Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing

Background Short tandem repeat (STR) markers are widely used in forensic DNA analysis due to their ability to provide automated and standardised typing. However, incorrect STR typing can have a significant impact on forensic outcomes.Aim In this study, we detected drop-out alleles at the SE33 locus...

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Main Authors: Hongbo Wang, Botong Shi, Liang Guo, Yingnan Zou, Bo Liu, Jun Yao, Baojie Wang, Zhengdong Wang, Xin Li, Gang Mu, Fu Ren
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Annals of Human Biology
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Online Access:https://www.tandfonline.com/doi/10.1080/03014460.2024.2418591
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author Hongbo Wang
Botong Shi
Liang Guo
Yingnan Zou
Bo Liu
Jun Yao
Baojie Wang
Zhengdong Wang
Xin Li
Gang Mu
Fu Ren
author_facet Hongbo Wang
Botong Shi
Liang Guo
Yingnan Zou
Bo Liu
Jun Yao
Baojie Wang
Zhengdong Wang
Xin Li
Gang Mu
Fu Ren
author_sort Hongbo Wang
collection DOAJ
description Background Short tandem repeat (STR) markers are widely used in forensic DNA analysis due to their ability to provide automated and standardised typing. However, incorrect STR typing can have a significant impact on forensic outcomes.Aim In this study, we detected drop-out alleles at the SE33 locus in a putative father-son pair using the Microreader™ 28 A ID System. This result could lead to a false conclusion of non-paternity.Subjects and methods To investigate the cause of the drop-out alleles, we developed a nest and touch-down PCR program for Sanger sequencing of the SE33 locus. Subsequently, we investigated the mutation frequency in 300 unrelated individuals and reviewed the results of 429 paternity tests.Results The results showed that the frequency of the G > T mutation at this locus was less than 0.01, which is a novel and rare mutation. Our analysis revealed a novel G > T mutation in the primer-binding region of both samples, which was a rare single-nucleotide mutation site in the Chinese population. This variation was found to be responsible for the drop-out alleles observed in the samples.Conclusion Our findings have important implications for optimising primer design and constructing DNA databases for forensic analysis.
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spelling doaj-art-d751e67156de49028ecaaa43f88713632025-08-20T01:57:20ZengTaylor & Francis GroupAnnals of Human Biology0301-44601464-50332024-12-0151110.1080/03014460.2024.2418591Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencingHongbo Wang0Botong Shi1Liang Guo2Yingnan Zou3Bo Liu4Jun Yao5Baojie Wang6Zhengdong Wang7Xin Li8Gang Mu9Fu Ren10Department of Human Anatomy, School of Basic Medicine, Shenyang Medical College, Shenyang, P.R. ChinaCentral Hospital of Shenyang Sujiatun, Shenyang, P.R. ChinaCentral Hospital of Shenyang Sujiatun, Shenyang, P.R. ChinaCentral Hospital of Shenyang Sujiatun, Shenyang, P.R. ChinaCentral Hospital of Shenyang Sujiatun, Shenyang, P.R. ChinaSchool of Forensic Medicine, China Medical University, Shenyang, P.R. ChinaSchool of Forensic Medicine, China Medical University, Shenyang, P.R. ChinaDepartment of Human Anatomy, School of Basic Medicine, Shenyang Medical College, Shenyang, P.R. ChinaSchool of Stomatology, Shenyang Medical College, Shenyang, P.R. ChinaThe Fourth People’s Hospital of Shenyang, Shenyang, P.R. ChinaDepartment of Human Anatomy, School of Basic Medicine, Shenyang Medical College, Shenyang, P.R. ChinaBackground Short tandem repeat (STR) markers are widely used in forensic DNA analysis due to their ability to provide automated and standardised typing. However, incorrect STR typing can have a significant impact on forensic outcomes.Aim In this study, we detected drop-out alleles at the SE33 locus in a putative father-son pair using the Microreader™ 28 A ID System. This result could lead to a false conclusion of non-paternity.Subjects and methods To investigate the cause of the drop-out alleles, we developed a nest and touch-down PCR program for Sanger sequencing of the SE33 locus. Subsequently, we investigated the mutation frequency in 300 unrelated individuals and reviewed the results of 429 paternity tests.Results The results showed that the frequency of the G > T mutation at this locus was less than 0.01, which is a novel and rare mutation. Our analysis revealed a novel G > T mutation in the primer-binding region of both samples, which was a rare single-nucleotide mutation site in the Chinese population. This variation was found to be responsible for the drop-out alleles observed in the samples.Conclusion Our findings have important implications for optimising primer design and constructing DNA databases for forensic analysis.https://www.tandfonline.com/doi/10.1080/03014460.2024.2418591Forensic geneticsSE33 locusSNP mutationDrop-out alleles
spellingShingle Hongbo Wang
Botong Shi
Liang Guo
Yingnan Zou
Bo Liu
Jun Yao
Baojie Wang
Zhengdong Wang
Xin Li
Gang Mu
Fu Ren
Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing
Annals of Human Biology
Forensic genetics
SE33 locus
SNP mutation
Drop-out alleles
title Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing
title_full Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing
title_fullStr Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing
title_full_unstemmed Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing
title_short Identification of a novel SNP mutation causing drop-out alleles in a paternity test using combined nest and touch-down PCR with Sanger sequencing
title_sort identification of a novel snp mutation causing drop out alleles in a paternity test using combined nest and touch down pcr with sanger sequencing
topic Forensic genetics
SE33 locus
SNP mutation
Drop-out alleles
url https://www.tandfonline.com/doi/10.1080/03014460.2024.2418591
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