Actual mutational research of 19 autosomal STRs based on restricted mutation model and big data
Received date: 2021-06-02
Revised date: 2021-08-18
Online published: 2021-08-31
Supported by
Supported by the National Natural Science Foundation of China No(82030058)
Short tandem repeat (STR) markers have been widely used in forensic paternity testing and individual identification, but the STR mutation might impact on the forensic result interpretation. Importantly, the STR mutation rate was underestimated due to ignoring the “hidden” mutation phenomenon in most similar studies. Considering this, we use Slooten and Ricciardi’s restricted mutation model based on big data to obtain more accurate mutation rates for each marker. In this paper, the mutations of 20 autosomal STRs loci (D3S1358, D1S1656, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D6S1043, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA; The restricted model does not include the correction factor of D6S1043, this paper calculates remaining 19 STR loci mutation rates) were investigated in 28,313 (Total: 78,739 individuals) confirmed parentage-testing cases in Chinese Han population. As a result, total 1665 mutations were found in all loci, including 1614 one-steps, 34 two-steps, 8 three-steps, and 9 nonintegral mutations. The loci-specific average mutation rates ranged from 0.00007700 (TPOX) to 0.00459050 (FGA) in trio’s and 0.00000000 (TPOX) to 0.00344850 (FGA) in duo’s. We analyzed the relationship between mutation rates of the apparent and actual, the trio’s and duo’s, the paternal and maternal, respectively. The results demonstrated that the actual mutation rates are more than the apparent mostly, and the values of μ1”/μ2”(apparent) are also greater than μ1/μ2 (actual) commonly (μ1”, μ1; μ2”, μ2 are the mutation rates of one-step and two-step). Therefore, the “hidden” mutations are identified. In addition, the mutations rates of trio’s and duo’s, the paternal and maternal, exhibit significant difference. Next, those mutation data are used to do a comparison with the studies of other Han populations in China, which present the temporal and regional disparities. Due to the large sample size, some rare mutation events, such as monozygotic (MZ) mutation and “fake four-step mutation”, are also reported in this study. In conclusion, the estimation values of actual mutations are obtained based on big data, they can not only provide basic data for the Chinese forensic DNA and population genetics databases, but also have important significance for the development of forensic individual identification, paternity testing and genetics research.
Zhiyong Liu, He Ren, Chong Chen, Jingjing Zhang, Xiaomeng Zhang, Yan Shi, Linyu Shi, Ying Chen, Feng Cheng, Li Jia, Man Chen, Qingwei Fan, Jiarong Zhang, Wanting Li, Mengchun Wang, Zilin Ren, Yacheng Liu, Ming Ni, Hongyu Sun, Jiangwei Yan . Actual mutational research of 19 autosomal STRs based on restricted mutation model and big data[J]. Hereditas(Beijing), 2021 , 43(10) : 949 -961 . DOI: 10.16288/j.yczz.21-197
| [1] | Subramanian S, Mishra RK, Singh L . Genome-wide analysis of microsatellite repeats in humans: their abundance and density in specific genomic regions. Genome Biol, 2003,4(2):R13. |
| [2] | B?r W, Brinkmann B, Budowle B, Carracedo A, Gill P, Lincoln P, Mayr W, Olaisen B . DNA recommendations. Further report of the DNA Commission of the ISFH regarding the use of short tandem repeat systems. International Society for Forensic Haemogenetics, Int J Legal Med, 1997,110(4):175-176. |
| [3] | Butler JM . Short tandem repeat typing technologies used in human identity testing. Biotechniques, 2007,43(4):2-5. |
