Sampling properties of estimators of nucleotide diversity at discovered SNP sites

• Autorzy: Alexander Renwick , Penelope E. Bonnen , Dimitra Trikka , David L. Nelson , Ranajit Chakraborty , Marek Kimmel
• Języki publikacji: EN

Abstrakty

EN

SNP sites are generally discovered by sequencing regions of the human genome in a limited number of individuals. This may leave SNP sites present in the region, but containing rare mutant nucleotides, undetected. Consequently, estimates of nucleotide diversity obtained from assays of detected SNP sites are biased. In this research we present a statistical model of the SNP discovery process, which is used to evaluate the extent of this bias. This model involves the symmetric Beta distribution of variant frequencies at SNP sites, with an additional probability that there is no SNP at any given site. Under this model of allele frequency distributions at SNP sites, we show that nucleotide diversity is always underestimated. However, the extent of bias does not seem to exceed 10-15% for the analyzed data. We find that our model of allele frequency distributions at SNP sites is consistent with SNP statistics derived based on new SNP data at ATM, BLM, RQL and WRN gene regions. The application of the theory to these new SNP data as well as to the literature data at the LPL gene region indicates that in spite of ascertainment biases, the observed differences of nucleotide diversity across these gene regions are real. This provides interesting evidence concerning the heterogeneity of the rates of nucleotide substitution across the genome.

Słowa kluczowe

EN

nucleotide diversity; molecular evolution; single nucleotide polymorphisms; ascertainment bias

• Wydawca: University of Zielona Gora Press
• Czasopismo: International Journal of Applied Mathematics and Computer Science
• Rocznik: 2003
• Tom: 13
• Numer: 3
• Strony: 385-394

Daty

wydano

2003

otrzymano

2003-03-01

poprawiono

2003-06-01

Twórcy

autor

Alexander Renwick

• Department of Statistics, Rice University, 6100 Main Street, Mail Stop 138 Houston, TX 77005, USA

autor

Penelope E. Bonnen

• Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

autor

Dimitra Trikka

• Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

autor

David L. Nelson

• Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

autor

Ranajit Chakraborty

• Center for Genome Information University of Cincinnati, Cincinnati, OH, USA

autor

Marek Kimmel

• Department of Statistics, Rice University, 6100 Main Street, Mail Stop 138 Houston, TX 77005, USA

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