ADVANCED PGT SERVICES

Transcription

1 Genomic Prediction ADVANCED PGT SERVICES

2 with PGT-A using SEQ is a cost-effective, rigorously validated, unambiguous, and streamlined test for aneuploidy in blastocyst biopsies, and uses state of the art next generation sequencing

3 Accuracy/Concordance embryo rebiopsies (n=98) cell lines (n=377) 98% >99% Overall accuracy on cell lines and concordance on embryo trophectoderm rebiopsies using SEQ. 5 1 Examples of copy number data from positive control cell lines using SEQ X Y ,XY 3 5 COPY NUMBER X Y CHROMOSOME X Y ,XX, COPY NUMBER X Y CHROMOSOME

4 Use of SEQ genotype data to distinguish pure from greater than or equal to 2% contamination.44 ALLELE RATIO % 2% 1% 5% % AMOUNT OF CONTAMINATION.8 Ability of SEQ to distinguish related from unrelated biopsies using genotyping data SIMILARITY siblings unrelated

5 Detection of triploidy using SEQ on cell lines and embryo trophectoderm rebiopsies using genotyping data ALLELE RATIO.4.36 cell line diploid cell line triploid embryo diploid embryo triploid TRIPLOID STATUS Mosaicism can be detected down to 4% with SEQ OBSERVED COPY NUMBER (.1,.5] (.5,.9] (.9,1.1] (1.1,1.5] (1.5,1.9] (1.9,2.1] (2.1,2.5] (2.5,2.9] (2.9,3.1] (3.1,3.5] EXPECTED COPY NUMBER

6 EP T uses genome wide genotypes and copy numbers to provide the first opportunity for simultaneous testing of aneuploidy (PGT-A), monogenic disorders (PGT-M), polygenic risks (PGT-P), and structural abnormalities (PGT-S)

7 Accuracy/Concordance PGT-P (Hypothyroidism) PGT-A PGT-S (> 3.5Mb) PGT-M 83% >99% >99% >99.9% Overall accuracy/concordance using EP T (PGT-A, -M, -P, and -S) 5 1 Example results of PGT-A using EP T GM326 GM125 GM9286 +X XYY +9 GM2948 GM3184 GM GM1315 GM7826 GM normal male normal female

8 Normal Abnormal >99% accuracy of SEQ PGT-A using positive control cell lines Normal Abnormal 152 (TN) (FN) 3 (FP) 72 (TP) ACTUAL STATE EXPERIMENTAL RESULTS Normal Abnormal Results of validation (1% accuracy) on positive controls using EP T based prediction of cystic fibrosis delta F58 status (PGT-M) Normal Abnormal 11 (TN) (FN) (FP) 96 (TP) ACTUAL STATE EXPERIMENTAL RESULTS Normal Abnormal 83% accuracy for predicting hypothyroidism using EP T (PGT-P) Note: Heritability studies suggest that up to 67% of hypothyroidism is genetically determined. Normal Abnormal 21 (TN) 5 (FN) 1 (FP) 9 (TP) ACTUAL STATE EXPERIMENTAL RESULTS

9 Strategy using mendelian inheritance rules to determine which nearby SNPs in the carrier parent are informative of mutational status in embryos Genotyping Data Haplotype Inference Embryo Predictions SNP ID Father Mother Reference Child SNP ID Father Mother Child SNP ID Carrier Normal SNP1 AB AA AA SNP1 A B A A A A SNP1 A A B A SNP2 AA AA AA SNP2 SNP2 SNP3 AB BB BB SNP3 B A B B B B SNP3 B B A B SNP4 AB AA AB SNP4 B A A A B A SNP4 B A A A SNP5 AB AB AA SNP5 SNP5 deltaf58 AB AA AB deltaf58 B A A A B A deltaf58 B A A A SNP6 AB BB BB SNP6 B A B B B B SNP6 B B A B SNP7 AB BB BB SNP7 B A B B B B SNP7 B B A B SNP8 AA AA AA SNP8 SNP8 SNP9 BB BB BB SNP9 SNP9 SNP1 AB AA AA SNP1 A B A A A A SNP1 A A B A mutation locus (obtained from prior test results) paternal mutation chr informative paternal normal chr not informative maternal chr

10 Validation of EP T based prediction of hypothyroidism using 4945 SNPs identified from the UK BioBank dataset 2 4 SAMPLE SIZE UKBB Training Set HYPOTHYROIDISM RISK SCORE Test Set (4945 SNPs) Controls Cases Risk Score Threshold Additional intended targets for EP T based prediction of polygenic disorders Type 1 Diabetes Type 2 Diabetes Coronary Artery Disease Atrial Fibrillation Breast Cancer Hypothyroidism Mental Disability Ideopathic Short Stature Inflammatory Bowel Disease Chronic Kidney Disease SAMPLE SIZE Controls Cases

11 >99% accuracy of predicting segmental aneuploidy down to 3.5 million basepairs (MBp) in positive controls using EP T (PGT-S). 2.5 AVERAGE COPY NUMBER SIZE IN MBP within the deletion outside the deletion Pricing and case management with Genetic counseling Requisition completed online Consent easily uploaded Report online < 7 days < 14 days $15/case $2/embryo $1/case $4/embryo

12 genomicprediction.com Genomic Prediction Clinical Laboratory 675 US Highway One North Brunswick, NJ CLIA License Number: 31D NJDOH Clinical Laboratory License Number: CLIS Number: Participant: AAB PGS Proficiency Testing Program Account Number: CE Mark Approved