| [4] | Kornberg A, Bertsch LL, Jackson JF, Khorana HG . Enzymatic synthesis of deoxyribonucleic acid, XVI. oligonucleotides as templates and the mechanism of their replication. Proc Natl Acad Sci USA, 1964,51(2):315-323. |
| [5] | Shao CC, Lin MX, Zhou ZH, Zhou YQ, Shen YW, Xue AM, Zhou HG, Tang QQ, Xie JH . Mutation analysis of 19 autosomal short tandem repeats in Chinese Han population from Shanghai. Int J Legal Med, 2016,130(6):1439-1444. |
| [6] | Li HX, Peng D, Wang Y, Wu RG, Zhang YM, Li R, Sun HY . Evaluation of genetic parameters of 23 autosomal STR loci in a southern Chinese Han population. Ann Hum Biol, 2018,45(4):359-364. |
| [7] | Wang HD, Kand B, Su N, He M, Zhang B, Guo YX, Zhu BF, Liao SX, Zeng ZS . Evaluation of the genetic parameters and mutation analysis of 22 STR loci in the central Chinese Han population, Int J Legal Med, 2017,131(1):103-105. |
| [8] | Qu N, Zhang XC, Liang H, Ou XL . Analysis of genetic polymorphisms and mutations at 23 autosomal STR loci in Guangdong Han population. Forensic Sci Int Genet, 2019,38:e16-e17. |
| [9] | Slooten K, Ricciardi F . Estimation of mutation probabilities for autosomal STR markers. Forensic Sci Int Genet, 2013,7(3):337-344. |
| [10] | Brinkmann B, Klintschar M, Neuhuber F, Hühne J, Rolf B . Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet, 1998,62(6):1408-1415. |
| [11] | Weber JL, Wong C . Mutation of human short tandem repeats. Hum Mol Genet, 1993,2(8):1123-1128. |
| [12] | Jin B, Su Q, Luo HB, Li YB, Wu J, Yan J, Hou YP, Liang WB, Zhang L . Mutational analysis of 33 autosomal short tandem repeat (STR) loci in southwest Chinese Han population based on trio parentage testing. Forensic Sci Int Genet, 2016,23:86-90. |
| [13] | Taylor MJ, Fisk NM . Prenatal diagnosis in multiple pregnancy. Baillieres Best Pract Res Clin Obstet Gynaecol, 2000,14(4):663-675. |
| [14] | Wurmb-Schwark NV, Schwark T, Christiansen L, Lorenz D, Oehmichen M . The use of different multiplex PCRs for twin zygosity determination and its application in forensic trace analysis. Leg Med(Tokyo), 2004,6(2):125-130. |
| [15] | Xu YJ, Li TT, Pu T, Cao RX, Long F, Chen S, Sun K, Xu R . Copy number variants and exome sequencing analysis in six pairs of Chinese monozygotic twins discordant for congenital heart disease. Twin Res Hum Genet, 2017,20(6):521-532. |
| [16] | Weber Lehmann J, Schilling E, Gradl G, Richter DC, Wiehler J, Rolf B . Finding the needle in the haystack: differentiating “identical” twins in paternity testing and forensics by ultra-deep next generation sequencing. Forensic Sci Int Genet, 2014,9:42-46. |
| [17] | Wang LF, Yang Y, Zhang XN, Quan XL, Wu YM . Tri-allelic pattern of short tandem repeats identifies the murderer among identical twins and suggests an embryonic mutational origin. Forensic Sci Int Genet, 2015,16:239-245. |
| [18] | Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Magnusson OT, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K . Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature, 2017,549(7673):519-522. |
| [19] | Valdes AM, Slatkin M, Freimer NB . Allele frequencies at microsatellite loci: the stepwise mutation model revisited. Genetics, 1993,133(3):737-749. |
| [20] | Klintschar M, Dauber EM, Ricci U, Cerri N, Immel UD, Kleiber M, Mayr WR . Haplotype studies support slippage as the mechanism of germline mutations in short tandem repeats. Electrophoresis, 2010,25(20):3344-3348. |
| [21] | Lan Q, Wang HD, Shen CM, Guo YX, Yin CY, Xie T, Fang YT, Zhou YS, Zhu BF . Mutability analysis towards 21 STR loci included in the AGCU 21+1 kit in Chinese Han population. Int J Legal Med, 2018,132(5):1287-1291. |
