Development and evaluation of a novel panel containing 188 microhaplotypes for 2nd-degree kinship testing in the Hebei Han population

Du, Qingqing; Ma, Guanju; Lu, Chaolong; Wang, Qian; Fu, Lihong; Cong, Bin; Li, Shujin

doi:10.1016/j.fsigen.2023.102855

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…The above tools have been used in the construction of next-generation sequencing kits containing multiple single-nucleotide polymorphism ( Zhao et al, 2021 ) or microhaplotype ( Du et al, 2023 ) markers. In the relevant studies, family surveys were carried out at the same time, and the results of the two types of research were found to be similar; see Fig.…”

Section: Methods and Resultsmentioning

confidence: 99%

“…4 of (Zhao et al, 2021) and Fig. 4 of (Du et al 2023), which illustrate the effectiveness of the simulation tools in real-life cases.…”

Section: Application Of the Packagementioning

confidence: 97%

“…In order to conduct complex kinship identification, it is essential to evaluate the practicality of specific panels or marker types ( Mo et al, 2018 ; Li et al, 2019 ; Liu et al, 2020 ; Wu et al, 2021 ; Zhao et al, 2021 ; Du et al, 2023 ). Such assessments often necessitate pedigree investigations based on real cases or computer simulations.…”

Section: Introductionmentioning

confidence: 99%

“…As kinship complexity increases, so too does the difficulty of investigating real cases: either the target cases are rare in the population (such as inbreeding cases); or the confirmation of the participants is challenging (for example, to confirm the relationship between a pair of first cousins, their common grandparents, and their parents who are full-siblings to each other should also be detected), making simulation a more realistic method. There are several application scenarios for simulation methods in this field, including i) assessing the sensitivity and specificity of specific markers in identification ( Phillips et al, 2012 ; Mo et al, 2018 ; Liu et al, 2020 ; Du et al, 2023 ); ii) comparing different parameters in the same identification based on the same panel, e.g., LR calculated based on length information vs LR calculated based on length + sequence information ( Staadig and Tillmar, 2019 ; Liu et al, 2020 ); iii) estimating the required number of markers in specific identification using curve fitting, through a quantity of simulation based on different subsets of current loci combinations, when the current combination cannot meet the identification requirements ( Mo et al, 2016 ; Du et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

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An approach to unified formulae for likelihood ratio calculation in pairwise kinship analysis

Ma,

Wang,

Cong

et al. 2024

Front. Genet.

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Introduction: The likelihood ratio (LR) can be an efficient means of distinguishing various relationships in forensic fields. However, traditional list-based methods for derivation and presentation of LRs in distant or complex relationships hinder code editing and software programming. This paper proposes an approach for a unified formula for LRs, in which differences in participants’ genotype combinations can be ignored for specific identification. This formula could reduce the difficulty of by-hand coding, as well as running time of large-sample-size simulation.Methods: The approach is first applied to a problem of kinship identification in which at least one of the participants is alleged to be inbred. This can be divided into two parts: i) the probability of different identical by descent (IBD) states according to the alleged kinship; and ii) the ratio of the probability that specific genotype combination can be detected assuming the alleged kinship exists between the two participants to the similar probability assuming that they are unrelated, for each state. For the probability, there are usually recognized results for common identification purposes. For the ratio, subscript letters representing IBD alleles of individual A’s alleles are used to eliminate differences in genotype combinations between the two individuals and to obtain a unified formula for the ratio in each state. The unification is further simplified for identification cases in which it is alleged that both of the participants are outbred. Verification is performed to show that the results obtained with the unified and list-form formulae are equivalent.Results: A series of unified formulae are derived for different identification purposes, based on which an R package named KINSIMU has been developed and evaluated for use in large-size simulations for kinship analysis. Comparison between the package with two existing tools indicated that the unified approach presented here is more convenient and time-saving with respect to the coding process for computer applications compared with the list-based approach, despite appearing more complicated. Moreover, the method of derivation could be extended to other identification problems, such as those with different hypothesis sets or those involving multiple individuals.Conclusion: The unified approach of LR calculation can be beneficial in kinship identification field.

