Table 1. Summary of copy number variations detected in 157 samples of patients with severe obesity.
Control frequency refers to the frequency of the same type of rearrangement, deletion or duplication, in the control cohort (9,820 subjects). Progenitor phenotype refers only to the progenitor carrying the alteration. Hg19 assembly. F: female; M: male; Mat: maternal; Pat: paternal; N: normal; OW: overweight; OB: obesity; NA: not available; +: description of a mouse model with a phenotype related to body mass index (S1 Table). The genes interrupted at any of the breakpoints of the CNV are shown in boldface.
| Case | Gender | Gain/ Loss | Region | Length (kb) | Hg19 coordinates | Genes | Inheritance | Progenitor phenotype | Control frequency | Mouse model |
|---|---|---|---|---|---|---|---|---|---|---|
| Recurrent alterations in obese patients | ||||||||||
| Ob_1 | F | Gain | 9q34.3 | 149 | chr9:138149166–138298164 | C9orf62 | Mat | N | 1 | |
| Ob_2 | F | Gain | 9q34.3 | 139 | chr9:138149166–138288052 | C9orf62 | Pat | OW | 1 | |
| Ob_3 | F | Gain | 9q34.3 | 139 | chr9:138149166–138288052 | C9orf62 | Mat | OW | 1 | |
| Ob_4 | M | Gain | 7p22.1 | 106 | chr7:5785086–5891221 | RNF216,ZNF815 | Mat | OB | 4 | |
| Ob_5 | F | Gain | 7p22.1 | 106 | chr7:5785086–5891221 | RNF216,ZNF815 | Pat | OB | 4 | |
| Ob_6 | F | Loss | 11p15.4 | 104 | chr11:4583029–4687238 | TRIM68 and 5 more genes | Pat | OB | 2 | |
| Obese specific alterations, not found in 10,320 controls, co-segregating with the phenotype in the family | ||||||||||
| Ob_7 | F | Gain | 3q29 | 1169 | chr3:196533320–197701913 | DLG1,PAK2,LMLN and 10 more genes | Mat | OB | 0 | + |
| Ob_8 | F | Gain | 4q12 | 361 | chr4:53842714–54203701 | SCFD2 | Pat | OB | 0 | |
| Ob_9 | F | Loss | 6q23.2 | 166 | chr6:133386327–133552737 | LINC00326 | Mat | OB | 0 | |
| Ob_10 | M | Loss | 5q21.1 | 157 | chr5:101620174–101776835 | SLCO4C1,SLCO6A1 | Pat | OB | 0 | |
| Ob_11 | M | Gain | 7p15.3 | 202 | chr7:21858215–22059791 | CDCA7L,DNAH11 | Pat | OB | 0 | |
| Ob_12 | M | Gain | 7p15.3 | 137 | chr7:24258773–24395900 | NPY | Mat | OB | 0 | + |
| Ob_13 | F | Gain | 10p14 | 1029 | chr10:10743956–11773389 | CELF2 and 4 more genes | Mat | OB | 0 | |
| Ob_14 | M | Gain | 14q31.1 | 105 | chr14:81204951–81309536 | CEP128 | Mat | OB | 0 | |
| Ob_15 | F | Gain | 14q31.3 | 274 | chr14:89171711–89445350 | EML5,TTC8 | Mat | OB | 0 | + |
| Ob_16 | M | Gain | 19p13.3 | 428 | chr19:2221792–2650034 | AMH,DOT1L,GNG7 and 14 more genes | Pat | OB | 0 | |
| Ob_17 | M | Gain | 20p12.1 | 220 | chr20:13255679–13476090 | ISM1,TASP1 | Pat | OB | 0 | + |
| Copy number variations detected in single cases | ||||||||||
