Effects of genotyping errors, missing values and segregation distortion in molecular marker data on the construction of linkage maps

A simulation study was performed to investigate the effects of missing values, typing errors and distorted segregation ratios in molecular marker data on the construction of genetic linkage maps, and to compare the performance of three locus-ordering criteria (weighted least squares, maximum likelihood and minimum sum of adjacent recombination fractions criteria) in the presence of such effects. The study was based upon three linkage groups of 10 loci at 2, 6, and 10 cM spacings simulated from a doubled-haploid population of size 150. Criteria performance were assessed using the number of replicates with correctly estimated orders, the mean rank correlation between the estimated and the true order and the mean total map length. Bootstrap samples from replicates in the maximum likelihood analysis produced a measure of confidence in the estimated locus order. The effects of missing values and/or typing errors in the data are to reduce the proportion of correctly ordered maps, and this problem worsens as the distances between loci decreases. The maximum likelihood criterion is most successful at ordering loci correctly, but gives estimated map lengths, which are substantially inflated when typing errors are present. The presence of missing values in the data produces shorter map lengths for more widely spaced markers, especially under the weighted least-squares criterion. Overall, the presence of segregation distortion has little effect on this population.

[1]  Multipoint mapping and linkage based upon affected pedigree members--Genetic Analysis Workshop 6. Proceedings of a workshop. Long Beach, Mississippi, October 10-12, 1988. , 1989, Progress in clinical and biological research.

[2]  C. D. Gelatt,et al.  Optimization by Simulated Annealing , 1983, Science.

[3]  J M Olson,et al.  Monte Carlo comparison of preliminary methods for ordering multiple genetic loci. , 1990, American journal of human genetics.

[4]  M. G. Bulmer,et al.  Introduction to the mathematical theory of genetic linkage , 1962 .

[5]  C T Falk,et al.  A simple scheme for preliminary ordering of multiple loci: application to 45 CF families. , 1989, Progress in clinical and biological research.

[6]  E A Thompson,et al.  Crossover counts and likelihood in multipoint linkage analysis. , 1987, IMA journal of mathematics applied in medicine and biology.

[7]  N E Morton,et al.  Error filtration, interference, and the human linkage map. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Roeland E. Voorrips,et al.  Software for the calculation of genetic linkage maps , 2001 .

[9]  K H Buetow,et al.  Multipoint gene mapping using seriation. I. General methods. , 1987, American journal of human genetics.

[10]  Y. Ukai,et al.  Method for mapping a partial lethal-factor locus on a molecular-marker linkage map of a backcross and doubled-haploid population , 1998, Theoretical and Applied Genetics.

[11]  E S Lander,et al.  Systematic detection of errors in genetic linkage data. , 1992, Genomics.

[12]  K H Buetow,et al.  Influence of aberrant observations on high-resolution linkage analysis outcomes. , 1991, American journal of human genetics.

[13]  O. Manninen Associations between anther-culture response and molecular markers on chromosomes 2H, 3H and 4H of barley (Hordeum vulgare L.) , 2000, Theoretical and Applied Genetics.

[14]  P. Stam,et al.  Construction of integrated genetic linkage maps by means of a new computer package: JOINMAP. , 1993 .

[15]  X. Perrier,et al.  Maximum-likelihood models for mapping genetic markers showing segregation distortion. 2. F2 populations , 2004, Theoretical and Applied Genetics.

[16]  Falk Ct,et al.  A simple scheme for preliminary ordering of multiple loci: application to 45 CF families. , 1989 .

[17]  N. Morton,et al.  Standard maps of chromosome 10 , 1990, Annals of human genetics.

[18]  D. Mather,et al.  GREGOR: Software for Genetic Simulation , 1993 .

[19]  M. Lorieux,et al.  Maximum-likelihood models for mapping genetic markers showing segregation distortion. 1. Backcross populations , 2004, Theoretical and Applied Genetics.

[20]  J. Ott,et al.  Molecular and statistical approaches to the detection and correction of errors in genotype databases. , 1993, American journal of human genetics.

[21]  E. Lander,et al.  Construction of multilocus genetic linkage maps in humans. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Zivy,et al.  Segregation distortion and linkage studies in microspore-derived double haploid lines of Hordeum vulgare L. , 1992, Theoretical and Applied Genetics.