| [22] | Ge JY, Budowle B, Aranda XG, Planz JV, Eisenberg AJ, Chakraborty R . Mutation rates at Y chromosome short tandem repeats in Texas populations, Forensic Sci Int Genet, 2009,3(3):179-184. |
| [23] | Xu W, Wang YQ, Zhang DD, Wang DX, Zhou L, Ye XL, Zhu CG, Shi YZ . Mutation analysis of 21 autosomal short tandem repeats in Han population from Hunan, China. Ann Hum Biol. 2019,46(3):254-260. |
| [24] | Dupuy BM, Stenersen M, Egeland T, Olaisen B . Y-chromosomal microsatellite mutation rates: differences in mutation rate between and within loci, Hum Mutat, 2004,23(2):117-124. |
| [25] | Xie BB, Chen L, Yang YR, Lv YX, Chen J, Shi Y, Chen C, Zhao HY, Yu ZL, Liu YC, Fang XD, Yan JW . Genetic distribution of 39 STR loci in 1027 unrelated Han individuals from northern China. Forensic Sci Int Genet, 2015,19:205-206. |
| [26] | Chakraborty R, Stivers DN, Zhong YX . Estimation of mutation rates from parentage exclusion data: applications to STR and VNTR loci. Mutat Res, 1996,354(1):41-48. |
| [27] | Vicard P, Dawid AP . A statistical treatment of biases affecting the estimation of mutation rates. Mutat Res, 2004,547(1-2):19-33. |
| [28] | Yan JW, Liu YC, Tang H, Zhang QX, Huo ZY, Hu SN, Yu J . Mutations at 17 STR loci in Chinese population. Forensic Sci Int, 2006,162(1-3):53-54. |
| [29] | Lu DJ, Liu QL, Wu WW, Zhao H . Mutation analysis of 24 short tandem repeats in Chinese Han population. Int J Legal Med, 2012,126(2):331-335. |
| [30] | Qian XQ, Yin CY, Ji Q, Li K, Fan HT, Yu YF, Bu FL, Hu LL, Wang JW, Mu HF, Haigh S, Chen F . Mutation rate analysis at 19 autosomal microsatellites. Electrophoresis, 2015,36(14):1633-1639. |
| [附录] | 附录涉及的参考文献(References): |
| [1] | Yan JW, Liu YC, Tang H, Zhang QX, Huo ZY, Hu SN, Yu J . Mutations at 17 STR loci in Chinese population. Forensic Sci Int, 2006,162(1-3):53-54. |
| [2] | Qian XQ, Yin CY, Ji Q, Li K, Fan HT, Yu YF, Bu FL, Hu LL, Wang JW, Mu HF . Mutation rate analysis at 19 autosomal microsatellites. Electrophoresis, 2015,36(14):1633-1639. |
| [3] | Li HX, Peng D, Wang Y, Wu RG, Zhang YM, Li R, Sun HY . Evaluation of genetic parameters of 23 autosomal STR loci in a Southern Chinese Han population, Ann Hum Biol, 2018,45(4):359-364. |
| [4] | Wang. HD, Kang B, Su N, He M, Zhang B, Guo YX, Zhu BF, Liao. SX, Zeng ZS. Evaluation of the genetic parameters and mutation analysis of 22 STR loci in the central Chinese Han population. Int J Legal Med, 2016,131(1):103-105. |
| [5] | Shao CC, Lin MX, Zhou ZH, Zhou YQ, Shen YW, Xue AM, Zhou HG, Tang QQ, Xie JH . Mutation analysis of 19 autosomal short tandem repeats in Chinese Han population from Shanghai. Int J Legal Med, 2016,130(6):1439-1444. |
| [6] | Yang MQ, Ren Z, Ji JY, Zhou H, Zhang HL, Dai JL, Wang J, Huang J . Population genetic data and mutations of 22 autosomal STR loci in Guizhou Han population. Forensic Sci Int Genet, 2017,29:e29-e30. |
| [7] | Sun LJ, Shi K, Tan L, Zhang Q, Fu LH, Zhang XJ, Fu GP, Li SJ, Cong B . Analysis of genetic polymorphisms and mutations at 19 STR loci in Hebei Han population. Forensic Sci Int Genet, 2017,31:e50-e51. |
| [8] | Zhang XF, Liu LL, Xie RF, Wang GY, Shi Y, Gu T, Hu LP, Nie SJ . Population data and mutation rates of 20 autosomal STR loci in a Chinese Han population from Yunnan Province, Southwest China. Int J Legal Med, 2018,132(4):1083-1085. |
| [9] | Qu N, Zhang XC, Liang H, XL Ou . Analysis of genetic polymorphisms and mutations at 23 autosomal STR loci in Guangdong Han population. Forensic Sci Int Genet, 2019,38:e16-e17. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
