Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Animals, Irradiation and DNA Isolation
4.2. Array CGH
4.3. Quantitative PCR (qPCR)
4.4. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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F1 Mouse | No. of Positive Probes | Size (bp) | Chromosomal Location (GRCm38) | qPCR Probe Location (GRCm38) | Involved Genes | ||||
---|---|---|---|---|---|---|---|---|---|
ID | Sex | 1st Array CGH | 2nd Array CGH | ||||||
Non-Irradiated | Deletion | 0mGyX3 | M | 11 | >50 | 1,103,254 | Chr13:66,699,838–67,803,092 | 66,700,397 | Gm40988, Gm48404, Gm40989, Gm7896, Gm48413, Gm40989, Vmn2r-ps108, Gm48412, Gm48414, Gm10323, Vmn2r-ps109, Cbx3-ps4, Gm5451, Gm7911, Uqcrb, Gm10767, Mterf3, Ptdss1, 4933433G19Rik, Zfp712, Gm48705, Gm46440, Zfp708, Gm28557, Gm17938, Rslcan18, Zfp759, Gm48732, Gm48733, Rsl1, Gm49646, Gm9626, Zfp455, Gm49064, Zfp458, F630042J09Rik, Zfp457, Gm48824, Zfp595, Gm28044, Zfp593, Zfp456, Gm17039, Zfp953, Gm28041, Zfp429, Gm48900, Zfp459, Zfp874a, Gm38307, Gm7928, Zfp874b, Zfp58, Gm26965, Zfp87, Zfp748, 9430065F17Rik, Zfp729b, Gm49345, Zfp729a, Zfp738, Gm48095, Gm26875, Zfp65, Gm48894, Zfp85, Gm9894, Zfp493, 4930525G20Rik |
0mGyH5 a | M | 7 | >50 | 666,200 | Chr2:177,329,278–177,995,478 | 178,041,392 | Gm14414, Zfp970, Gm14403, Gm14324, Gm14322, Gm14326, Gm14327, Rps8-ps5 | ||
0mGyH5 a | M | 22 | >50 | 146,136 | Chr12:40,469,827–40,615,963 | 40,596,701 | Dock4 | ||
0mGyG2 | M | 19 | >50 | 74,519 | Chr1:112,845,241–112,919,760 | 112,877,741 | Gm8204 | ||
0mGyS6 | F | 14 | >50 | 56,272 | Chr7:102,192,468–102,248,740 | 102,193,027 | Nup98, Pgap2, Rhog | ||
0mGyK4 | F | 9 | >50 | 34,160 | Chr3:5,533,449–5,567,609 | 5,560,033 | Pex2 | ||
0mGyK5 | F | 10 | >50 | 25,412 | Chr13:54,919,455–54,944,867 | 54,942,291 | 4930526F13Rik | ||
0mGyJ3 | F | 6 | >50 | 17,346 | Chr4:128,415,985–128,433,331 | 128,416,544 | Csmd2 | ||
0mGyV2 | M | 1 | 2 | 461 | Chr2:126,675,275–126,675,736 | 126,675,329 | Gabpb1 | ||
0mGyA3 | F | 1 | 2 | 212 | Chr4:34,844,952–34,845,164 | 34,845,005 | Zfp292 | ||
0mGyO7 | F | 1 | 2 | 153 | Chr1:7,323,388–7,323,541 | 7,323,321 | |||
Duplication | 0mGyZ1 | M | 158 | >50 | 1,100,262 | Chr6:79,988,064–81,088,326 | 79,988,623 | Lrrtm4, Gm43900 | |
0mGyE4 | F | 1 | 13 | 1535 | Chr8:123,427,701–123,429,236 | 123,429,010 | Galnt2, Def8 | ||
0mGyG5 | F | 1 | 3 | 412 | Chr9:49,721,288–49,721,700 | 49,721,288 | Ncam1 | ||
