Noninvasive Detection of Twin Zygosity Using Genome-wide Linkage Disequilibrium Information
Prenatal Genetics
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Primary Categories:
- Prenatal Genetics
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Secondary Categories:
- Prenatal Genetics
Introduction:
Twin zygosity assessment provides valuable information for interpreting obstetrics care and pregnancy decisions. The current detection methods for the twin zygosity, including ultrasound scanning and amniocentesis, are nondiagnostic and invasive. This study aimed to develop a novel method to detect zygosity and determine fetal fraction by linked-single nucleotide polymorphism (SNP) in twin pregnancies.
Methods:
SNP‐based noninvasive zygosity assessment has been proven to be highly clinically applicable. The methodology developed the Linkage Disequilibrium information-based noninvasive zygosity (LDNZ) assessment for twin pregnancies, incorporating only 1035 SNPs. Linked SNP increased data robustness, and Linkage Disequilibrium-block directly detected fetal genotypes in the cfDNA. We compared the LDNZ method and SNP-based method for zygosity assessment.
Results:
Fifty-five twin pregnancies were recruited for twin zygosity assessment, with results showing 100% consistency (55/55) with STR typing. LNDZ zygosity assessment revealed 28 cases of dizygotic twins and 27 cases of monozygotic twins. The average informative block for dizygotic twins was 28, and the average for monozygotic twins was 0. We compared LDNZ method and SNP-based method for zygosity assessments. The sensitivity and specificity of the LDNZ method were 1, while the classical SNP-based method misdiagnosed seven monozygotic twins as dizygotic twins. Additionally, the total fetal fraction of monozygotic twins ranged from 8.56% to 25.52%, with an average of 17.03%. Dizygotic twins exhibited a total fetal fraction ranging from 8.12% to 25.02%, with an average total fetal fraction of 15.48%. The average lower individual fetal fraction was 6.31%, while the higher fetal fraction averaged 9.17%.
Conclusion:
Results suggest that LDNZ has the potential to simultaneously perform paternity testing, noninvasive twin zygosity assessment, and fetal fraction determination for twins. Although further prospective validation of this method is needed in a large clinical cohort, LDNZ achieves high performance and outperforms existing methods in the twin zygosity estimation.
Twin zygosity assessment provides valuable information for interpreting obstetrics care and pregnancy decisions. The current detection methods for the twin zygosity, including ultrasound scanning and amniocentesis, are nondiagnostic and invasive. This study aimed to develop a novel method to detect zygosity and determine fetal fraction by linked-single nucleotide polymorphism (SNP) in twin pregnancies.
Methods:
SNP‐based noninvasive zygosity assessment has been proven to be highly clinically applicable. The methodology developed the Linkage Disequilibrium information-based noninvasive zygosity (LDNZ) assessment for twin pregnancies, incorporating only 1035 SNPs. Linked SNP increased data robustness, and Linkage Disequilibrium-block directly detected fetal genotypes in the cfDNA. We compared the LDNZ method and SNP-based method for zygosity assessment.
Results:
Fifty-five twin pregnancies were recruited for twin zygosity assessment, with results showing 100% consistency (55/55) with STR typing. LNDZ zygosity assessment revealed 28 cases of dizygotic twins and 27 cases of monozygotic twins. The average informative block for dizygotic twins was 28, and the average for monozygotic twins was 0. We compared LDNZ method and SNP-based method for zygosity assessments. The sensitivity and specificity of the LDNZ method were 1, while the classical SNP-based method misdiagnosed seven monozygotic twins as dizygotic twins. Additionally, the total fetal fraction of monozygotic twins ranged from 8.56% to 25.52%, with an average of 17.03%. Dizygotic twins exhibited a total fetal fraction ranging from 8.12% to 25.02%, with an average total fetal fraction of 15.48%. The average lower individual fetal fraction was 6.31%, while the higher fetal fraction averaged 9.17%.
Conclusion:
Results suggest that LDNZ has the potential to simultaneously perform paternity testing, noninvasive twin zygosity assessment, and fetal fraction determination for twins. Although further prospective validation of this method is needed in a large clinical cohort, LDNZ achieves high performance and outperforms existing methods in the twin zygosity estimation.