ehrich.

2 recordsLinked to original sources

bioRxiv2015

Clinical Validation of a Non-Invasive Prenatal Test for Genome-Wide Detection of Fetal Copy Number Variants

1.BackgroundCurrent cell-free DNA (cfDNA) assessment of fetal chromosomes does not analyze and report on all chromosomes. Hence, a significant proportion of fetal chromosomal abnormalities are not detectable by current non-invasive methods. Here we report the clinical validation of a novel NIPT designed to detect genome-wide gains and losses of chromosomal material [≥]7 Mb and losses associated with specific deletions <7 Mb.\n\nObjectiveThe objective of this study is to provide a clinical validation of the sensitivity and specificity of a novel NIPT for detection of genome-wide abnormalities.\n\nStudy DesignThis retrospective, blinded study included maternal plasma collected from 1222 study subjects with pregnancies at increased risk for fetal chromosomal abnormalities that were assessed for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), fetal sex, genome-wide copy number variants (CNVs) 7 Mb and larger, and select deletions smaller than 7 Mb. Performance was assessed by comparing test results with findings from G-band karyotyping, microarray data, or high coverage sequencing.\n\nResultsClinical sensitivity within this study was determined to be 100% for T21, T18, T13, and SCAs, and 97.7% for genome-wide CNVs. Clinical specificity within this study was determined to be 100% for T21, T18, and T13, and 99.9% for SCAs and CNVs. Fetal sex classification had an accuracy of 99.6%.\n\nConclusionThis study has demonstrated that genome-wide non-invasive prenatal testing (NIPT) for fetal chromosomal abnormalities can provide high resolution, sensitive, and specific detection of a wide range of sub-chromosomal and whole chromosomal abnormalities that were previously only detectable by invasive karyotype analysis. In some instances, this NIPT also provided additional clarification about the origin of genetic material that had not been identified by invasive karyotype analysis.

Genomics↗

bioRxiv2014

Whole Genome Bisulfite Sequencing of Cell Free DNA and its Cellular Contributors Uncovers Placenta Hypomethylated Domains

BackgroundCirculating cell free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the genetically distinct maternal and fetal DNA. Current testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA and thus support additional clinical opportunities; however, this depends on knowledge of the methylomes of ccf DNA and its cellular contributors.\n\nResultsWhole genome bisulfite sequencing was performed on a set of unmatched samples including ccf DNA from 8 non-pregnant (NP) and 7 pregnant female donors and genomic DNA from 7 maternal buffy coat and 5 placenta samples. We found CpG cytosines within longer fragments were more likely to be methylated, linking DNA methylation and fragment size in ccf DNA. Comparison of the methylomes of placenta and NP ccf DNA revealed many of the 51,259 identified differentially methylated regions (DMRs) were located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases, regions we termed placenta hypomethylated domains (PHDs). We found PHDs were consistently located within regions exhibiting low CpG and gene density. DMRs identified when comparing placenta to NP ccf DNA were recapitulated in pregnant ccf DNA, confirming the ability to detect differential methylation in ccf DNA mixtures.\n\nConclusionsWe generated methylome maps for four sample types at single base resolution, identified a link between DNA methylation and fragment length in ccf DNA, identified DMRs between sample groups, and uncovered the presence of megabase-size placenta hypomethylated domains. Furthermore, we anticipate these results to provide a foundation to which future studies using discriminatory DNA methylation may be compared.

Genomics↗