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Section: Methods and Resultsmentioning

confidence: 99%

“…4 of (Zhao et al, 2021) and Fig. 4 of (Du et al 2023), which illustrate the effectiveness of the simulation tools in real-life cases.…”

Section: Application Of the Packagementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An approach to unified formulae for likelihood ratio calculation in pairwise kinship analysis

Ma,

Wang,

Cong

et al. 2024

Front. Genet.

Self Cite

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“…Several candidate MH loci [3,[10][11][12][13][14][15][16][17] were identified via the 1000 genomes project [18]. They were tested on either Ion PGM [19], Ion S5 [11,20], NextSeq 500 [14,21], or MiSeq MPS platforms [11][12][13]16,22,23].…”

Section: Introductionmentioning

confidence: 99%

Performance of a 74-Microhaplotype Assay in Kinship Analyses

Tomas,

Rodrigues,

Jønck

et al. 2024

Genes

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Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study, we analysed 74 previously defined MHs in two of the populations that our laboratory provides with forensic genetic services, Danes and Greenlanders. In addition to the 229 SNPs that originally made up the 74 MHs, 66 SNPs and 3 indels were identified in the two populations, and 45 of these variants were included in new definitions of the MHs, whereas 24 SNPs were considered rare and of little value for case work. The average effective number of alleles (Ae) was 3.2, 3.0, and 2.6 in Danes, West Greenlanders, and East Greenlanders, respectively. High levels of linkage disequilibrium were observed in East Greenlanders, which reflects the characteristics of this population that has a small size, and signs of admixture and substructure. Pairwise kinship simulations of full siblings, half-siblings, first cousins, and unrelated individuals were performed using allele frequencies from MHs, STRs and SNPs from Danish and Greenlandic populations. The MH panel outperformed the currently used STR and SNP marker sets and was able to differentiate siblings from unrelated individuals with a 0% false positive rate and a 1.1% false negative rate using an LR threshold of 10,000 in the Danish population. However, the panel was not able to differentiate half-siblings or first cousins from unrelated individuals. The results generated in this study will be used to implement MHs as investigative markers for relationship testing in our laboratory.

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Feasibility study of a single‐primer extension‐based microhaplotype NGS system

Zhu,

Shu,

Wang

et al. 2024

Electrophoresis

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DNA degradation has been a thorny problem in forensic science. Shortening the amplicon length of the genetic markers improves the analysis of degraded DNA effectively. Microhaplotype (MH) has been proposed as a potential genetic marker that can be used for degraded DNA analysis. In the present study, a 146‐plex MH‐next‐generation sequencing (NGS) system with an average Ae of 6.876 was constructed. Unlike other MH studies, a single‐primer extension (SPE)‐based NGS library preparation method was used to improve the detection of MH markers for degraded DNA. SPE employs a locus‐specific and universal primer to amplify target fragments, reducing the necessity for complete fragment sequences. SPE might effectively mitigate the impact of degradation on amplification. However, SPE produces amplicons of varying lengths, posing challenges in allele calling for SPE‐NGS data. To address this issue, this study proposed a flexible allele‐calling strategy to improve amplicon detection. In addition, this study evaluated the forensic efficacy of the system using 12 low‐template samples (from 1 ng to 7.8 pg), 10 mock‐degraded DNA with various degrees of degradation, and 8 forensic casework samples. When the template is as low as 7.8 pg, our system can accurately detect at least 37 loci and achieves a random match probability (RMP) of 10−30 using the complete allele‐calling strategy. Eighty‐two loci can be detected, and RMP can reach 10−54 using a flexible allele‐calling strategy. After 150 min of 98°C treatment, 36 loci can still be detected, and an RMP of 10−5 can be obtained using the flexible allele‐calling strategy. Furthermore, the number of single nucleotide polymorphism detected at different DNA amounts and degradation levels suggests that the SPE method combined with a flexible allele‐calling strategy is effective.

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Development and evaluation of a novel panel containing 188 microhaplotypes for 2nd-degree kinship testing in the Hebei Han population

Cited by 8 publications

References 39 publications

An approach to unified formulae for likelihood ratio calculation in pairwise kinship analysis

An approach to unified formulae for likelihood ratio calculation in pairwise kinship analysis

Performance of a 74-Microhaplotype Assay in Kinship Analyses

Feasibility study of a single‐primer extension‐based microhaplotype NGS system

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