Supporting Information Yin et al. 10.1073/pnas.1518151112 Fig. S1. Characteristic Z scores of a section of DNA encompassing a deletion in sample 14,945 at (A) varying concentrations of abnormal DNA at 5 million and (B) varying sequencing depths at 15% concentration of abnormal DNA. (C) The acgh plot of sample 14,945 is shown for comparison. 1of5
Fig. S2. Distribution of fetal DNA concentrations estimated of maternal plasma in a cohort of 1,476 pregnant women at various gestational ages. Table S1. s of newborns with DNA deletions and duplications 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 14,416 Dup Chr22 48219551 49451468 1.2 Phelan Mcdermid Syndrome/22q13 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 14,209 Del Chr17 15549649 18845678 3.3 Potocki Lupski Syndrome (17p11.2 duplication ) 14,181 Del Chr2 32444 3562673 3.5 Uncertain 14,777 Del Chr22 17900000 22200000 4.3 DiGeorge Syndrome/22q11.2 14,095 Del Chr16 46271 4904686 4.9 Rubinstein Taybi 14,540 Del Chr15 21250794 26199055 4.9 Prader Willi/Angelman 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 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 14,873 Dup Chr2 161423992 176132164 14.7 2q31.1 Duplication 14,452 Dup Chr15 80043155 100282878 20.2 15q25 Deletion 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 Chr, chromosome; Del, deletion; Dup, duplication. 2of5
Table S2. Comparison of NIPT and acgh in clinical samples A0587 Del Chr16:29673954 30198600 0.52 16p11.2 Microduplication 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 9.76 No No No No A1005 Dup Chr22:22069437 23318455 1.25 22q11.2 Deletion 19.82 Chr22:22000000 23000000 No No Yes Yes A1102 Dup Chr2:88015932 89387655 1.37 20.53 Chr2:88000000 90000000 Yes Yes Yes Yes A1444 Del Chr17:72364514 73777326 1.41 17q25 Duplication 16.93 Chr17:71000000 73000000 No No Yes Yes A0187 Del Chrx:6500000 8000000 1.5 Steroid sulphatase NA Chrx:5000000 7000000 Yes Yes Yes Yes A0197 Dup Chrx:6500000 8000000 1.5 Steroid sulphatase 9.61 Chrx:6000000 7000000 Yes Yes Yes Yes A0403 Del Chrx:6490000 8040000 1.55 Steroid sulphatase 10.58 Chrx:5000000 7000000 Yes Yes Yes Yes A1042 Dup Chr18:587754 2180664 1.59 18p11.32-p11.31 Duplication 18.42 Chr18:0 2000000 No No Yes Yes A1138 Dup Chr18:36319629 37915204 1.60 18q12.2 21.1 Deletion 17.27 Chr18:35000000 37000000 No No Yes Yes A0495 Dup Chr16:14408492 16089759 1.68 16p13.11 Microdeletion 20.54 Chr16:14000000 16000000 Yes Yes Yes Yes A1285 Del Chr17:31461588 33242217 1.78 21.65 Chr17:31000000 33000000 No No Yes Yes A0844 Dup Chr8:1.44e+08 1.46e+08 1.85 8q22.1-qter Duplication 10.42 No No No No A1034 Del Chr4:27770182 29952659 2.18 14q11-q22 Deletion 15.77 Chr4:27000000 29000000 No No Yes Yes A0248 Del Chr4:91399112 93621545 2.22 25.90 Chr4:90000000 92000000 Yes Yes Yes Yes A0129 Dup Chr4:1.57e+08 1.60e+08 2.42 4q32.1-q32.2 