Distribution and Effects of Nonsense Polymorphisms in Human Genes
2008

Distribution and Effects of Nonsense Polymorphisms in Human Genes

Sample size: 36712 publication 10 minutes Evidence: moderate

Author Information

Author(s): Yamaguchi-Kabata Yumi, Shimada Makoto K., Hayakawa Yosuke, Minoshima Shinsei, Chakraborty Ranajit, Gojobori Takashi, Imanishi Tadashi

Primary Institution: Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan

Hypothesis

How do genetic variations, specifically nonsense polymorphisms, affect gene function?

Conclusion

Nonsense SNPs exist at a lower density than nonsynonymous SNPs, indicating that they may have more severe effects on gene function.

Supporting Evidence

  • Nonsense SNPs were found to be more common in genes involving kinase activity and transport.
  • 581 of the nonsense SNPs were predicted to cause nonsense-mediated decay (NMD) of transcripts.
  • Only eight of 1,183 nonsense SNPs matched known pathological variants in the OMIM database.

Takeaway

This study looked at tiny changes in our genes that can stop proteins from being made properly, and found that these changes are less common but can be more harmful than other types of changes.

Methodology

Analyzed publicly available polymorphisms in dbSNP for single nucleotide polymorphisms located in the exons of 36,712 known and predicted protein-coding genes.

Limitations

The biological effects of most nonsense SNPs have not yet been reported.

Statistical Information

P-Value

0.0033

Statistical Significance

p<0.005

Digital Object Identifier (DOI)

10.1371/journal.pone.0003393

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