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Updated: Jun 2, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Using blocks of linked single nucleotide polymorphisms as highly polymorphic genetic markers for parentage analysis
Beatrix Jones1, Daniel Walsh, Lillian Werner
1Centre for Mathematical Biology, Massey University, Private Bag 102-904, North Shore Mail Centre, Auckland 0745, New Zealand, Institute of Information and Mathematical Sciences, Massey University, Private Bag 102-904, North Shore Mail Centre, Auckland 0745, New Zealand, Dana Farber Cancer Research Center, Boston, MA 02115, USA, Department of Biological Sciences, Binghamton University, PO Box 6000, Binghamton, NY 13902, USA.
This study introduces a novel method using blocks of linked single nucleotide polymorphisms (SNPs) as powerful molecular markers for parentage analysis. These multi-SNP haplotypes offer high polymorphism, rivaling traditional microsatellites for accurate paternity testing.
Area of Science:
- Genetics
- Molecular Biology
- Evolutionary Biology
Background:
- Single nucleotide polymorphisms (SNPs) are abundant genetic markers but are typically biallelic, limiting their individual utility in parentage analysis.
- Identifying numerous unlinked SNPs can be challenging, especially in non-model organisms, hindering their application in population genetics.
- Existing methods for parentage analysis often rely on microsatellites, which may not capture the full spectrum of genomic variation.
Purpose of the Study:
- To investigate the efficacy of using linked single nucleotide polymorphisms (SNPs) as multi-SNP haplotypes for reconstructing male genotypes in parentage analysis.
- To develop a novel molecular marker system that overcomes the limitations of individual biallelic SNPs for high-throughput parentage testing.
- To assess the performance of these SNP-based markers against traditional microsatellite markers in terms of parent exclusion probabilities.
Main Methods:
- Inferred haplotypes for blocks of 3 to 26 linked SNPs using Haplore and Phase 2.1 software.
- Treated each multi-SNP haplotype as a distinct allele, creating a highly polymorphic marker analogous to microsatellites.
- Conducted simulation studies using empirical haplotype frequencies from Drosophila melanogaster and Mus musculus populations.
Main Results:
- Multi-SNP haplotypes demonstrated competitive single parent exclusion probabilities compared to microsatellite loci, especially when using six or more linked SNPs.
- The developed markers exhibited modest rates of missing data and genotyping/phasing errors.
- The approach proved effective for reconstructing male genotypes in simulated polyandrous organisms with varying clutch sizes.
Conclusions:
- Linked SNP blocks, when analyzed as multi-SNP haplotypes, represent a powerful and viable alternative to microsatellites for parentage and paternity analysis.
- This method is particularly advantageous for studies focusing on the functional significance of genomic polymorphisms and for non-model organisms.
- The use of multi-SNP haplotypes offers a robust strategy for genetic marker development in population and conservation genetics.
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