Triplication A0769 Del Chr22:17299942 19770514 2.47 DiGeorge Syndrome/22q11.2 A0286 Dup Chr22:18919942 21440514 2.52 DiGeorge Syndrome/22q11.2 14.98 Chr4:157000000 159000000 Yes Yes Yes Yes NA No No No No 13.05 Chr22:20000000 22000000 Yes Yes Yes Yes A0686 Del Chr6:170426 2753293 2.58 6pter-p24 Deletion NA Chr6:0 3000000 No No Yes Yes A0901 Del Chr13:65054495 67810584 2.76 28.55 Chr13:65000000 67000000 No No Yes Yes A0786 Dup Chr21:44077514 46847409 2.77 22.78 Chr21:44000000 47000000 No No Yes Yes A0301 Del Chr2:1.72e+08 1.75e+08 3 31.85 Chr2:171000000 174000000 Yes Yes Yes Yes A0310 Del Chr22:17096855 20311763 3.21 DiGeorge Syndrome/22q11.2 14.74 Chr22:26000000 30000000 Yes Yes Yes Yes A0580 Dup Chr11:1.31e+08 1.35e+08 3.39 Jacobsen Syndrome 8.68 Chr11:131000000 135000000 No No Yes Yes A1052 Dup Chry:6688691 10511314 3.82 17.85 Chry:6000000 10000000 Yes Yes Yes Yes A0001 Del Chr1:814245 4882747 4.07 1p36 Micro 19.05 Chr1:1000000 3000000 Yes Yes Yes Yes A0109 Dup Chr17:16429920 20667174 4.24 Smith Magenis Syndrome 18.88 Chr17:16000000 19000000 Yes Yes Yes Yes A0142 Del Chr22:17900000 22200000 4.3 DiGeorge Syndrome/22q11.2 11.83 Chr22:170000000 22000000 No Yes Yes Yes A1012 Del Chr1:749625 5619192 4.87 1p36.33 36.32 Deletion 14.72 Chr1:0 5000000 Yes Yes Yes Yes 3of5
Table S2. Cont. A0844 Del Chr21:41935392 46880878 4.95 10.42 Chr21:41000000 47000000 No No Yes Yes A0901 Dup Chry:17801068 22916805 5.12 AZFb NA Chry:20000000 23000000 Yes Yes Yes Yes A0433 Dup Chr15:23076361 28436403 5.36 15q11.2 Deletion 20.75 Chr15:23000000 27000000 Yes Yes Yes Yes A0899 Del Chr6:1.65e+08 1.71e+08 5.37 Microdeletion 6q27 anosmia 8.93 Chr6:164000000 171000000 No Yes Yes Yes A0947 Dup Chr15:20627802 26109998 5.48 Prader Willi Syndrome (type 2) 14.76 Chr15:20000000 27000000 Yes Yes Yes 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 Yes Yes A0202 Dup Chr22:17096855 25153910 8.06 DiGeorge Syndrome/22q11.2 24.87 Chr22:17000000 23000000 Yes Yes Yes Yes A0894 Dup Chr3:1.90e+08 1.99e+08 9.13 3q29 Micro 28.29 Chr3:190000000 199000000 Yes Yes Yes Yes A0786 Del Chr4:61552 9237101 9.18 Wol Hirschhorn Syndrome 22.78 Chr4:0 9000000 Yes Yes Yes Yes A0107 Dup Chry:12571053 22916805 10.35 AZFa 23.31 Chry:5000000 8000000 Yes Yes Yes Yes A0107 Del Chry:1091 10379571 10.38 Sex-determining region Y/SRY 23.31 Chry:5000000 8000000 Yes Yes Yes Yes A0011 Del Chr4:61660 10975146 10.91 Wolf Hirschhorn Syndrome 20.89 Chr4:0 12000000 Yes Yes Yes Yes A0256 Dup Chr12:45001 11278012 11.23 12p13.33 Microdeletion 19.27 Chr12:0 13000000 Yes Yes Yes Yes A0578 Del Chr18:10001 11497100 11.49 18p Deletion 14.16 Chr18:3000000 11000000 Yes Yes Yes Yes A0676 Del Chr4:1.78e+08 1.91e+08 12.6 ASD; small omphalocele, 8.54 Chr4:180000000 189000000 Yes Yes Yes Yes anteriorly placed anus, cleft palate A0248 Del Chr4:75392078 88436655 13.04 4q21 Deletion 