Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Methods
3. Results
3.1. Clinical Assessment and Dioxin Level in the Father’s Serum
3.2. Whole Genome Sequencing and Identification of Variants
3.3. De Novo Variants
3.4. Analysis of Germline Variations under Recessive Model
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Congener | TEQ (ppt) |
---|---|
Sample amount (g) | 15.236 |
lipid content (%) | 0.177 |
Sample weight (lipid) (g) | 0.027 |
Values in pg/g (ppt), lipid based | |
2.3.7.8-Tetra-CDD (TCDD) | 87 |
1.2.3.7.8-Penta-CDD (PeCDD) | 12 |
1.2.3.4.7.8-Hexa-CDD | 9.0 |
1.2.3.6.7.8-Hexa-CDD | 33 |
1.2.3.7.8.9-Hexa-CDD | 8.2 |
1.2.3.4.6.7.8-Hepta-CDD | 35 |
OCDD | 385 |
2.3.7.8-Tetra-CDF | 3.2 |
1.2.3.7.8-Penta-CDF | 2.8 |
2.3.4.7.8-Penta-CDF | 9.6 |
1.2.3.4.7.8-Hexa-CDF | 27 |
1.2.3.6.7.8-Hexa-CDF | 15 |
1.2.3.7.8.9-Hexa-CDF | n.d. (3) |
2.3.4.6.7.8-Hexa-CDF | 8.4 |
1.2.3.4.6.7.8-Hepta-CDF | 18 |
1.2.3.4.7.8.9-Hepta-CDF | n.d. (4) |
OCDF | n.d. (13) |
3,3’,4,4’-TCB (77) | n.d. (690) |
3,4,4’,5-TCB (81) | n.d. (29) |
3,3’,4,4’,5-PeCB (126) | 123 |
3,3’,4,4’,5,5’-HxCB (169) | 61 |
2,3,3’,4,4’-PeCB (105) | 5005 |
2,3,4,4’,5-PeCB (114) | 742 |
2,3’,4,4’,5-PeCB (118) | 22,592 |
2’,3,4,4’,5-PeCB (123) | 244 |
2,3,3’,4,4’,5-HxCB (156) | 5873 |
2,3,3’,4,4’,5’-HxCB (157) | 1579 |
2,3’,4,4’,5,5’-HxCB (167) | 2883 |
2,3,3’,4,4’,5,5’-HpCB (189) | 938 |
Total PCDDs/PCDFs | 654 |
TEQ (World Health Organization, WHO) based on PCDD/F | 115 |
Type | Father | Mother | Proband | |
---|---|---|---|---|
WGS deep coverage (x) | 32.2 | 31.8 | 31.5 | |
SNV | 1,461,494 | 1,419,542 | 1,388,686 | |
Shared with dbSNP v138 | 1,438,017 | 1,396,439 | 1,366,410 | |
Shared with 1000G | 6619 | 6963 | 6526 | |
Novel variants | 16,858 | 16,140 | 15,750 | |
Intronic | 13,555 | 13,068 | 12,751 | |
Exonic | 243 | 239 | 204 | |
5’UTR | 54 | 46 | 38 | |
3’UTR | 309 | 289 | 259 | |
ncRNA_intronic | 2551 | 2355 | 2379 | |
ncRNA_exonic | 145 | 140 | 117 | |
Splicing site | 1 | 3 | 2 | |
Indel | 185,588 | 180,389 | 174,440 | |
Shared with dbSNP v138 | 91,552 | 89,948 | 87,532 | |
Shared with 1000G | 5048 | 4942 | 4560 | |
Novel variants | 88,988 | 85,499 | 82,348 | |
Intronic | 73,626 | 70,493 | 67,997 | |
Exonic | 63 | 56 | 45 | |
5’UTR | 129 | 114 | 109 | |
3’UTR | 1850 | 1807 | 1690 | |
ncRNA_intronic | 12,750 | 12,495 | 12,000 | |
ncRNA_exonic | 502 | 479 | 448 | |
Splicing site | 68 | 55 | 59 | |
Total (SNV + Indel) | 1,647,082 | 1,599,931 | 1,563,126 |
Type of Variant | Chromosomal Position | Transcript Level Position | Gene | Ref | Variant | AA Change | Provean Prediction | SIFT Prediction | Polyphen-2 Prediction | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Prediction | Score | Prediction | Score | Prediction | Score | |||||||
de novo | NC_000021.8:g.40182013 | NM_001256295.1:c.47 | ETS2 | CC | CT | T22I | Not detected | Not detected | Not detected | Not detected | benign | 0.055 |
de novo | NC_000019.9:g.52826007 | NM_144684.2:c.1504 | ZNF480 | CC | CT | R502W | Deleterious | −2.74 | Tolerated | 0.237 | probably damaging | 0.999 |
compound heterozygosity | NC_000001.10:g.214814052 | NM_016343.3:c.2371 | CENPF | CC | CG | P791A | Neutral | −0.24 | Tolerated | 0.597 | benign | 0.001 |
compound heterozygosity | NC_000001.10:g.214815601 | NM_016343.3:c.3920 | CENPF | GG | GA | C1307Y | Deleterious | −4.22 | Tolerated | 0.087 | probably damaging | 1 |
compound heterozygosity | NC_000002.11:g.179514619 | XM_005246830.1:c.907 | TTN | GG | AG | P13274S | Deleterious | −3.53 | Tolerated | 0.354 | benign | 0.006 |
compound heterozygosity | NC_000002.11:g.179578790 | NM_005246830.1:c.25647 | TTN | CC | CG | K8865N | Deleterious | −3.35 | Tolerated | 0.091 | probably damaging | 0.978 |
homozygous deletion | NC_000001.10:g. 149040000_149195000del | NBPF25P | NC_000001.10:g. 149040000_149195000del (150 kb deletion) | |||||||||
homozygous deletion | NC_000012.11:g.10580000_10590000del | KLRC1, KLRC2 | NC_000012.11:g.10580000_10590000del (10 kb deletion) |
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Nguyen, D.T.; Nguyen, H.H.; Nguyen, T.D.; Nguyen, T.T.H.; Nakano, K.; Maejima, K.; Sasaki-Oku, A.; Nguyen, V.B.; Nguyen, D.B.; Le, B.Q.; et al. Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability. Int. J. Environ. Res. Public Health 2018, 15, 2629. https://doi.org/10.3390/ijerph15122629
Nguyen DT, Nguyen HH, Nguyen TD, Nguyen TTH, Nakano K, Maejima K, Sasaki-Oku A, Nguyen VB, Nguyen DB, Le BQ, et al. Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability. International Journal of Environmental Research and Public Health. 2018; 15(12):2629. https://doi.org/10.3390/ijerph15122629
Chicago/Turabian StyleNguyen, Dang Ton, Hai Ha Nguyen, Thuy Duong Nguyen, Thi Thanh Hoa Nguyen, Kaoru Nakano, Kazuhiro Maejima, Aya Sasaki-Oku, Van Ba Nguyen, Duy Bac Nguyen, Bach Quang Le, and et al. 2018. "Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability" International Journal of Environmental Research and Public Health 15, no. 12: 2629. https://doi.org/10.3390/ijerph15122629