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Am J Hum Genet. May 1993; 52(5): 947–957.
PMCID: PMC1682055

Ordering genes: controlling the decision-error probabilities.


Determination of the relative gene order on chromosomes is of critical importance in the construction of human gene maps. In this paper we develop a sequential algorithm for gene ordering. We start by comparing three sequential procedures to order three genes on the basis of Bayesian posterior probabilities, maximum-likelihood ratio, and minimal recombinant class. In the second part of the paper we extend sequential procedure based on the posterior probabilities to the general case of g genes. We present a theorem that states that the predicted average probability of committing a decision error, associated with a Bayesian sequential procedure that accepts the hypothesis of a gene-order configuration with posterior probability equal to or greater than pi *, is smaller than 1 - pi *. This theorem holds irrespective of the number of genes, the genetic model, and the source of genetic information. The theorem is an extension of a classical result of Wald, concerning the sum of the actual and the nominal error probabilities in the sequential probability ratio test of two hypotheses. A stepwise strategy for ordering a large number of genes, with control over the decision-error probabilities, is discussed. An asymptotic approximation is provided, which facilitates the calculations with existing computer software for gene mapping, of the posterior probabilities of an order and the error probabilities. We illustrate with some simulations that the stepwise ordering is an efficient procedure.

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Selected References

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  • Buetow KH. Influence of aberrant observations on high-resolution linkage analysis outcomes. Am J Hum Genet. 1991 Nov;49(5):985–994. [PMC free article] [PubMed]
  • Buetow KH, Shiang R, Yang P, Nakamura Y, Lathrop GM, White R, Wasmuth JJ, Wood S, Berdahl LD, Leysens NJ, et al. A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates. Am J Hum Genet. 1991 May;48(5):911–925. [PMC free article] [PubMed]
  • Donis-Keller H, Green P, Helms C, Cartinhour S, Weiffenbach B, Stephens K, Keith TP, Bowden DW, Smith DR, Lander ES, et al. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. [PubMed]
  • Foroud T, Wei S, Ziv Y, Sobel E, Lange E, Chao A, Goradia T, Huo Y, Tolun A, Chessa L, et al. Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium. Am J Hum Genet. 1991 Dec;49(6):1263–1279. [PMC free article] [PubMed]
  • Fujimori M, Wells SA, Jr, Nakamura Y. Fine-scale mapping of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1). Am J Hum Genet. 1992 Feb;50(2):399–403. [PMC free article] [PubMed]
  • Goradia TM, Lange K. Multilocus ordering strategies based on sperm typing. Ann Hum Genet. 1990 Jan;54(Pt 1):49–77. [PubMed]
  • Huang TH, Hejtmancik JF, Edwards A, Pettigrew AL, Herrera CA, Hammond HA, Caskey CT, Zoghbi HY, Ledbetter DH. Linkage of the gene for an X-linked mental retardation disorder to a hypervariable (AGAT)n repeat motif within the human hypoxanthine phosphoribosyltransferase (HPRT) locus (Xq26). Am J Hum Genet. 1991 Dec;49(6):1312–1319. [PMC free article] [PubMed]
  • Keats BJ, Pollack MS, McCall A, Wilensky MA, Ward LJ, Lu M, Zoghbi HY. Tight linkage of the gene for spinocerebellar ataxia to D6S89 on the short arm of chromosome 6 in a kindred for which close linkage to both HLA and F13A1 is excluded. Am J Hum Genet. 1991 Nov;49(5):972–977. [PMC free article] [PubMed]
  • Lathrop GM, Chotai J, Ott J, Lalouel JM. Tests of gene order from three-locus linkage data. Ann Hum Genet. 1987 Jul;51(Pt 3):235–249. [PubMed]
  • Lebo RV, Lynch ED, Bird TD, Golbus MS, Barker DF, O'Connell P, Chance PF. Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers. Am J Hum Genet. 1992 Jan;50(1):42–55. [PMC free article] [PubMed]
  • MORTON NE. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed]
  • Thompson EA. Information gain in joint linkage analysis. IMA J Math Appl Med Biol. 1984;1(1):31–49. [PubMed]

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