Table 1.
Characteristics of the most significant CNVs and overlapped genes from different genome-wide studies showing association with ALS
| Chr | Position start–end (CNV length) | CNV type | CNV detection method | ALS patients | Controls | Overlapped genes¥ | Reference |
|---|---|---|---|---|---|---|---|
| 1 | 41,119,815–41,147,030 | Gain | SNP array (TaqMan qPCR validation) |
8 (no. cases = 406) |
1 (no. controls = 404) |
None | [115] |
| 1 | Not reported (2246 bp) |
Deletion | SNP array | 3 (no. cases = 12) |
0 (no. controls = 24) |
Intron of FMN2 | [138] |
| 1 | 52,994,160–53,423,907 | Gain | BAC array (aCGH validation) |
1 (no. cases = 72) |
0 (no. controls = 700) |
ZYG11B, ECHDC2, SCP2, PODN, SCL1A7, CPT2, C1orf23, MAGOH | [165] |
| 3 | 2,944,819–2,947,844 | Gain | SNP array | 2 (no. cases = 32) |
0 (no. controls = 26 ) |
Intron of CNTN4 | [138, 165] |
| 3 | 89,485,137–89,499,861 | Loss | SNP array (TaqMan qPCR validation) |
2 (no. cases = 117) |
11 (no. controls = 109) |
EPHA3 | [96] |
| 3 | 33,270,957–33,296,620 | Gain | SNP array | 3 (no. cases = 575) |
18 (no. controls = 621) |
FBXL2 | [110, 111] |
| 3 | Not reported (6527 bp) |
Deletion | SNP array | 1 (no. cases = 12) |
0 (no. controls = 24) |
Promoter of CHL1 | [138] |
| 3 | Not reported (53,562 bp) |
Loss | SNP array | 1 (no. cases = 12) |
0 (no. controls = 24) |
52% of DHX30 (+ promoter), 9% of SMARCC1 (+ promoter) | [138] |
| 3 | 60,357,746–60,604,845 | Gain | BAC array (aCGH validation) |
1 (no. cases = 72) |
0 (no. controls = 700) |
FHIT | [165] |
| 4 | 761,587–1,014,752 | Gain | SNP array | 16 (no. cases = 575) |
4 (no. controls = 621) |
CPLX1, GAK, TMEM175, DGKQ, IDUA, SLC26A1, FGFRL1 | [110] |
| 4 | Not reported (144,772 bp) |
Loss | SNP array | 1 (no. cases = 12) |
0 (no. controls = 24) |
3% of RPS3A (+ promoter), 39% of LRBA (+ promoter) | [138] |
| 4 | Not reported (4546 bp) |
Deletion | SNP array | 1 (no. cases = 12) |
0 (no. controls = 24) |
Promoter of UGT8 | [138] |
| 5 | 28,842,013–28,912,873 | Gain | SNP array | 7 (no. cases = 575) |
0 (no. controls = 621) |
None | [110] |
| 5 | 45,850,032–46,384,240 | Gain | SNP array | 264 (no. cases = 575) |
174 (no. controls = 621) |
HCN1 (flanking) | [110] |
| 5 | 70,925,030–70,953,012 | Gain | MLPA assay | 121 (no. cases = 1689) |
68 (no. controls = 1780) |
SMN1–SMN2 | [45–47] |
| Loss | qPCR | 14 (no. cases = 167) |
4 (no. controls = 310) |
||||
| 6 | 109,034,609–109,074,882 | Gain | SNP array | 1 (no. cases = 32) |
0 (no. controls = 26 ) |
Intron of FOXO3 | [99] |
| 6 | 123,569,244–124,360,902 | Gain | BAC array (aCGH validation) |
1 (no. cases = 72) |
0 (no. controls = 700) |
TRDN, TCBA1 | [165] |
| 7 | 153,031,806–154,276,435 | Loss and gain | SNP array (TaqMan qPCR validation) |
10 (9 dup, 1 del) (no. cases = 1875) |
13 (12 dup, 1 del) (no. controls = 8731) |
DPP6 | [84] |
| 7 | 61,663,407–62,155,064 | Gain | SNP array | 177 (no. cases = 575) |
132 (no. controls = 621) |
None | [110] |
| 8 | 47,062,007–47,406,312 | Gain | SNP array | 30 (no. cases = 575) |
8 (no. controls = 621) |
POTEA (flanking) | [110] |
| 8 | 47,062,007–47,711,911 | Gain | SNP array | 3 (no. cases = 575) |
18 (no. controls = 621) |
None | [110] |
| 8 | 43,689,385–43,910,848 | Gain | SNP array | 74 (no. cases = 575) |
52 (no. controls = 621) |
None | [110] |
| 8 | 73,609,541–73,629,084 | Gain | SNP array | 1 (no. cases = 32) |
0 (no. controls = 26 ) |
Region overlaps with 86.50% of KCNB2 | [99] |
| 8 | 144,686,338–144,765,210 | Loss and gain | SNP array | 6 (no. cases = 575) |
0 (no. controls = 621) |
ZC3H3, GSDM, C8orf73, NAPRT1, EEF1D, TIGD5, PYCRL | [110] |
| 10 | 1,050,000–1,090,000 | Gain | aCGH (TaqMan qPCR and high-density customized aCGH validation) |
46 (no. cases = 83) |
10 (no. controls = 100) |
IDI1-IDI2 | [78] |
