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2003 | 13 | 3 | 385-394
Tytuł artykułu

Sampling properties of estimators of nucleotide diversity at discovered SNP sites

Treść / Zawartość
Warianty tytułu
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.
Rocznik
Tom
13
Numer
3
Strony
385-394
Opis fizyczny
Daty
wydano
2003
otrzymano
2003-03-01
poprawiono
2003-06-01
Twórcy
  • Department of Statistics, Rice University, 6100 Main Street, Mail Stop 138 Houston, TX 77005, USA
  • Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  • Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  • Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  • Center for Genome Information University of Cincinnati, Cincinnati, OH, USA
autor
  • Department of Statistics, Rice University, 6100 Main Street, Mail Stop 138 Houston, TX 77005, USA
Bibliografia
  • Bonnen P.E., Story M.D., Ashorn C.L., Buchholz T.A., Weil M.A. and Nelson D. (2000): Haplotypes at ATM identify coding-sequence variation and indicate a region of extensive linkage disequilibrium. - Am. J. Hum. Genet., Vol. 67, No. 6, pp. 1437-1451.
  • Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q. and Lander E.S. (1999): Characterization of single-nucleotide polymorphisms incoding regions of human genes. - Nat. Genet., Vol. 22, No. 3, pp. 231-238.
  • Chakraborty R. and Rao C.R. (2000): Selection biases of samples and their resolution, In: Handbook of Statistics (C.R. Rao, P.K. Sen, Eds.). -Amsterdam: Elsevier Science.
  • Clark A.G., Weiss K.M., Nickerson D.A., Taylor S.L., Buchanan A., Stengard J., Salomaa V., Vartiainen E., Perola M., Boerwinkle E., Sing C.F. (1998): Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase.- Am. J. Hum. Genet., Vol. 63, No. 2, pp. 595-612.
  • Eberle M. and Kruglyak L. (2000): An analysis of strategies for discovery of single-nucleotide polymorphisms. - Genet. Epidem., Vol. 19, No. S1, pp. S29-S35.
  • Ewens W.J. (1979): Mathematical Population Genetics. Biomathematics, Vol. 9. - Berlin: Springer.
  • Halushka M.K., Fan J.B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., LipshutzR. and Chakravarti A. (1999): Patterns of single-nucleotide polymorphisms in candidategenes for blood-pressure homeostasis. - Nat. Genet., Vol. 22, No. 3, pp. 239-247.
  • Li W.-H. (1997): Molecular Evolution. - Sunderland, MA: Sinauer Associates.
  • Nickerson D.A., Taylor S.L., Weiss K.M., Clark A.G., Hutchinson R.G., Stengard J., Salomaa V., Vartiainen E., Boerwinkle E., Sing C.F. (1998): DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. - Nat. Genet., Vol. 19, No. 3, pp. 233-240.
  • Rogers A.R., Jorde L.B. (1996): Ascertainment bias in estimates of average heterozygosity. - Am. J. Hum. Genet., Vol. 58, No. 5, pp. 1033-1041.
  • Trikka D., Fang Z., Renwick A., Jones S.H., Chakraborty R., Kimmel M., Nelson D.L.(2002): Complex SNP-based haplotypes in three human helicases demonstrate the need for ethnically-matched control populations in association studies.- Genome Res, Vol. 12, No. 4, pp. 627-639.
  • Venter J.C. et al. (2001): The sequence of the human genome.- Science, Vol. 291, No. 5507, pp. 1304-1351.
  • Wang D.G., Fan J.B., Siao C.J., Berno A., Young P., Sapolsky R., Ghandour G., Perkins N., Winchester E., Spencer J., Kruglyak L., Stein L., Hsie L., Topaloglou T., Hubbell E., Robinson E., Mittmann M., Morris M.S., Shen N., Kilburn D., Rioux J., Nusbaum C., Rozen S., Hudson T.J., Lander E.S. et al. (1998): Large-scale identification, mapping, and genotypingof single-nucleotide polymorphisms in the human genome. - Science, Vol. 280, No. 5366, pp. 1077-1082.
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.bwnjournal-article-amcv13i3p385bwm
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