Spectrum of Point Mutations in the Human Genome and Major Subpopulations


Point mutation, often referred to as single‐nucleotide polymorphism (SNP), does not occur randomly and is dependent on the GC content and sequence context in the human genome. The spectrum of mutations in the human genome can be reliably inferred by comparing SNPs with their ancestral sequences. The direction of mutations inferred by SNPs may be measured by three approaches: directly observed frequencies of nucleotide changes, relative frequencies of nucleotide changes by normalising the nucleotide content and frequencies of nucleotide changes after excluding the CpG effect. An examination of the spectrum of mutations indicates that point mutation varies between the categorised genomic regions and has been strongly influenced by the CpG effect. There is no major difference in the mutational spectrum among the common and rare variants or among major human subpopulations; however, rare variants have higher frequency of C→T mutations, reflecting the CpG effect in the human genome.

Key Concepts:

  • Point mutation does not occur randomly in the human genome and is dependent on the GC content and sequence context.

  • Single nucleotide polymorphisms (SNPs) are the most abundant genetic variants in the human genome.

  • Mutational spectrum in the human genome and genomic regions is important for our understanding of the mechanisms of mutations, genome sequence evolution and causes of disease.

  • The direction of mutations can be reliably inferred by comparing SNPs with their ancestral sequences.

  • CpG effect has a significant influence on mutational spectrum.

  • Spectrum of mutations can be measured by three approaches: the observed frequencies of nucleotide changes, the relative frequencies and exclusion of the CpG effect.

  • Rare variants more likely reflect the recent mutational events in human populations.

Keywords: spectrum of mutations; mutation direction; single‐nucleotide polymorphisms (SNPs); nucleotide change; CpG effect; the 1000 genomes project; common variants; rare variants

Figure 1.

Inference of mutation direction by mapping human SNPs to chimpanzee genome sequences. HSP: high scoring pair.



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Web Links

CpG island searcher program (CpGi130). http://cpgislands.usc.edu/

Ensembl database. ftp://ftp.ensembl.org/pub/

MegaBLAST program. http://www.ncbi.nlm.nih.gov/blast/

NCBI dbSNP database. http://www.ncbi.nlm.nih.gov/SNP/

NCBI reference sequences. ftp://ftp.ncbi.nih.gov/genomes/

The 1000 Genomes Project. http://www.1000genomes.org/

The International HapMap Project. http://hapmap.ncbi.nlm.nih.gov/

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Zhao, Zhongming, Vuong, Huy, and Jia, Peilin(May 2013) Spectrum of Point Mutations in the Human Genome and Major Subpopulations. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020852.pub2]