Molecular Biotechnology

, Volume 48, Issue 1, pp 1–6 | Cite as

An Excess of G over C Nucleotides in Mutagenesis of Human Genetic Diseases

  • Li Xiao
  • Wanping Sun
  • Jia Zhang
  • Yanping Zhou
  • Linling Chen
  • Hanlin Gao
  • Pierre Sirois
  • Kai LiEmail author


Strand asymmetries in DNA evolution, including indel and single nucleotide substitutions, were reported in prokaryotes. Recently, an excess of G>A over C>T substitutions in hemophilia B patients was recognized in our molecular diagnostic practices. Further analysis demonstrated biased point mutations between sense and antisense strands when unique changes in factor IX were counted. Similar mutation spectra of factor IX and the HGMD prompted us to speculate that the excess of G>A over C>T may be present in genes other than factor IX. Data from nine genes (each has ≥100 missense mutations) retrieved from HGMD, international factor IX database, and Dr. Sommer’s lab database in the City of Hope National Medical Center, Duarte, CA, USA were analyzed for their point mutation spectra. Similar to factor IX, all genes selected in this study have biased G>A over C>T unique mutations when nonsense mutations were excluded. The biased missense point mutations were recently convincingly documented by the statistic data of categorized missense mutation in HGMD. The consistence of the genetic observation and the genomic data from HGMD strongly indicate that biased point mutations, possibly a phenotypic selection, are more widespread than previously thought. The biased mutations have immediate clinical impact in molecular diagnostics.


Genetic disease Mutagenesis Single nucleotide substitution Strand bias Factor IX 



Dr. K. Li is indebted to Dr. S.S. Sommer for his encouragement about this and related mutagenesis studies. The data analysis was initially done in Dr. Sommer’s Laboratory at the City of Hope National Medical Center (Duarte, CA, USA). This study was partially supported by Chinese National 863 major grant (2008AA02Z436) and National Natural Science Foundation of China (No. 30970877).


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Li Xiao
    • 1
    • 2
  • Wanping Sun
    • 1
    • 2
  • Jia Zhang
    • 1
    • 3
  • Yanping Zhou
    • 1
  • Linling Chen
    • 4
  • Hanlin Gao
    • 4
  • Pierre Sirois
    • 5
  • Kai Li
    • 1
    Email author
  1. 1.Department of Molecular Diagnostics, College of PharmacySoochow UniversitySuzhouChina
  2. 2.Department of Molecular Medicine CenterThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
  3. 3.Genomics Institute of the Novartis Research FoundationSan DiegoUSA
  4. 4.Department of Molecular DiagnosticsCity of Hope National Medical CenterDuarteUSA
  5. 5.CHUL Research CenterLaval UniversityQuebecCanada

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