Supporting Information
Yin et al. 10.1073/pnas.1518151112
Fig. S1. CharacteristicZscores of a section of DNA encompassing a deletion in sample 14,945 at (A) varying concentrations of abnormal DNA at 5 million reads
Fig. S2. Distribution of fetal DNA concentrations estimated by NIPT of maternal plasma in a cohort of 1,476 pregnant women at various gestational ages.
Table S1. aCGH results of newborns with DNA deletions and duplications
Sample
identification Dup/del Chr Start End Size (Mb) Syndrome annotation 14,437 Del Chr16 14956252 16157108 1.2 16p13.11 Microdeletion (neurocognitive disorder
susceptibility locus)
14,394 Del Chr1 145031367 146253330 1.2 Thrombocytopenia-absent radius syndrome
14,416 Dup Chr22 48219551 49451468 1.2 Phelan–Mcdermid Syndrome/22q13 deletion syndrome 14,452 Del Chr5 204737 1726099 1.5 Cri du Chat Syndrome (5p deletion)
14,944 Del Chr19 11693072 13505798 1.8 Uncertain 14,095 Del Chr21 44565059 46880878 2.3 Uncertain
14,368 Del Chrx 31012571 33514518 2.5 Xp21 deletion syndrome
14,209 Del Chr17 15549649 18845678 3.3 Potocki–Lupski Syndrome (17p11.2 duplication syndrome) 14,181 Del Chr2 32444 3562673 3.5 Uncertain
14,777 Del Chr22 17900000 22200000 4.3 DiGeorge Syndrome/22q11.2 deletion syndrome 14,095 Del Chr16 46271 4904686 4.9 Rubinstein–Taybi syndrome
14,540 Del Chr15 21250794 26199055 4.9 Prader–Willi/Angelman syndrome 14,883 Del Chr3 137461910 143694820 6.2 Uncertain
14,157 Del Chr13 96437228 103424298 7 Uncertain
14,119 Del Chr18 50413206 58403399 8 18q Deletion syndrome
14,159 Del Chr10 183492 11035280 10.9 Hypoparathyroidism, sensorineural deafness, and renal disease (HDRS)
14,115 Del Chr4 133413 13498201 13.4 Wolf–Hirschhorn syndrome 14,873 Dup Chr2 161423992 176132164 14.7 2q31.1 Duplication syndrome 14,452 Dup Chr15 80043155 100282878 20.2 15q25 Deletion syndrome 14,945 Del Chr1 115862191 136892070 21 Uncertain
14,798 Del Chr1 156153073 182952784 26.8 Uncertain
14,181 Dup Chr9 261257 31357372 31.1 9p Deletion syndrome
Ta ble S2. Com pariso n o f N IPT and aCG H in clinical sa mples Sample identification aCGH result Syndrome associated with region* NIPT result Dup/del Location p redicted by aCGH Size (Mb) FC (%) Location p redicted by NIPT 3 M illion reads 5 M illion reads 10 Million reads 15 Million reads A0587 Del Chr16:29673954 – 30198600 0.52 16p11.2 M icroduplication syndrome 17.01 — No No No No A0133 Dup Chr19:327273 – 863312 0.54 2.01 — No No No No A0553 Del Chr19:3806228 – 4343253 0.54 11.61 — No No No No A0519 Del Chr3:27275 – 853692 0.83 3p Syndrome 9.57 — No No No No A0957 Del Chr7:157683596 – 158602499 0.92 7q36.1 – 36.3 Deletion 10.34 — No No No No A0281 Del Chr17:674618 – 1859251 1.18 17p13.1 Deletion syndrome 9.76 — No No No No A1005 Dup Chr22:22069437 – 23318455 1.25 22q11.2 Deletion syndrome 19.82 Chr22:22000000 – 23000000 No