Related Experiment Video
Updated: May 14, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and
Jeehae Han1, Seungjin Ryu, David M Moskowitz
1Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abstract:
Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105. Our candidate genes act in pathways implicated in aging and longevity, including neurodegeneration, cognitive function, lipid metabolism, DNA repair, and genome maintenance. By implementing custom-designed Agilent SureSelect target capture and next-generation sequencing, we discovered a total of 89 novel non-synonymous SNPs (nsSNPs) and validated 51 nsSNPs by iPLEX MassArray assays. Genotyping analysis of these novel SNPs in 410 Ashkenazi Jewish controls and 390 centenarians showed significant enrichment (5.3 fold, p = 0.02) of the p.Y318C variant in PMS2 and significant depletion (7.5 fold, p = 0.04) of the p.V465A variant in GABRR3 in centenarians compared to controls. Our study presents the potential of targeted next-generation sequencing for discovery of rare but functional genetic variation which may lead to exceptional longevity in humans.
More Related Videos
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
11:35Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)
Published on: August 21, 2016
Related Concept Videos
Pharmacogenomics: Identification of New Drug Targets
Single Nucleotide Polymorphisms-SNPs
Next-generation Sequencing
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Sanger Sequencing