Irradiated | Deletion | 20mGyL5 | M | 575 | >50 | 1,908,155 | Chr13:63,399,812–65,307,967 | 65,307,023 | Fancc, patch1, A930032L01 Rik, Gm30655, Gm30709, 1700024I08 Rik, Gm47387, Gm47390, Gm47417, Gm47418, Ercc6l2, Gm7695, Hsd17b3, Slc35d2, Zfp367, Gm47513, Habp4, Cdc14b, Gm46424, 1810034E14 Rik, Gm47004,Gm47003, Gm25654, Prxl2c, Zfp182, Gm47123, Gm49230, Ctsl, 1700015C15 Rik, Cdk20, Gm31218, Fam240b, Gm7712, Gm47190, Gm4810, Gm47191, Gm47193, Gm5791, Gm4935, Gm47194, Gm7065, Cntnap3, Spata31, Eif1-ps2, Prss47, Mfsd14b, Spata31d1c, Gm6888, Gm3785, Olfr465-ps1, Olfr466, Gm24130, Nlrp4f, Gm47249, Gm36445, Gm47250, Gm47251, Gm47254, Gm10775, Zfp369, Gm47258 |
20mGyI5 | F | 200 | >50 | 742,233 | Chr10:99,214,798–99,957,031 | 99,959,613 | Gm34777, Gm34574, Gm48884, Dusp6, Gm48089, B530045E10 Rik, Gm34921, Gad1, Gm34983, Gm35035, Gm48085, Gm20110, Gm18409, Gm35101, Gm47578, Csl, Gm47579 | ||
20mGyL8 | F | 145 | >50 | 353,159 | Chr3:105,510,798–105,863,957 | 105,511,357 | AK018929, Kcnd3 | ||
20mGyE1 | M | 83 | >50 | 235,104 | Chr9:57,625,823–57,860,927 | 57,854,366 | Csk, Cyp1a2, Cyp1a1, Edc3, Clk3, Gm17231, Arid3b | ||
20mGyL2 | M | 36 | >50 | 145,401 | Chr14:37,914,599–38,060,000 | 37,936,448 | Gm47974 | ||
20mGyA1 | M | 12 | >50 | 133,572 | Chr9:114,085,760–114,219,332 | 114,213,599 | |||
20mGyAA4 a | F | 34 | >50 | 102,921 | Chr1:117,376,753–117,479,674 | 117,377,055 | |||
20mGyU6 | F | 35 | >50 | 76,287 | Chr1:172,286,528–172,362,815 | 172,287,087 | Igsf8, Atp1a2, Kcnj9, Gm36937, Kcnj10 | ||
20mGyV6 | F | 29 | >50 | 75,893 | Chr2:45,606,923–45,682,816 | 45,607,482 | |||
20mGyW1 | M | 14 | >50 | 40,175 | Chr19:54,228,002–54,268,177 | 54,228,561 | |||
20mGyL4 | M | 8 | >50 | 32,881 | Chr6:138,709,973–138,742,854 | 138,741,398 | |||
20mGyU8 | F | 7 | >50 | 29,202 | Chr9:100,793,927–100,823,129 | 100,794,486 | Stag1 | ||
20mGyX1 | M | 12 | >50 | 28,507 | Chr12:92,023,170–92,051,677 | 92,047,867 | |||
20mGyV1 | M | 8 | >50 | 22,299 | Chr11:111,762,690–111,784,989 | 111,763,249 | |||
20mGyN4 a | M | 6 | 32 | 10,224 | Chr6:34,932,670–34,942,894 | 34,941,090 | Stra8 | ||
20mGyV4 | F | 4 | >50 | 9424 | Chr10:107,833,661–107843085 | 107,834,220 | Otogl | ||
20mGyX2 | F | 3 | 40 | 5965 | Chr14:112,914,840–112,920,805 | 112,919,755 | |||
20mGyAA4a | F | 2 | 33 | 4495 | Chr17:81,065,337–81,069,832 | 81,069,694 | |||
20mGyU5 | M | 2 | 23 | 3469 | Chr11:92,816,645–92,820,114 | 92,817,204 | |||
20mGyY1 a | M | 2 | 16 | 3370 | Chr11:105,950,869–105,954,239 | 105,951,424 | |||
20mGyG2 | M | 2 | 16 | 3286 | Chr14:40,993,918–40,997,204 | 40,996,166 | Prxl2a | ||
20mGyN4 a | M | 1 | 19 | 2367 | Chr4:50,541,636–50,544,003 | 50,543,175 | |||
20mGyG7 | F | 1 | 17 | 1878 | Chr4:90,232,441–90,234,319 | 90,234,260 | |||
20mGyB5 | F | 1 | 3 | 1040 | Chr10:69,420,081–69,421,121 | 69,420,140 | Ank3-246 | ||
20mGyG5 | F | 1 | 9 | 948 | Chr1:44,804,456–44,805,404 | 44,804,512 | |||
20mGyX7 | F | 1 | 5 | 732 | Chr4:21,163,257–21,163,989 | 21,163,816 | |||
20mGyH3 | M | 1 | 8 | 716 | Chr3:119,702,208–119,702,924 | 119,702,263 | |||