No Yes Y es A1102 Dup Chr2:88015932 – 89387655 1.37 20.53 Chr2:88000000 – 90000000 Yes Yes Y es Yes A1444 Del Chr17:72364514 – 73777326 1.41 17q25 Duplication 16.93 Chr17:71000000 – 73000000 No No Yes Y es A0187 Del Chrx:6500000 – 8000000 1.5 Steroid sulphatase deficiency (STS) NA Chrx:5000000 – 7000000 Yes Yes Y es Yes A0197 Dup Chrx:6500000 – 8000000 1.5 Steroid sulphatase deficiency (STS) 9.61 Chrx:6000000 – 7000000 Yes Yes Y es Yes A0403 Del Chrx:6490000 – 8040000 1.55 Steroid sulphatase deficiency (STS) 10.58 Chrx:5000000 – 7000000 Yes Yes Y es Yes A1042 Dup Chr18:587754 – 2180664 1.59 18p11.32-p11.31 Duplication 18.42 Chr18:0 – 2000000 No No Yes Y es A1138 Dup Chr18:36319629 – 37915204 1.60 18q12.2 – 21.1 Deletion 17.27 Chr18:35000000 – 37000000 No No Yes Y es A0495 Dup Chr16:14408492 – 16089759 1.68 16p13.11 Microdeletion 2 0.54 Chr16:14000000 – 16000000 Yes Yes Y es Yes A1285 Del Chr17:31461588 – 33242217 1.78 21.65 Chr17:31000000 – 33000000 No No Yes Y es A0844 Dup Chr8:1.44e + 08 – 1.46e + 08 1.85 8q22.1-qter Duplication syndrome 10.42 — No No No No A1034 Del Chr4:27770182 – 29952659 2.18 14q11-q22 Deletion syndrome 15.77 Chr4:27000000 – 29000000 No No Yes Y es A0248 Del Chr4:91399112 – 93621545 2.22 25.90 Chr4:90000000 – 92000000 Yes Yes Y es Yes A0129 Dup Chr4:1.57e + 08 – 1.60e + 08 2.42 4q32.1-q32.2 Triplication syndrome 14.98 Chr4:157000000 – 159000000 Yes Yes Y es Yes A0769 Del Chr22:17299942 – 19770514 2.47 DiGeorge Syndrome/22q11.2 deletion syndrome NA — No No No No A0286 Dup Chr22:18919942 – 21440514 2.52 DiGeorge Syndrome/22q11.2 deletion syndrome 13.05 Chr22:20000000 – 22000000 Yes Yes Y es Yes A0686 Del Chr6:170426 – 2753293 2.58 6pter-p24 Deletion syndrome NA Chr6:0 – 3000000 No No Yes Y es A0901 Del Chr13:65054495 – 67810584 2.76 28.55 Chr13:65000000 – 67000000 No No Yes Y es A0786 Dup Chr21:44077514 – 46847409 2.77 22.78 Chr21:44000000 – 47000000 No No Yes Y es A0301 Del Chr2:1.72e + 08 – 1.75e + 08 3 31.85 Chr2:171000000 – 174000000 Yes Yes Y es Yes A0310 Del Chr22:17096855 – 20311763 3.21 DiGeorge Syndrome/22q11.2 deletion syndrome 14.74 Chr22:26000000 – 30000000 Yes Yes Y es Yes A0580 Dup Chr11:1.31e + 08 – 1.35e + 08 3.39 Jacobsen Syndrome 8.68 Chr11:131000000 – 135000000 N o N o Y es Yes A1052 Dup Chry:6688691 – 10511314 3.82 17.85 Chry:6000000 – 10000000 Yes Yes Y es Yes A0001 Del Chr1:814245 – 4882747 4.07 1p36 Microdeletion syndrome 19.05 Chr1:1000000 – 3000000 Yes Yes Y es Yes A0109 Dup Chr17:16429920 – 20667174 4.24 Smith – Magenis Syndrome 18.88 Chr17:16000000 – 19000000 Yes Yes Y es Yes A0142 Del Chr22:17900000 – 22200000 4.3 DiGeorge Syndrome/22q11.2 deletion syndrome 11.83 Chr22:170000000 – 22000000 No Yes Y es Yes A1012 Del Chr1:749625 – 5619192 4.87 1p36.33 – 36.32 Deletion 14.72 Chr1:0 – 5000000 Yes Yes Y es Yes
