Background
Methods
Patients
Whole-exome sequencing
Whole-exome sequencing processing and alignment
Annotation
Sanger sequencing
Results
Whole-exome sequencing in three families with atopic dermatitis
Filter system | Dominant model | |||
---|---|---|---|---|
Filter step | Filter process | Family A | Family B | Family C |
Raw | – | 7523 | 3564 | 3227 |
Filter 1 | EFFECT | 2799 | 2489 | 2198 |
Filter 2 | IMPACT | 502 | 516 | 443 |
Filter 3 | SIFT, PolyPhen2 | 278 | 258 | 231 |
Filter 4 | phyloP | 234 | 225 | 206 |
Filter 5 | Phastcon | 200 | 173 | 156 |
Filter 6 | 1000 genome | 33 | 60 | 53 |
Filter 7 | Korean | 31 | 54 | 49 |
Common variant | Functional prediction program | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene | RS# |
aChr |
bPOS |
cAmino acid change | Type |
dSIFT |
ePolyphen2 |
fPhyloP |
gPhastCons |
hGlobal | East Asian |
iKorean |
COL6A6
| 16830494 | chr3 | 130,361,856 | R1739Q | cSNP | 0.04 | 0.272 | 1.703 | 0.995 | 0.12 | 0.19 | 0.188 |
ANKRD35
| 11579366 | chr1 | 145,562,293 | E661Q | cSNP | 0.38 | 0.971 | 5.285 | 1 | 0.39 | 0.26 | 0.233 |
TUFT1
| 3828054 | chr1 | 151,512,895 | Q18R | cSNP | 0.77 | 0.688 | 1.688 | 0.288 | 0.1 | 0.03 | 0.047 |
TMEM175
| 34311866 | chr4 | 951,947 | M393T | cSNP | 0.01 | 0 | 1.299 | 0.999 | 0.12 | 0.12 | 0.155 |
EDN1
| 5370 | chr6 | 12,296,255 | K198N | cSNP | 0.08 | 0.454 | 0.049 | 0.001 | 0.21 | 0.28 | 0.258 |
NRAP
| 2270182 | chr10 | 115,392,919 | N519I | cSNP | 0.19 | 0.958 | 2.477 | 1 | 0.26 | 0.20 | 0.205 |
HGFAC
| 16844401 | chr4 | 3,449,652 | R509H | cSNP | 0.22 | 0.943 | 2.662 | 0.593 | 0.07 | 0.10 | 0.115 |
UNC93A
| 2235197 | chr6 | 167,709,702 | W151 | STOP GAINED | . | . | 4.525 | 1 | 0.1 | 0.15 | 0.163 |
ABCA13
| 1771229 | chr7 | 48,313,881 | F1540L | cSNP | . | 0.997 | 2.325 | 0.614 | 0.11 | 0.17 | 0.255 |
SSPO
| 1005603 | chr7 | 149,516,881 | S4028I | cSNP | . | . | . | . | 0.2 | 0.19 | 0.181 |
TTC40
| 12781609 | chr10 | 134,748,331 | S264N | cSNP | . | . | . | . | 0.37 | 0.36 | 0.412 |
Rare variant | ||||||||||||
DNAH17
| . | chr17 | 76,567,792 | I204M | cSNP | 0.11 | . | 1.926 | 0.992 | . | . | |
COL6A6
| 200963433 | chr3 | 130,289,976 | R906C | cSNP | 0 | 1 | 4.596 | 1 | 0.0014 | 0.01 | 0.017 |
Common variant | Functional prediction program | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene | RS# | Chr | POS | Amino acid change | Type | SIFT | Polyphen2 | PhyloP | PhastCons | Global | East Asian | Korean |
COL6A6
| 59021909 | chr3 | 130,285,929 | P556S | cSNP | 0.11 | 0.999 | 2.136 | 0.997 | 0.09 | 0.08 | 0.119 |
UVSSA
| 2276904 | chr4 | 1,349,029 | R391H | cSNP | . | . | . | . | 0.23 | 0.42 | 0.374 |
TUFT1
| 3828054 | chr1 | 151,512,895 | Q18R | cSNP | 0.77 | 0.688 | 1.688 | 0.763 | 0.1 | 0.03 | 0.047 |
