Related Experiment Video
Updated: Jun 5, 2025

Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing ChIP-seq
Published on: April 19, 2013
Analysis of rare coding variants in 470,000 exome-sequenced subjects characterises contributions to risk of type 2
1UCL, UCL Genetics Institute, London, United Kingdom.
Aims:
To follow up results from an earlier study using an extended sample of 470,000 exome-sequenced subjects to identify genes associated with type 2 diabetes (T2D) and to characterise the distribution of rare variants in these genes.
Materials And Methods:
Exome sequence data for 470,000 UK Biobank participants was analysed using a combined phenotype for T2D obtained from diagnostic and prescription data. Gene-wise weighted burden analysis of rare coding variants in the new cohort of 270,000 samples was carried out for the 32 genes previously significant with uncorrected p < 0.001 along with 7 other genes previously implicated in T2D. Follow-up studies of GCK, GIGYF1, HNF1A and HNF4A used the full sample of 470,000 to investigate the effects of different categories of variant.
Results:
No novel genes were identified as exome wide significant. Rare loss of function (LOF) variants in GCK exerted a very large effect on T2D risk but more common (though still very rare) nonsynonymous variants classified as probably damaging by PolyPhen on average approximately doubled risk. Rare variants in the other three genes also had large effects on risk.
Conclusions:
In spite of the very large sample size, no novel genes are implicated. Coding variants with an identifiable effect are collectively too rare be generally useful for guiding treatment choices for most patients. The finding that some nonsynonymous variants in GCK affect T2D risk is novel but not unexpected and does not have obvious practical implications. This research has been conducted using the UK Biobank Resource.
More Related Videos
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
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
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%...
Diabetes Mellitus: Type 2 and Gestational
Single Nucleotide Polymorphisms-SNPs
Pathophysiology of Diabetes
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...