25.90 Chr4:75000000 92000000 Yes Yes Yes Yes A0577 Dup Chr18:10001 13279511 13.27 18p Deletion 11.13 Chr18:0 8000000 Yes Yes Yes Yes A0856 Del Chr13:1.01e+08 1.14e+08 13.29 17.84 Chr13:101000000 113000000 Yes Yes Yes Yes A0322 Dup Chr17:87009 13501809 13.41 17p13.1 Deletion NA Chr17:0 13000000 Yes Yes Yes Yes A0359 Del Chr18:142096 13885315 13.74 18p Deletion 15.81 Chr18:0 13000000 Yes Yes Yes Yes A0652 Dup Chr13:99103482 1.13e+08 14.32 22.09 Chr13:50000000 95000000 Yes Yes Yes Yes A1092 Dup Chr18:4316 14918854 14.91 18p11.32-p11.31 Duplication 12.48 Chr18:0 15000000 Yes Yes Yes Yes A0580 Del Chr15:83800036 99660791 15.86 15q25 Deletion 8.68 Chr15:69000000 100000000 Yes Yes Yes Yes A0310 Dup Chr11:1.17e+08 1.35e+08 18.14 Jacobsen 14.74 Chr11:116000000 131000000 Yes Yes Yes Yes A0953 Del Chr4:61552 18242617 18.18 4p16.3 16.1 Deletion 9.45 Chr4:0 18000000 Yes Yes Yes Yes A0676 Dup Chr3:93949 19556862 19.46 3p Syndrome 8.54 Chr3:0 20000000 Yes Yes Yes Yes A0856 Dup Chr5:204737 20929211 20.72 Cri du Chat Syndrome 17.84 Chr5:7000000 21000000 Yes Yes Yes Yes (5p deletion) A0686 Dup Chr10:1.14e+08 1.35e+08 21.26 10q26 Deletion NA Chr10:113000000 133000000 Yes Yes Yes Yes A0224 Dup Chr7:1.37e+08 1.59e+08 22.01 17.61 Chr7:135000000 157000000 Yes Yes Yes Yes A1073 Dup Chr2:161989273 185124629 23.14 2q31.1 Duplication 9.78 Chr2:163000000 180000000 Yes Yes Yes Yes A0202 Dup Chr7:1.36e+08 1.59e+08 23.16 24.87 Chr7:136000000 157000000 Yes Yes Yes Yes A0359 Del Chr18:53764221 77982126 24.22 18q Deletion 15.81 Chr18:53000000 76000000 Yes Yes Yes Yes A0302 Dup Chr13:90000001 1.15e+08 25.17 19.03 Chr13:91000000 113000000 Yes Yes Yes Yes A0644 Del Chr13:37474970 65394654 27.92 13q14 Deletion 14.70 Chr13:40000000 66000000 Yes Yes Yes Yes A0224 Dup Chr13:80744674 1.13e+08 32.68 17.61 Chr13:82000000 113000000 Yes Yes Yes Yes A0894 Del Chr13:74724554 1.14e+08 39.35 28.29 Chr13:81000000 113000000 Yes Yes Yes Yes A0256 Dup Chr14:20472548 64879219 44.41 14q11-q22 Deletion 19.27 Chr14:20000000 62000000 Yes Yes Yes Yes 4of5
Table S2. Cont. A0519 Dup Chr18:33381218 783231 17 44.94 18q Deletion 9.57 Chr18:33000000 76000000 Yes Yes Yes Yes A0093 Dup Chr5:0 46100000 46.1 Cri du Chat Syndrome NA Chr5:1000000 45000000 Yes Yes Yes Yes (5p deletion) A0403 Dup Chr21:1 48129895 48.13 Early-onset Alzheimer 10.58 Chr21:15000000 46000000 Yes Yes Yes Yes disease with cerebral amyloid angiopathy A0322 Del Chrx:61529 48771280 48.71 Xp11.22-p11.23 microduplication NA Chrx:3000000 48000000 Yes Yes Yes Yes A0899 Dup Chr2:1.90e+08 2.43e+08 53.11 2q33.1 Deletion 8.93 Chr2:188000000 241000000 Yes Yes Yes Yes A0971 Del Chrx:90374470 155190083 64.82 Xq26-28 deletion 11.03 Chrx:93000000 150000000 Yes Yes Yes Yes A0632 Dup Chr9:261257 84260002 84 9p Deletion 14.90 Chr9:0 37000000 Yes Yes Yes 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. 5of5