• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Mar 1993; 133(3): 737–749.
PMCID: PMC1205356

Allele Frequencies at Microsatellite Loci: The Stepwise Mutation Model Revisited

Abstract

We summarize available data on the frequencies of alleles at microsatellite loci in human populations and compare observed distributions of allele frequencies to those generated by a simulation of the stepwise mutation model. We show that observed frequency distributions at 108 loci are consistent with the results of the model under the assumption that mutations cause an increase or decrease in repeat number by one and under the condition that the product Nu, where N is the effective population size and u is the mutation rate, is larger than one. We show that the variance of the distribution of allele sizes is a useful estimator of Nu and performs much better than previously suggested estimators for the stepwise mutation model. In the data, there is no correlation between the mean and variance in allele size at a locus or between the number of alleles and mean allele size, which suggests that the mutation rate at these loci is independent of allele size.

Full Text

The Full Text of this article is available as a PDF (1.3M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Brown AH, Marshall DR, Albrecht L. Profiles of electrophoretic alleles in natural populations. Genet Res. 1975 Apr;25(2):137–143. [PubMed]
  • Bulmer MG. Protein polymorphism. Nature. 1971 Dec 17;234(5329):410–411. [PubMed]
  • Caskey CT, Pizzuti A, Fu YH, Fenwick RG, Jr, Nelson DL. Triplet repeat mutations in human disease. Science. 1992 May 8;256(5058):784–789. [PubMed]
  • Dausset J, Cann H, Cohen D, Lathrop M, Lalouel JM, White R. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics. 1990 Mar;6(3):575–577. [PubMed]
  • Deka R, Chakroborty R, Ferrell RE. A population genetic study of six VNTR loci in three ethnically defined populations. Genomics. 1991 Sep;11(1):83–92. [PubMed]
  • Dietrich W, Katz H, Lincoln SE, Shin HS, Friedman J, Dracopoli NC, Lander ES. A genetic map of the mouse suitable for typing intraspecific crosses. Genetics. 1992 Jun;131(2):423–447. [PMC free article] [PubMed]
  • Edwards A, Hammond HA, Jin L, Caskey CT, Chakraborty R. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics. 1992 Feb;12(2):241–253. [PubMed]
  • Fuerst PA, Ferrell RE. The stepwise mutation model: an experimental evaluation utilizing hemoglobin variants. Genetics. 1980 Jan;94(1):185–201. [PMC free article] [PubMed]
  • Huang TH, Cottingham RW, Jr, Ledbetter DH, Zoghbi HY. Genetic mapping of four dinucleotide repeat loci, DXS453, DXS458, DXS454, and DXS424, on the X chromosome using multiplex polymerase chain reaction. Genomics. 1992 Jun;13(2):375–380. [PubMed]
  • Hudson TJ, Engelstein M, Lee MK, Ho EC, Rubenfield MJ, Adams CP, Housman DE, Dracopoli NC. Isolation and chromosomal assignment of 100 highly informative human simple sequence repeat polymorphisms. Genomics. 1992 Jul;13(3):622–629. [PubMed]
  • Jeffreys AJ, MacLeod A, Tamaki K, Neil DL, Monckton DG. Minisatellite repeat coding as a digital approach to DNA typing. Nature. 1991 Nov 21;354(6350):204–209. [PubMed]
  • Kimura M, Ohta T. Distribution of allelic frequencies in a finite population under stepwise production of neutral alleles. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2761–2764. [PMC free article] [PubMed]
  • Kimura M, Ohta T. Stepwise mutation model and distribution of allelic frequencies in a finite population. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2868–2872. [PMC free article] [PubMed]
  • Kingman JF. A note on multidimensional models of neutral mutation. Theor Popul Biol. 1977 Jun;11(3):285–290. [PubMed]
  • Kwiatkowski DJ, Henske EP, Weimer K, Ozelius L, Gusella JF, Haines J. Construction of a GT polymorphism map of human 9q. Genomics. 1992 Feb;12(2):229–240. [PubMed]
  • Levinson G, Gutman GA. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol. 1987 May;4(3):203–221. [PubMed]
  • Litt M, Luty JA. A hypervariable microsatellite revealed by in vitro amplification of a dinucleotide repeat within the cardiac muscle actin gene. Am J Hum Genet. 1989 Mar;44(3):397–401. [PMC free article] [PubMed]
  • Moran PA. Wandering distributions and the electrophoretic profile. Theor Popul Biol. 1975 Dec;8(3):318–330. [PubMed]
  • 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. [PubMed]
  • Ramshaw JA, Coyne JA, Lewontin RC. The sensitivity of gel electrophoresis as a detector of genetic variation. Genetics. 1979 Dec;93(4):1019–1037. [PMC free article] [PubMed]
  • Richards RI, Sutherland GR. Dynamic mutations: a new class of mutations causing human disease. Cell. 1992 Sep 4;70(5):709–712. [PubMed]
  • Richards RI, Holman K, Friend K, Kremer E, Hillen D, Staples A, Brown WT, Goonewardena P, Tarleton J, Schwartz C, et al. Evidence of founder chromosomes in fragile X syndrome. Nat Genet. 1992 Jul;1(4):257–260. [PubMed]
  • Royle NJ, Clarkson RE, Wong Z, Jeffreys AJ. Clustering of hypervariable minisatellites in the proterminal regions of human autosomes. Genomics. 1988 Nov;3(4):352–360. [PubMed]
  • Slatkin M, Hudson RR. Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. Genetics. 1991 Oct;129(2):555–562. [PMC free article] [PubMed]
  • Stallings RL, Ford AF, Nelson D, Torney DC, Hildebrand CE, Moyzis RK. Evolution and distribution of (GT)n repetitive sequences in mammalian genomes. Genomics. 1991 Jul;10(3):807–815. [PubMed]
  • Müller U, Lalande M. A physical map of the human Y-chromosome short arm. Genomics. 1990 Aug;7(4):517–523. [PubMed]
  • Weber JL, May PE. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed]
  • Wehrhahn CF. The evolution of selectively similar electrophoretically detectable alleles in finite natural populations. Genetics. 1975 Jun;80(2):375–394. [PMC free article] [PubMed]
  • Weir BS. Testing for selective neutrality of electrophoretically detectable protein polymorphisms. Genetics. 1976 Nov;84(3):639–659. [PMC free article] [PubMed]
  • Wolff RK, Plaetke R, Jeffreys AJ, White R. Unequal crossingover between homologous chromosomes is not the major mechanism involved in the generation of new alleles at VNTR loci. Genomics. 1989 Aug;5(2):382–384. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...