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A simple method to allow for guanine-cytosine amplification error in prenatal DNA screening for trisomy 18.
Clin Chim Acta 2019; 496:13-17CC

Abstract

BACKGROUND

A source of error in prenatal screening for trisomies is PCR amplification error associated with guanine-cytosine (GC) content of DNA fragments in maternal plasma. We describe a simple method of allowing for this.

METHODS

Data from a Reflex DNA screening programme (67 trisomy 18 and 83 unaffected pregnancies) were used to compare the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts (because chromosome 8 has a similar GC content to chromosome 18) with the percentage of chromosome 18 DNA counts using counts from all autosomes in the denominator, with and without an all autosome correction for the GC content of the DNA fragments.

RESULTS

A chromosome 18 to 8 ratio of DNA fragment counts was more discriminatory than the percentage of all autosome counts arising from chromosome 18 without, or with an all autosome correction for GC content bias. It achieves a high screening performance, eg. for a 0.25% false-positive rate, a 97% detection rate instead of 49% without a correction for GC content, and 91% with an all autosome correction for GC content.

CONCLUSION

Consideration can be given to using the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts in cell-free DNA prenatal screening for trisomy 18, avoiding the need for more complex methods of making a correction for the GC content currently used.

Authors+Show Affiliations

Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Electronic address: n.j.wald@qmul.ac.uk.Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31211945

Citation

Wald, Nicholas J., et al. "A Simple Method to Allow for Guanine-cytosine Amplification Error in Prenatal DNA Screening for Trisomy 18." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 496, 2019, pp. 13-17.
Wald NJ, Bestwick JP, Lau KW, et al. A simple method to allow for guanine-cytosine amplification error in prenatal DNA screening for trisomy 18. Clin Chim Acta. 2019;496:13-17.
Wald, N. J., Bestwick, J. P., Lau, K. W., Huttly, W. J., Ke, W., Cheng, R., & Old, R. W. (2019). A simple method to allow for guanine-cytosine amplification error in prenatal DNA screening for trisomy 18. Clinica Chimica Acta; International Journal of Clinical Chemistry, 496, pp. 13-17. doi:10.1016/j.cca.2019.06.015.
Wald NJ, et al. A Simple Method to Allow for Guanine-cytosine Amplification Error in Prenatal DNA Screening for Trisomy 18. Clin Chim Acta. 2019;496:13-17. PubMed PMID: 31211945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A simple method to allow for guanine-cytosine amplification error in prenatal DNA screening for trisomy 18. AU - Wald,Nicholas J, AU - Bestwick,Jonathan P, AU - Lau,King Wai, AU - Huttly,Wayne J, AU - Ke,Weilin, AU - Cheng,Ray, AU - Old,Robert W, Y1 - 2019/06/15/ PY - 2019/03/25/received PY - 2019/06/05/revised PY - 2019/06/13/accepted PY - 2019/6/19/pubmed PY - 2019/6/19/medline PY - 2019/6/19/entrez KW - Cell-free DNA KW - Edwards syndrome KW - GC content KW - Prenatal screening KW - Trisomy 18 SP - 13 EP - 17 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin. Chim. Acta VL - 496 N2 - BACKGROUND: A source of error in prenatal screening for trisomies is PCR amplification error associated with guanine-cytosine (GC) content of DNA fragments in maternal plasma. We describe a simple method of allowing for this. METHODS: Data from a Reflex DNA screening programme (67 trisomy 18 and 83 unaffected pregnancies) were used to compare the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts (because chromosome 8 has a similar GC content to chromosome 18) with the percentage of chromosome 18 DNA counts using counts from all autosomes in the denominator, with and without an all autosome correction for the GC content of the DNA fragments. RESULTS: A chromosome 18 to 8 ratio of DNA fragment counts was more discriminatory than the percentage of all autosome counts arising from chromosome 18 without, or with an all autosome correction for GC content bias. It achieves a high screening performance, eg. for a 0.25% false-positive rate, a 97% detection rate instead of 49% without a correction for GC content, and 91% with an all autosome correction for GC content. CONCLUSION: Consideration can be given to using the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts in cell-free DNA prenatal screening for trisomy 18, avoiding the need for more complex methods of making a correction for the GC content currently used. SN - 1873-3492 UR - https://www.unboundmedicine.com/medline/citation/31211945/A_simple_method_to_allow_for_guanine-cytosine_amplification_error_in_prenatal_DNA_screening_for_trisomy_18 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(19)31907-2 DB - PRIME DP - Unbound Medicine ER -