Supplemental Table S1. Basic quality information of exome sequencing experiments for our 6 study subjects.

Individual ID

Mean Seq. Depth

% of varaints with >10 depth

No. of SNVs (Indels)*

5 58 91.2 52,771（5,312）32 59 92.1 55,503（5,424）142 57 90.3 54,014（5,432）212 57 90.5 53,122（5,234）220 55 88.7 51,234（5,098）356 55 89.5 52,112（5,129）

*after quality control

Supplemental Table S2. Filtering procedure applied to the exome sequencing data from

6 BPD relative cases.

Filtering Procedure Number of Variants pass QC (%)

Genotype calls released 140,814 (100)

Quality Control 114,432 (81.26)

Linkage Peak Region 444 (0.32)

Variants with functional significance 60 (0.04)

Novel variants or variants with MAF less than 0.05 15 (0.01)

The number of variants is reduced to 15 from the 140,814 released by exome sequencing

by applying various filtering strategies.

Supplemental Table S3. 60 variants with potential functional significance.

Chr SNP Start Ref Alt Gene Function AAChanges

1000g_ma

f

SIFT

*

Polyphen2*

*

10

- 8106194

6 C T ZMIZ1 nonsynonymous SNV p.P701L NA D P

10

rs200388618 8127281

4 G C EIF5AL1 nonsynonymous SNV p.V137L NA D B

10

rs17886395 8131866

3 C G SFTPA2 nonsynonymous SNV p.A91P 0.14 T B

10

rs4253527 8137377

7 C T SFTPA1 nonsynonymous SNV p.R219W 0.1 T B

10

rs2243639 8170172

2 T C SFTPD nonsynonymous SNV p.T180A 0.6 T B

10

rs721917 8170632

4 A G SFTPD nonsynonymous SNV p.M31T 0.41 T B

10

rs1932574 8184169

2 G T TMEM254 nonsynonymous SNV p.C93F 0.41 . .

10

rs1049550 8192670

2 G A ANXA11 nonsynonymous SNV p.R230C 0.44 D D

10 rs2229554 8192705 C T ANXA11 nonsynonymous SNV p.R191Q 0.06 T D

9

10

rs36027713 8212654

1 C G DYDC2 nonsynonymous SNV p.P123R 0.03 T B

10

rs1047951 8212660

0 G A DYDC2 nonsynonymous SNV p.G143S 0.03 T B

10

rs7075840 8236340

4 A G SH2D4B nonsynonymous SNV p.H189R 0.24 T B

10

rs17101193 8474492

6 C A NRG3 nonsynonymous SNV p.N552K 0.05 T B

10

- 8590249

7 A T GHITM nonsynonymous SNV p.E72D NA T B

10

rs12781048 8595626

8 C A CDHR1 nonsynonymous SNV p.H53Q 0.05 T B

10

rs45584033 8597423

1 C T CDHR1 nonsynonymous SNV p.P812S 0.04 D D

10

rs6585847 8598180

1 T G LRIT2 nonsynonymous SNV p.T510P 0.47 T B

10

rs12217769 8598184

2 A G LRIT2 nonsynonymous SNV p.V496A 0.22 T B

10 rs11200925 8598432 G A LRIT2 nonsynonymous SNV p.L220F 0.22 T B

3

10

rs3814205 8613105

9 A G CCSER2 nonsynonymous SNV p.N84S 0.21 T B

10

rs11557865 8627324

9 T C CCSER2 nonsynonymous SNV p.S246P 0.21 T B

10

rs2306265 8748438

2 C T GRID1 nonsynonymous SNV p.V529I 0.02 D D

10

rs3812645 8748931

7 T C GRID1 nonsynonymous SNV p.M430V 0.02 T B

10

rs10887621 8827745

7 C T WAPAL nonsynonymous SNV p.V124I 0.28 T B

10

rs2675703 8841456

9 C T OPN4 nonsynonymous SNV p.P10L 0.15 T B

10

rs1079610 8842211

6 C T OPN4 nonsynonymous SNV p.T394I 0.63 T B

10

rs3750823 8871715

4 C T MMRN2 nonsynonymous SNV p.G49S 0.47 T B

10

rs9864 8872239

8 A T SNCG nonsynonymous SNV p.E110V 0.24 T B

10 - 8885434 G C GLUD1 nonsynonymous SNV p.R60G NA T .