20mGyY1 a | M | 1 | 4 | 356 | Chr18:27,125,326–27,125,682 | 27,125,885 | |||
20mGyX5 | F | 1 | 2 | 191 | Chr12:81,490,882–81,491,073 | 81,491,441 | Synj2bp | ||
20mGyB2 | F | 1 | 2 | 156 | Chr17:4,507,025–4,507,181 | 4,507,139 | |||
Duplication | 20mGyE5 | F | 86 | >50 | 305,969 | Chr6:48,055,971–48,361,940 | 48,360,175 | Zfp746, Gm16630 |
No. of Positive Probes in 1st Array CGH | ≥2 (Type L) | 1 (Type S) | (Total) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No. of Positive Probes in 2nd Array CGH | ≥5 | 4 | 3 | 2 | (Total) | ||||||||||
Deletion (del) or Duplication (dup) | Del | Dup | Del | Dup | Del | Dup | Del | Dup | Del | Dup | Del | Dup | Del | Dup | |
Non-irradiated (n = 156) | Detected by array CGH | 8 | 1 | 0 | 1 | 1 | 0 | 0 | 2 | 13 | 4 | 14 | 7 | 22 | 8 |
Confirmed by qPCR | 8 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 3 | 0 | 3 | 2 | 11 | 3 | |
Irradiated (n = 142) | Detected by array CGH | 22 | 1 | 5 | 0 | 2 | 0 | 2 | 0 | 3 | 0 | 12 | 0 | 34 | 1 |
Confirmed by qPCR | 22 | 1 | 5 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 9 | 0 | 31 | 1 |
No. of Positive Probes in 1st Array CGH | ≥2 (Type L) | 1 (Type S) | (Total) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No. of Positive Probes in 2nd Array CGH | ≥5 | 4 | 3 | 2 | (Total) | |||||||||||
Deletion (Del) or Duplication (Dup) | Del | Dup | Del | Dup | Del | Dup | Del | Dup | Del | Dup | Del | Dup | Del | Dup | ||
Non-irradiated | 0mGyJ4 (F) | Detected by array CGH | 0 | 0 | 0 | 0 | 1 | 0 | 5 | 0 | 13 | 0 | 19 | 0 | 19 | 0 |
Analyzed by qPCR | 0 | 0 | 0 | 0 | 1 | 0 | 5 | 0 | 1 | 0 | 7 | 0 | 7 | 0 | ||
Confirmed by qPCR | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 4 | 0 | 4 | 0 | ||
0mGyX5 (F) | Detected by array CGH | 0 | 0 | 0 | 0 | 3 | 0 | 9 | 0 | 43 | 0 | 55 | 0 | 55 | 0 | |
Analyzed by qPCR | 0 | 0 | 0 | 0 | 3 | 0 | 2 | 0 | 5 | 0 | 10 | 0 | 10 | 0 | ||
Confirmed by qPCR | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 5 | 0 | 5 | 0 | ||
Irradiated | 20mGyA2 (M) | Detected by array CGH | 0 | 0 | 14 | 0 | 18 | 0 | 27 | 0 | 49 | 0 | 108 | 0 | 108 | 0 |
Analyzed by qPCR | 0 | 0 | 3 | 0 | 3 | 0 | 5 | 0 | 11 | 0 | 22 | 0 | 22 | 0 | ||
Confirmed by qPCR | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 6 | 0 | 11 | 0 | 11 | 0 | ||
20mGyF5 (F) | Detected by array CGH | 0 | 0 | 1 | 0 | 2 | 0 | 3 | 0 | 10 | 0 | 16 | 0 | 16 | 0 | |
Analyzed by qPCR | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 10 | 0 | 13 | 0 | 13 | 0 | ||
Confirmed by qPCR | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 5 | 0 | 5 | 0 | ||
20mGyL1 (M) | Detected by array CGH | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 6 | 0 | 9 | 0 | 9 | 0 | |
