Skip to main content
Article thumbnail
Location of Repository

Detecting Linkage between a Trait and a Marker in a Random Mating Population without Pedigree Record

By Shuhei Mano, Takaho A. Endo, Akira Oka, Akira Ozawa, Takashi Gojobori and Hidetoshi Inoko

Abstract

Modern linkage-based approaches employing extended pedigrees are becoming powerful tools for localizing complex quantitative trait loci. For these linkage mapping methods, it is necessary to reconstruct extended pedigrees which include living individuals, using extensive pedigree records. Unfortunately, such records are not always easy to obtain and application of the linkage-based approaches has been restricted. Within a finite population under random mating, latent inbreeding rather than non-random inbreeding by consanguineous marriages is expected to occur and is attributable to coalescence in a finite population. Interestingly, it has been revealed that significant random inbreeding exists even in general human populations. Random inbreeding should be used to detect the hidden coancestry between individuals for a particular chromosomal position and it could also have application in linkage mapping methods. Here we present a novel method, named finite population based linkage mapping (FPL) method, to detect linkage between a quantitative trait and a marker via random inbreeding in a finite population without pedigree records. We show how to estimate coancestry for a chromosomal position between individuals by using multipoint Bayesian estimation. Subsequently, we describe the FPL method for detecting linkage via interval mapping method using a nonparametric test. We show that the FPL method does work via simulated data. For a random sample from a finite population, the FPL method is more powerful than a standard pedigree-based linkage mapping method with using genotypes of all parents of the sample. In addition, the FPL method was demonstrated by actual microsatellite genotype data of 750 Japanese individuals that are unrelated according to pedigree records to map a known Psoriasis susceptible locus. For samples without pedigree records, it was suggested that the FPL method require limited number of individuals, therefore would be better than other methods using thousands of individuals

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2655708
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (1973). A model of mutation appropriate to estimate number of electrophoretically detectable alleles in a finite population.
    2. (2003). A polygenic basis for late-onset disease.
    3. (2002). An estimator for pairwise relatedness using molecular markers.
    4. (1974). An extension of the probability approach to genetic relationships: one locus.
    5. (2001). Are rare variants responsible for susceptibility to complex diseases?
    6. (1999). Estimation of pairwise relatedness with molecular markers.
    7. (1972). Genetic information given by relative.
    8. (1998). Genetics and analysis of quantitative traits.
    9. (2009). Genome-wide scan reveals associaction of psoriasis with IL-23 and NF-kB pathways.
    10. (2004). Ignoring linkage disequilibrium among tightly linked markers induces false-positive evidence of linkage for affected sib pair analysis.
    11. (2004). Localization and identification of human quantitative trait loci: King harvest has surely come.
    12. (1965). Measurement of inbreeding from the frequency of marriages between persons of the same surname.
    13. (2005). Measures of human population structure show heterogeneity among genomic regions.
    14. (1987). Molecular evolutionary genetics.
    15. (1998). Multipoint quantitative trait linkage analysis in general pedigrees.
    16. (1965). Random and nonrandom inbreeding.
    17. (2007). Recent human effective population size estimated from linkage disequilibrium.
    18. (2006). Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene.
    19. (1975). The estimation of pairwise relationships.
    20. (1951). The genetical structure of populations.
    21. (1995). The origin of human populations; genetic, linguistic, and archeological data.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.