9

10

rs77879311 8891184

1 A G FAM35A nonsynonymous SNV p.S244G 0.18 D P

10

rs11202365 8893024

9 A T FAM35A nonsynonymous SNV p.S550C 0.38 D P

10

- 8926522

0 C A MINPP1 nonsynonymous SNV p.S183Y NA T D

10

- 8928087

2 C T MINPP1 nonsynonymous SNV p.T137I NA T B

10

rs17173698 8946895

3 G A PAPSS2 nonsynonymous SNV p.E10K 0.01 T B

10

rs2296545 9034283

7 C G RNLS nonsynonymous SNV p.E37D 0.48 T B

10

rs1409136 9035659

8 A G LIPJ nonsynonymous SNV p.I210V 0.75 T B

10

rs814628 9042965

2 A G LIPF nonsynonymous SNV p.T128A 0.18 D D

10

rs6586145 9043334

5 T A LIPF nonsynonymous SNV p.F191I 0.06 . B

10 rs55788049 9048655 G A LIPK nonsynonymous SNV p.S36N 0.0013 T P

3

10

rs1214464 9051230

6 G C LIPK nonsynonymous SNV p.M331I 0.2 T B

10

rs10788611 9053066

0 C A LIPN nonsynonymous SNV p.T244N 0.35 T B

10

rs12254856 9067302

4 G A STAMBPL1 nonsynonymous SNV p.S196N 0.12 T B

10

rs1051339 9100733

9 C T LIPA nonsynonymous SNV p.G23R 0.1 T B

10

rs1051338 9100736

0 T G LIPA nonsynonymous SNV p.T16P 0.34 T B

10

rs17468739 9106594

9 A C IFIT2 nonsynonymous SNV p.E79A 0.14 T B

10

rs2070845 9106607

5 A G IFIT2 nonsynonymous SNV p.K121R 0.24 T B

10

rs1727 9106676

9 C A IFIT2 nonsynonymous SNV p.D352E 0.77 T B

10

rs1129777 9146892

5 C G KIF20B nonsynonymous SNV p.A50G 0.24 T P

10 rs17484219 9147921 G T KIF20B nonsynonymous SNV p.E490D 0.23 T P

1

10

rs12572012 9148764

9 A T KIF20B nonsynonymous SNV p.N756I 0.24 T P

10

rs3758388 9148897

9 A T KIF20B nonsynonymous SNV p.H789L 0.24 T B

10

rs1062465 9149763

1 T A KIF20B nonsynonymous SNV p.D1011E 0.23 D B

10

rs144593231 9149790

2 -

TAAAA

G KIF20B nonframeshift insertion

p.L1102delinsLK

V 0.23

10

rs1886996 9149812

7 T C KIF20B nonsynonymous SNV p.C1177R 0.74 T B

10

rs1886997 9149825

4 A G KIF20B nonsynonymous SNV p.N1219S 0.23 T B

10

rs34354493 9152254

8 A G KIF20B nonsynonymous SNV p.K1649E 0.23 D P

10

- 9360194

6 A - TNKS2 frameshift deletion p.T619fs NA

10

rs1107947 9366811

0 T A FGFBP3 nonsynonymous SNV p.E206V 0.25 T B

10 - 9399910 A C CPEB3 nonsynonymous SNV p.F334L NA T B

6

10

rs2490741 9459456

5 G A EXOC6 nonsynonymous SNV p.V24I 0.69 T B

* SIFT prediction. T stands for tolerated and D stands for damaging.

** Polyphen2 prediction. B stands for benign, P stands for possibly damaging, and D stands for probably damaging.

Supplemental Figure S1. Significant peak regions identified on chromosome 5 in three

sets of linkage analysis. a. Linkage results for chromosome 5 using SNP set #4 with

10,058 SNPs; b. Linkage results for chromosome 5 using SNP set #6 with 9,715 SNPs; c.

Linkage results for chromosome 5 using SNP set #8 with 10,402 SNPs. Two peak regions

5q33.1- 5q 33.3 and 5q35.1-5q35.2 were identified 3 and 1 times respectively. The LOD

threshold was indicated in dotted line.

Supplemental Figure S2. Significant peak regions identified on chromosome 10 in all

the ten sets of linkage analysis. a. Linkage results for chromosome 10 using SNP set #1

with 10,396 SNPs; b. Linkage results for chromosome 10 using SNP set #2 with 9,648

SNPs; c. Linkage results for chromosome 10 using SNP set #3 with 9,963 SNPs; d.

Linkage results for chromosome 10 using SNP set #4 with 10,058 SNPs; e. Linkage

results for chromosome 10 using SNP set #5 with 10,407 SNPs; f. Linkage results for

chromosome 10 using SNP set #6 with 9,715 SNPs; g. Linkage results for chromosome

10 using SNP set #7 with 10,418 SNPs; h. Linkage results for chromosome 10 using SNP

set #8 with 10,402 SNPs; i. Linkage results for chromosome 10 using SNP set #9 with

10,236 SNPs; j. Linkage results for chromosome 10 using SNP set #10 with 10,402

SNPs. Chromosome region 10q21.1-10q21.2 and 10q23.1-10q23.33 (10q22.3-10q23.33)

were identified multiple times in the 10 replicate sets and 10q23.1-10q23.33 (10q22.3-

10q23.33) was identified repetitively in all of the 10 replicate sets. The LOD threshold

was indicated in dotted line.

Supplemental figure S3. Co-segregation patterns of those 6 highlighted mutations across study subjects. Reference and alternative alleles were indicated as 0 and 1 respectively.