Abstract
Microsatellites are short tandem repeats that are widely dispersed among eukaryotic genomes. Many of them are highly polymorphic; they have been used widely in genetic studies. Statistical properties of all measures of genetic variation at microsatellites critically depend upon the composite parameter theta = 4Nmicro, where N is the effective population size and micro is mutation rate per locus per generation. Since mutation leads to expansion or contraction of a repeat number in a stepwise fashion, the stepwise mutation model has been widely used to study the dynamics of these loci. We developed an estimator of theta, theta; (F), on the basis of sample homozygosity under the single-step stepwise mutation model. The estimator is unbiased and is much more efficient than the variance-based estimator under the single-step stepwise mutation model. It also has smaller bias and mean square error (MSE) than the variance-based estimator when the mutation follows the multistep generalized stepwise mutation model. Compared with the maximum-likelihood estimator theta; (L) by, theta; (F) has less bias and smaller MSE in general. theta; (L) has a slight advantage when theta is small, but in such a situation the bias in theta; (L) may be more of a concern.
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Selected References
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- Chakraborty R., Kimmel M., Stivers D. N., Davison L. J., Deka R. Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):1041–1046. doi: 10.1073/pnas.94.3.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chakraborty R., Weiss K. M. Genetic variation of the mitochondrial DNA genome in American Indians is at mutation-drift equilibrium. Am J Phys Anthropol. 1991 Dec;86(4):497–506. doi: 10.1002/ajpa.1330860405. [DOI] [PubMed] [Google Scholar]
- Cheung K. H., Osier M. V., Kidd J. R., Pakstis A. J., Miller P. L., Kidd K. K. ALFRED: an allele frequency database for diverse populations and DNA polymorphisms. Nucleic Acids Res. 2000 Jan 1;28(1):361–363. doi: 10.1093/nar/28.1.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deka R., Guangyun S., Smelser D., Zhong Y., Kimmel M., Chakraborty R. Rate and directionality of mutations and effects of allele size constraints at anonymous, gene-associated, and disease-causing trinucleotide loci. Mol Biol Evol. 1999 Sep;16(9):1166–1177. doi: 10.1093/oxfordjournals.molbev.a026207. [DOI] [PubMed] [Google Scholar]
- Di Rienzo A., Peterson A. C., Garza J. C., Valdes A. M., Slatkin M., Freimer N. B. Mutational processes of simple-sequence repeat loci in human populations. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3166–3170. doi: 10.1073/pnas.91.8.3166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu Y. X., Chakraborty R. Simultaneous estimation of all the parameters of a stepwise mutation model. Genetics. 1998 Sep;150(1):487–497. doi: 10.1093/genetics/150.1.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J., Tamaki K., MacLeod A., Monckton D. G., Neil D. L., Armour J. A. Complex gene conversion events in germline mutation at human minisatellites. Nat Genet. 1994 Feb;6(2):136–145. doi: 10.1038/ng0294-136. [DOI] [PubMed] [Google Scholar]
- Kimmel M., Chakraborty R. Measures of variation at DNA repeat loci under a general stepwise mutation model. Theor Popul Biol. 1996 Dec;50(3):345–367. doi: 10.1006/tpbi.1996.0035. [DOI] [PubMed] [Google Scholar]
- Kimmel M., Chakraborty R., Stivers D. N., Deka R. Dynamics of repeat polymorphisms under a forward-backward mutation model: within- and between-population variability at microsatellite loci. Genetics. 1996 May;143(1):549–555. doi: 10.1093/genetics/143.1.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nielsen R. A likelihood approach to populations samples of microsatellite alleles. Genetics. 1997 Jun;146(2):711–716. doi: 10.1093/genetics/146.2.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohta T., Kimura M. A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population. Genet Res. 1973 Oct;22(2):201–204. doi: 10.1017/s0016672300012994. [DOI] [PubMed] [Google Scholar]
- Shriver M. D., Jin L., Chakraborty R., Boerwinkle E. VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach. Genetics. 1993 Jul;134(3):983–993. doi: 10.1093/genetics/134.3.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tautz D. Notes on the definition and nomenclature of tandemly repetitive DNA sequences. EXS. 1993;67:21–28. doi: 10.1007/978-3-0348-8583-6_2. [DOI] [PubMed] [Google Scholar]
- Weber J. L., Wong C. Mutation of human short tandem repeats. Hum Mol Genet. 1993 Aug;2(8):1123–1128. doi: 10.1093/hmg/2.8.1123. [DOI] [PubMed] [Google Scholar]
- Wehrhahn C. F. The evolution of selectively similar electrophoretically detectable alleles in finite natural populations. Genetics. 1975 Jun;80(2):375–394. doi: 10.1093/genetics/80.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhivotovsky L. A., Feldman M. W. Microsatellite variability and genetic distances. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11549–11552. doi: 10.1073/pnas.92.25.11549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zouros E. Mutation rates, population sizes and amounts of electrophoretic variation of enzyme loci in natural populations. Genetics. 1979 Jun;92(2):623–646. doi: 10.1093/genetics/92.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]