Ta ble S2. Cont. Sample identification aCGH result Syndrome associated with region* NIPT result Dup/del Location p redicted by aCGH Size (Mb) FC (%) Location p redicted by NIPT 3 M illion reads 5 M illion reads 10 Million reads 15 Million reads A0844 Del Chr21:41935392 – 46880878 4.95 10.42 Chr21:41000000 – 47000000 No No Yes Y es A0901 Dup Chry:17801068 – 22916805 5.12 AZFb N A Chry:20000000 – 23000000 Yes Yes Y es Yes A0433 Dup Chr15:23076361 – 28436403 5.36 15q11.2 Deletion syndrome 20.75 Chr15:23000000 – 27000000 Yes Yes Y es Yes A0899 Del Chr6:1.65e + 08 – 1.71e + 08 5.37 Microdeletion 6q27 anosmia 8 .93 Chr6:164000000 – 171000000 N o Y es Yes Y es A0947 Dup Chr15:20627802 – 26109998 5.48 Prader – Willi Syndrome (type 2 ) 14.76 Chr15:20000000 – 27000000 Yes Yes Y es Yes A0133 Del Chr14:1.01e + 08 – 1.07e + 08 6.06 2.01 — No No No No A0001 Dup Chr19:51529057 – 59092570 7.56 19.05 Chr19:50000000 – 57000000 Yes Yes Y es Yes A0202 Dup Chr22:17096855 – 25153910 8.06 DiGeorge Syndrome/22q11.2 deletion syndrome 24.87 Chr22:17000000 – 23000000 Yes Yes Y es Yes A0894 Dup Chr3:1.90e + 08 – 1.99e + 08 9.13 3q29 Microdeletion syndrome 28.29 Chr3:190000000 – 199000000 Yes Yes Y es Yes A0786 Del Chr4:61552 – 9237101 9.18 Wol – Hirschhorn Syndrome 22.78 Chr4:0 – 9000000 Yes Yes Y es Yes A0107 Dup Chry:12571053 – 22916805 10.35 AZFa 23.31 Chry:5000000 – 8000000 Yes Yes Y es Yes A0107 Del Chry:1091 – 10379571 10.38 Sex-determining region Y /SRY 23.31 Chry:5000000 – 8000000 Yes Yes Y es Yes A0011 Del Chr4:61660 – 10975146 10.91 Wolf – Hirschhorn Syndrome 20.89 Chr4:0 – 12000000 Yes Yes Y es Yes A0256 Dup Chr12:45001 – 11278012 11.23 12p13.33 Microdeletion syndrome 19.27 Chr12:0 – 13000000 Yes Yes Y es Yes A0578 Del Chr18:10001 – 11497100 11.49 18p D eletion syndrome 14.16 Chr18:3000000 – 11000000 Yes Yes Y es Yes A0676 Del Chr4:1.78e + 08 – 1.91e + 08 12.6 ASD; small omphalocele, anteriorly placed anus, cleft palate 8.54 Chr4:180000000 – 189000000 Yes Yes Y es Yes A0248 Del Chr4:75392078 – 88436655 13.04 4q21 Deletion syndrome 25.90 Chr4:75000000 – 92000000 Yes Yes Y es Yes A0577 Dup Chr18:10001 – 13279511 13.27 18p D eletion syndrome 11.13 Chr18:0 – 8000000 Yes Yes Y es Yes A0856 Del Chr13:1.01e + 08 – 1.14e + 08 13.29 17.84 Chr13:101000000 – 113000000 Yes Yes Y es Yes A0322 Dup Chr17:87009 – 13501809 13.41 17p13.1 Deletion syndrome NA Chr17:0 – 13000000 Yes Yes Y es Yes A0359 Del Chr18:142096 – 13885315 13.74 18p D eletion syndrome 15.81 Chr18:0 – 13000000 Yes Yes Y es Yes A0652 Dup Chr13:99103482 – 1.13e + 08 14.32 22.09 Chr13:50000000 – 95000000 Yes Yes Y es Yes A1092 Dup Chr18:4316 – 14918854 14.91 18p11.32-p11.31 Duplication 12.48 Chr18:0 – 15000000 Yes Yes Y es Yes A0580 Del Chr15:83800036 – 99660791 15.86 15q25 Deletion syndrome 8.68 Chr15:69000000 – 100000000 Yes Yes Y es Yes A0310 Dup Chr11:1.17e + 08 – 1.35e + 08 18.14 Jacobsen syndrome 14.74 Chr11:116000000 – 131000000 Yes Yes Y es Yes A0953 Del Chr4:61552 – 18242617 18.18 4p16.3 – 16.1 Deletion 9 .45 Chr4:0 – 18000000 Yes Yes Y es Yes A0676 Dup Chr3:93949 – 19556862 19.46 3p Syndrome 8.54 Chr3:0 – 20000000 Yes Yes Y es Yes A0856 Dup Chr5:204737 – 20929211 20.72 Cri du Chat Syndrome (5p deletion) 17.84 Chr5:7000000 – 21000000 Yes Yes Y es Yes A0686 Dup Chr10:1.14e + 08 – 1.35e + 08 21.26 10q26 Deletion syndrome NA Chr10:113000000 – 133000000 Yes Yes Y es Yes A0224 Dup Chr7:1.37e + 08 – 1.59e + 08 22.01 17.61 Chr7:135000000 – 157000000 Yes Yes Y es Yes A1073 Dup Chr2:161989273 – 185124629 23.14 2q31.1 Duplication syndrome 9.78 Chr2:163000000 – 180000000 Yes Yes Y es Yes A0202 Dup Chr7:1.36e + 08 – 1.59e + 08 23.16 24.87 Chr7:136000000 – 157000000 Yes Yes Y es Yes A0359 Del Chr18:53764221 – 77982126 24.22 18q D eletion syndrome 15.81 Chr18:53000000 – 76000000 Yes Yes Y es Yes A0302 Dup Chr13:90000001 – 1.15e + 08 25.17 19.03 Chr13:91000000 – 113000000 Yes Yes Y es Yes A0644 Del Chr13:37474970 – 65394654 27.92 13q14 Deletion syndrome 14.70 Chr13:40000000 – 66000000 Yes Yes Y es Yes A0224 Dup Chr13:80744674 – 1.13e + 08 32.68 17.61 Chr13:82000000 – 113000000 Yes Yes Y es Yes A0894 Del Chr13:74724554 – 1.14e + 08 39.35 28.29 Chr13:81000000 – 113000000 Yes Yes Y es Yes A0256 Dup Chr14:20472548 – 64879219 44.41 14q11-q22 Deletion syndrome 19.27 Chr14:20000000 – 62000000 Yes Yes Y es Yes
Ta ble S2. Cont. Sample identification aCGH result Syndrome associated with region* NIPT result Dup/del Location p redicted by aCGH Size (Mb) FC (%) Location p redicted by NIPT 3 M illion reads 5 M illion reads 10 Million reads 15 Million reads A0519 Dup Chr18:33381218 – 783231 1 7 44.94 18q D eletion syndrome 9.57 Chr18:33000000 – 76000000 Yes Yes Y es Yes A0093 Dup Chr5:0 – 46100000 46.1 Cri du Chat Syndrome (5p deletion) NA Chr5:1000000 – 45000000 Yes Yes Y es Yes A0403 Dup Chr21:1 – 48129895 48.13 Early-onset Alzheimer disease w ith cerebral amyloid angiopathy 10.58 Chr21:15000000 – 46000000 Yes Yes Y es Yes A0322 Del Chrx:61529 – 48771280 48.71 Xp11.22-p11.23 microduplication NA Chrx:3000000 – 48000000 Yes Yes Y es Yes A0899 Dup Chr2:1.90e + 08 – 2.43e + 08 53.11 2q33.1 Deletion syndrome 8.93 Chr2:188000000 – 241000000 Yes Yes Y es Yes A0971 Del Chrx:90374470 – 155190083 64.82 Xq26-28 deletion 11.03 Chrx:93000000 – 150000000 Yes Yes Y es Yes A0632 Dup Chr9:261257 – 84260002 84 9p Deletion syndrome 14.90 Chr9:0 – 37000000 Yes Yes Y es Yes ASD, atrial septal defect; AZFa, azoospermia factor region a; AZFb, azoospermia factor region b; Chr, chromosome; Del, deletion; Dup, duplication; FC, fetal DNA concentration; NA, not applicable. *Syndrome is associated with either deletion or duplication in the region but may not match the observed DNA abnormality.