Analyzed by qPCR | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 6 | 0 | 8 | 0 | 8 | 0 | ||
Confirmed by qPCR | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 4 | 0 | 4 | 0 |
No. of Positive Probes in 1st Array CGH | ≥2 (Type L) | 1 (Type S) | (Total) | |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Deletion (Del) or Duplication (Dup) | Del | Dup | Del | Dup | Del | Dup | ||||||||||||||
Sex | n | n | % | pa | n | % | pa | n | % | pa | n | % | pa | n | % | pa | n | % | pa | |
M | Non-irradiated | 75 | 4 | 5.3 | 0.018 | 1 | 1.3 | >0.1 | 1 | 1.3 | >0.1 | 0 | 0.0 | ND b | 5 | 6.6 | 0.024 | 1 | 1.3 | >0.1 |
Irradiated | 75 | 13 | 17.3 | 0 | 0.0 | 3 | 4.0 | 0 | 0.0 | 14 c | 18.7 | 0 | 0.0 | |||||||
F | Non-irradiated | 81 | 4 | 4.9 | >0.1 | 0 | 0.0 | >0.1 | 2 | 2.5 | 0.085 | 2 | 2.4 | >0.1 | 6 | 7.4 | 0.009 | 2 | 2.4 | >0.1 |
Irradiated | 67 | 9 | 13.4 | 1 | 1.4 | 6 | 9.0 | 0 | 0.0 | 15 | 22.4 | 1 | 1.4 | |||||||
Total | Non-irradiated | 156 | 8 | 5.1 | 0.004 | 1 | 0.6 | >0.1 | 3 | 1.9 | 0.075 | 2 | 1.2 | >0.1 | 11 | 7.1 | 0.001 | 3 | 1.9 | >0.1 |
Irradiated | 142 | 22 | 15.5 | 1 | 0.7 | 9 | 6.3 | 0 | 0.0 | 29 | 20.4 | 1 | 0.7 |
No. of Deletions | Deletion Size (bp) | |||
---|---|---|---|---|
GM a | GSD b | |||
Non-irradiated | 11 | 18,762 | 12.181 | p = 0.6758 c |
Irradiated | 31 | 12,674 | 21.484 |
Group of F1 Mice | No. of F1 Mice | Life Span (Days) | ||||
---|---|---|---|---|---|---|
(Mean ± SD) | ||||||
M | Non-irradiated | CNV− b | 70 | 914 | ± | 170 |
CNV+ c | 4 | 859 | ± | 161 | ||
Irradiated | CNV- | 56 | 824 | ± | 163 | |
CNV+ | 16 | 881 | ± | 155 | ||
F | Non-irradiated | CNV- | 72 | 813 | ± | 132 |
CNV+ | 8 | 772 | ± | 124 | ||
Irradiated | CNV- | 54 | 833 | ± | 140 | |
CNV+ | 10 | 738 | ± | 125 |
Factor | Hazard Ratio | Z Value | p Value |
---|---|---|---|
Sex a | 0.507 | −5.40 | <0.0001 |
Irradiation a | 0.851 | −1.32 | 0.187 |
CNVs a | 0.697 | −2.00 | 0.045 |
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Ogura, K.; Ayabe, Y.; Harada, C.; Tanaka, I.B., III; Tanaka, S.; Komura, J.-i. Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation. Int. J. Mol. Sci. 2021, 22, 12437. https://doi.org/10.3390/ijms222212437
Ogura K, Ayabe Y, Harada C, Tanaka IB III, Tanaka S, Komura J-i. Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation. International Journal of Molecular Sciences. 2021; 22(22):12437. https://doi.org/10.3390/ijms222212437
Chicago/Turabian StyleOgura, Keiji, Yoshiko Ayabe, Chihiro Harada, Ignacia Braga Tanaka, III, Satoshi Tanaka, and Jun-ichiro Komura. 2021. "Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation" International Journal of Molecular Sciences 22, no. 22: 12437. https://doi.org/10.3390/ijms222212437