| 11 | 50,545,00–50,586,426 | Loss | SNP array | 21 (no. cases = 117) |
2 (no. controls = 109) |
None | [96] |
| 11 | 539,119–652,407 | Loss | SNP array | 5 (no. cases = 575) |
0 (no. controls = 621) |
OR4A5, OR4C12 (flanking) LRRC56, C11orf35, RASSF7, PHRF1, IRF7, MUPCDH, SCT, DRD4, DEAF1 | [110] |
| 12 | 36,528,296–36,801,139 | Gain | SNP array | 157 (no. cases = 575) |
8 (no. controls = 621) |
None | [110] |
| 14 | 103,232,016–103,721,150 | Gain | SNP array | 5 (no. cases = 575) |
0 (no. controls = 621) |
KLC1, XRCC3, ZFYVE21, PPP1R13B, C14orf2, TDRD9, ASPG, KIF26A | [110] |
| 14 | Not reported (4384 bp) |
Deletion | SNP array | 5 (no. cases = 12) |
0 (no. controls = 24) |
None | [138] |
| 15 | 20,387,566–44,672,396 | Loss and gain | SNP array (TaqMan qPCR validation) |
12 (4 dup, 8 del) (no. cases = 1875) |
34 (31 dup, 3 del) (no. controls = 8731) |
TUBGCP5, CYFIP1, NIPA2, NIPA1 | [84] |
| 15 | Not reported (5695 bp) |
Deletion | SNP array | 2 (no. cases = 12) |
0 (no. controls = 24) |
None | [138] |
| 15 | 19,818,989–20,084,080 | Deletion | SNP array | 2 (no. cases = 32) |
0 (no. controls = 26 ) |
LOC650137 (+), OR4M2 (+), OR4N4 (+) | [99] |
| 16 | 76,578,045–77,657,555 | Loss | SNP array | 0 (no. cases = 406) |
6 (no. controls = 404) |
CLEC3A, WWOX | [115] |
| 16 | 87,957,353–87,971,263 | Gain | SNP array | 2 (no. cases = 32) |
0 (no. controls = 26) |
Intron of ANKRD11 | [99] |
| 16 | 969,913–1,834,962 | Gain | SNP array | 8 (no. cases = 575) |
15 (no. controls = 621) |
SOX8, SSTR5, C1QTNF8, CACNA1H, TPSG1, TPSB2, TPSAB1, TPSD1, UBE2I, BAIAP3, C16orf42, GNPTG, UNKL, C16orf91, CLCN7, C16orf38, TELO2, IFT140, TMEM204, CRAMP1L, HN1L, MAPK8IP3, NME3, MRPS34, EME2, SPSB3, NUBP2, IGFALS, HAGH, FAHD1, C16orf73 | [110] |
| 17 | Not reported (1159 bp) | Gain | SNP array | 1 (no. cases = 12) |
0 (no. controls = 24) |
AATK, ACTG1, AZI1, BAHCC1, BAIAP2, C17orf55, C17orf56, C17orf70, C17orf89, CHMP6, FSCN2, SLC38A10, TMEM105, 2% of NPLOC4 (+ promoter), 31% of KIAA1303 | [138] |
| 19 | 20,860,930–20,875,787 | Loss | SNP array | 15 (no. cases = 117) |
2 (no. controls = 109) |
None | [96] |
| 19 | 32,615,675-32,935,836 | Gain | SNP array | 165 (no. cases = 575) |
122 (no. controls = 621) |
RDH13 | [110] |
| 19 | Not reported | Loss | SNP array | 2 (no. cases = 12) |
0 (no. controls = 24) |
Intron of ZFP14 | [138] |
| 22 | 23,696,411–24,240,667 | Loss and gain | SNP array | 10 (8 gain 2 loss) (no. cases = 406) |
28 (no. controls = 404) |
CRYBB3, CRYBB2, LOC91353, LRP5L, CRYBB2P1 | [115] |
| 22 | 21,011,312–21,394,287 | Loss | SNP array | 0 (no. cases = 575) |
11 (no. controls = 621) |
ZNF280B, ZNF280A, PRAME, BCR, GGTLC2 | [110, 138] |
| 22 | 29,489,697–29,489,738 | Deletion | SSCP | 5 (no. cases = 530) |
2 (no. controls = 379) |
NEFH | [68] |
| X | 139,400,576–telomere | Deletion | BAC array (aCGH validation) |
1 (no. cases = 72) |
0 (no. controls = 700) |
>100 (No ALS candidate genes) | [165] |
| X | 139,526,743–139,942,807 | Gain | BAC array (aCGH validation) |
1 (no. cases = 72) |
0 (no. controls = 700) |
CDR1 | [165] |
The table shows the most significant CNV loci and relative genes that partially or completely fall within them. Chromosomal positions are referred to the human reference genome assembly corresponding to each individual study: in particular [115], [40], and [81] refer to the NCBI reference sequence build 36, [98] refers to the build 38 and [41] refers to UCSC Genome Browser, May 2004 Freeze. In the case of [71], the authors described deletion coordinates by using the numbering of the published sequence by Lees et al. EMBO J. 1988. Genes that may be reasonable ALS candidates are in bold
Chr Chromosome, SSCP single-strand conformation polymorphism analysis, Loss heterozygous deletion, Deletion homozygous deletion
¥Gene symbols correspond to the NCBI Refseq names