| Ob_18 | F | Gain | 1p36.13 | 223 | chr1:17202355–17425829 | ATP13A2,PADI2 and 3 more genes | Mat | N | 0 | |
| Ob_19 | M | Gain | 1p31.3 | 405 | chr1:61704166–62109502 | NFIA | Mat | OW | 3 | |
| Ob_20 | M | Gain | 2q24.1 | 336 | chr2:159176303–159512667 | CCDC148,PKP4 | Mat | N | 0 | |
| Ob_21 | M | Gain | 3p26.1 | 214 | chr3:4272253–4486303 | SETMAR,SUMF1 | Pat | N | 2 | |
| Ob_22 | M | Gain | 3p26.1 | 364 | chr3:7660133–8024019 | GRM7 | Mat | OW | 3 | |
| Ob_15 | F | Loss | 3q12.3 | 3590 | chr3:101816344–105406145 | ZPLD1, ALCAM, CBLB | De novo | - | 0 | |
| Ob_23 | M | Gain | 4q13.3 | 101 | chr4:71055318–71156301 | C4orf7,CSN3,ODAM | Mat | N | 0 | |
| Ob_18 | F | Gain | 5p15.33 | 295 | chr5:303686–598237 | AHRR,PDCD6, and 6 more | Mat | OW | 3 | |
| Ob_24 | M | Gain | 5q35.3 | 397 | chr5:179220638–179617799 | C5orf45,RASGEF1C and 6 more | Pat | N | 0 | |
| Ob_25 | M | Gain | 6q15 | 445 | chr6:89349438–89793993 | PNRC1,RNGTT | Mat | OW | 0 | |
| Ob_26 | F | Gain | 7p14.1 | 105 | chr7:40117098–40221714 | C7orf10,C7orf11,CDK13 | Pat | OB | 1 | |
| Ob_27 | F | Gain | 9p24.3 | 448 | chr9:396232–844001 | DMRT1,DOCK8,KANK1 | Mat | N | 2 | |
| Ob_15 | F | Loss | 10q21.3 | 156 | chr10:69418270–69574169 | CTNNA3,DNAJC12 | Mat | OB | 1 | |
| Ob_28 | M | Gain | 11p13 | 129 | chr11:32986850–33116054 | CSTF3,QSER1 and 3 more genes | Pat | N | 0 | |
| Ob_29 | F | Gain | 12q23.3 | 116 | chr12:104476277–104591886 | HCFC2,NFYB | Pat | NA | 0 | |
| Ob_30 | M | Gain | 12q24.33 | 218 | chr12:131620578–131838842 | GPR133,LOC116437 | Pat | OB | 1 | |
| Ob_16 | M | Gain | 15q25.2 | 418 | chr15:84414592–84832932 | ADAMTSL3,EFTUD1P1 | Pat | OB | 1 | |
| Ob_31 | M | Gain | 17q23.1 | 248 | chr17:58113570–58361461 | CA4,USP32 and 5 more genes | NA | NA | 0 | |
| Ob_32 | F | Gain | 18p11.31 | 245 | chr18:6308208–6553040 | L3MBTL4,LOC100130480,MIR4317 | Mat | OW | 0 | |
| Ob_5 | F | Gain | 18p11.21 | 262 | chr18:12917703–13180058 | CEP192,SEH1L | Mat | N | 2 | |
| Ob_14 | M | Gain | 20p12.1 | 204 | chr20:13867165–14070869 | MACROD2,SEL1L2 | Pat | N | 0 | |
| Ob_33 | F | Gain | 21q21.3 | 163 | chr21:31280603–31443375 | GRIK1 | Pat | OB | 1 | + |
| Ob_34 | F | Loss | 22q11.22 | 261 | chr22:22312292–22573637 | TOP3B | Pat | OB | 2 | |
| Ob_35 | F | Loss | 22q11.22 | 676 | chr22:22981587–23657613 | BCR and 7 more | Mat | NA | 0 | |
| Ob_36 | M | Gain | 22q13.33 | 198 | chr22:50342728–50584201 | IL17REL,MLC1,MOV10L1,PIM3 | Pat | NA | 0 | |
| Copy number variations detected in X chromosome | ||||||||||
| Ob_37 | F | Gain | Xp22.2 | 305 | chrX:15952591–16257827 | GRPR | Mat | N | 1 | + |
| Ob_6 | F | Gain | Xq26.2 | 369 | chrX:130639755–131008470 | LOC286467,OR13H1,IGSF1 | Pat | OB | 0 | |