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. 1993 Jun;52(6):1102–1110.

Incorrect specification of marker allele frequencies: effects on linkage analysis.

N B Freimer 1, L A Sandkuijl 1, S M Blower 1
PMCID: PMC1682284  PMID: 8503444

Abstract

Most current linkage analyses make use of highly polymorphic DNA markers. Assigning correct allele frequencies for these markers may be extremely difficult in particular study populations. Designation of erroneous frequencies may result in false-positive evidence for linkage, as well as in failure to correctly exclude linkage. These effects are most pronounced in small pedigrees with key individuals unavailable for typing. The power to correctly detect true linkage does not appear to be greatly affected by inaccurate allele frequencies. Before linkage analyses are performed for specific pedigrees, it is recommended that simulation analyses be performed, followed by uncertainty and sensitivity analyses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blower S. M., Hartel D., Dowlatabadi H., Anderson R. M., May R. M. Drugs, sex and HIV: a mathematical model for New York City. Philos Trans R Soc Lond B Biol Sci. 1991 Feb 28;331(1260):171–187. doi: 10.1098/rstb.1991.0006. [DOI] [PubMed] [Google Scholar]
  2. Bowcock A. M., Hebert J. M., Mountain J. L., Kidd J. R., Rogers J., Kidd K. K., Cavalli-Sforza L. L. Study of an additional 58 DNA markers in five human populations from four continents. Gene Geogr. 1991 Dec;5(3):151–173. [PubMed] [Google Scholar]
  3. Devlin B., Risch N., Roeder K. Estimation of allele frequencies for VNTR loci. Am J Hum Genet. 1991 Apr;48(4):662–676. [PMC free article] [PubMed] [Google Scholar]
  4. Edwards A., Hammond H. A., Jin L., Caskey C. T., Chakraborty R. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics. 1992 Feb;12(2):241–253. doi: 10.1016/0888-7543(92)90371-x. [DOI] [PubMed] [Google Scholar]
  5. Kidd J. R., Black F. L., Weiss K. M., Balazs I., Kidd K. K. Studies of three Amerindian populations using nuclear DNA polymorphisms. Hum Biol. 1991 Dec;63(6):775–794. [PubMed] [Google Scholar]
  6. Knowles J. A., Vieland V. J., Gilliam T. C. Perils of gene mapping with microsatellite markers. Am J Hum Genet. 1992 Oct;51(4):905–909. [PMC free article] [PubMed] [Google Scholar]
  7. Kruger S. D., Turner W. J., Kidd K. K. The effects of requisite assumptions on linkage analyses of manic-depressive illness with HLA. Biol Psychiatry. 1982 Oct;17(10):1081–1099. [PubMed] [Google Scholar]
  8. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet. 1985 May;37(3):482–498. [PMC free article] [PubMed] [Google Scholar]
  9. Litt M., Luty J. A. 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] [Google Scholar]
  10. Morton N. E. Analysis of crossingover in man. Cytogenet Cell Genet. 1978;22(1-6):15–36. doi: 10.1159/000130916. [DOI] [PubMed] [Google Scholar]
  11. Sampson J. R., Janssen L. A., Sandkuijl L. A. Linkage investigation of three putative tuberous sclerosis determining loci on chromosomes 9q, 11q, and 12q. The Tuberous Sclerosis Collaborative Group. J Med Genet. 1992 Dec;29(12):861–866. doi: 10.1136/jmg.29.12.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sandkuyl L., Ott J. Determining informativity of marker typing for genetic counseling in a pedigree. Hum Genet. 1989 May;82(2):159–162. doi: 10.1007/BF00284050. [DOI] [PubMed] [Google Scholar]
  13. Schellenberg G. D., Pericak-Vance M. A., Wijsman E. M., Moore D. K., Gaskell P. C., Jr, Yamaoka L. A., Bebout J. L., Anderson L., Welsh K. A., Clark C. M. Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. Am J Hum Genet. 1991 Mar;48(3):563–583. [PMC free article] [PubMed] [Google Scholar]
  14. Valdes A. M., Slatkin M., Freimer N. B. Allele frequencies at microsatellite loci: the stepwise mutation model revisited. Genetics. 1993 Mar;133(3):737–749. doi: 10.1093/genetics/133.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Van Broeckhoven C., Backhovens H., Cruts M., De Winter G., Bruyland M., Cras P., Martin J. J. Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3. Nat Genet. 1992 Dec;2(4):335–339. doi: 10.1038/ng1292-335. [DOI] [PubMed] [Google Scholar]
  16. Weber J. L., May P. E. 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] [Google Scholar]
  17. Weeks D. E., Lehner T., Squires-Wheeler E., Kaufmann C., Ott J. Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis. Genet Epidemiol. 1990;7(4):237–243. doi: 10.1002/gepi.1370070402. [DOI] [PubMed] [Google Scholar]

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