TMEM175
| 34311866 | chr4 | 951,947 | M393T | cSNP | 0.01 | 0 | 1.299 | 0.563 | 0.12 | 0.12 | 0.155 |
EDN1
| 5370 | chr6 | 12,296,255 | K198N | cSNP | 0.08 | 0.454 | 0.049 | 0.895 | 0.21 | 0.28 | 0.258 |
NRAP
| 868738 | chr10 | 115,381,747 | R884C | cSNP | 0.01 | 0.986 | 4.833 | 1 | 0.24 | 0.17 | 0.198 |
Rare variant | ||||||||||||
CDX1
| 370852694 | chr5 | 149,546,819 | A127E | cSNP | 0.87 | 0.458 | 1.235 | 0.996 | . | . | 0.027 |
DNAH17
| 78098467 | chr17 | 76,510,974 | A1332V | cSNP | 0.6 | . | 4.052 | 1 | 0.01 | 0.04 | 0.037 |
ANKRD35
| 146839643 | chr1 | 145,560,094 | C194R | cSNP | 0.01 | 1 | 3.419 | 1 | 0.0037 | 0.01 | 0.016 |
Common variant | Functional prediction program | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene | #RS | Chr | POS | Amino acid change | Type | SIFT | Polyphen2 | PhyloP | PhastCons | Global | East Asian | Korean |
UVSSA
| 2276904 | chr4 | 1,349,029 | R391H | cSNP | . | . | . | . | 0.23 | 0.42 | 0.374 |
HGFAC
| 3748034 | chr4 | 3,446,091 | A218S | cSNP | 0.38 | 0.659 | 2 | 1 | 0.15 | 0.28 | 0.305 |
UNC93A
| 2235197 | chr6 | 167,709,702 | W151 | STOP GAINED | . | . | 4.525 | 1 | 0.1 | 0.15 | 0.163 |
ABCA13
| 17712299 | chr7 | 48,313,881 | F1540L | cSNP | . | 0.997 | 2.325 | 0.85 | 0.11 | 0.17 | 0.255 |
SSPO
| 1005603 | chr7 | 149,516,881 | S4028I | cSNP | . | . | . | 1 | 0.2 | 0.19 | 0.181 |
TTC40
| . | chr10 | 134,679,632 | T1596M | cSNP | . | . | . | . | . | . | |
Rare variant | ||||||||||||
COL6A6
| 200963433 | chr3 | 130,289,976 | R906C | cSNP | 0 | 1 | 4.596 | 1 | 0.0014 | 0.01 | 0.017 |
CDX1
| 370852694 | chr5 | 149,546,819 | A127E | cSNP | 0.87 | 0.458 | 1.235 | 0.996 | . | . | 0.027 |
SNP | Controls, n (%) | AD, n (%) | ||
---|---|---|---|---|
rs16830494 | Allele | G | 99 (81.1) | 189 (84.4) |
(c.5216G > A) | A | 23 (18.9) | 35 (15.6) | |
Genotype | GG | 39 (63.9) | 79 (71.2) | |
GA | 21 (34.4) | 29 (26.1) | ||
AA | 1 (1.6) | 3 (2.7) | ||
rs59021909 | Allele | C | 108 (88.5) | 199 (88.8) |
(c.1666C > T) | T | 14 (11.5) | 25 (11.2) | |
Genotype | CC | 47 (77.0) | 89 (79.5) | |
CT | 14 (23.0) | 21 (18.8) | ||
TT | 0 (0) | 2 (1.8) | ||
rs200963433 | Allele | C | 121 (99.2) | 220 (98.2) |
(c.2716C > T) | T | 1 (0.8) | 4 (1.8) | |
Genotype | CC | 60 (98.4) | 108 (96.4) | |
CT | 1 (1.6) | 4 (3.6) | ||
. | TT | 0 (0) | 0 (0) |
Gene | Chr | POS | Locus of AD-linkage |
---|---|---|---|
COL6A6
| 3 | 130.2–4 Mba
| 3q21 (chr3 122.2 Mb–129.5 Mb) [11] |
CDX1
| 5 | 149.5 Mb | 5q31-33 (Chr5 131.2 Mb–160.5 Mb) [29] |
ANKRD35
| 1 | 145.5 Mb | 1q21 (Chr1 143.2 Mb–155.1 Mb) [10] |
TUFT1
| 1 | 151.5 Mb | 1q21 (Chr1 143.2 Mb–155.1 Mb) |
FLG
| 1 | 152.2 Mb | 1q21 (Chr1 143.2 Mb–155.1 Mb) |