Elsevier

Genomics

Volume 12, Issue 2, February 1992, Pages 377-387
Genomics

Identification of clusters of biallelic polymorphic sequence-tagged sites (pSTSs) that generate highly informative and automatable markers for genetic linkage mapping

https://doi.org/10.1016/0888-7543(92)90388-9Get rights and content

Abstract

Using a combination of denaturing gradient gel electrophoresis and direct DNA sequencing, we have found that multiple (4 to 7) biallelic sequence polymorphisms can be located within short DNA segments, 300 to 2400 bp. Here, we report on the identification of three clusters of DNA polymorphisms, one in each of the constant regions of the human T cell receptor α and β gene complexes on human chromosomes 14 and 7, respectively, and a third among the human t-RNA genes on human chromosome 14. The frequency of these polymorphisms and the extent of linkage disequilibrium between individual polymorphisms have been determined using a semiautomated DNA typing system combining DNA target amplification by the polymerase chain reaction with the analysis of internal sequence polymorphisms by a colorimetric oligonucleotide ligation assay. We have found that individual biallelic polymorphisms in each cluster are often in partial linkage disequilibrium with one another. This partial linkage disequilibrium permits the combined use of three to four markers in a cluster to generate a haplotype with high levels of heterozygosity, 71 to 88%. Therefore, clusters of physically linked biallelic polymorphisms provide an automatable and highly informative type of genetic marker for general linkage analysis as well as an attractive alternative marker system for fine-point mapping of disease-causing genes and phenotypic traits relative to their framework locations in the genome.

References (38)

  • D.W. Cox et al.

    DNA restriction fragments associated with α1-antitrypsin indicate a single origin for deficiency allele PIZ

    Nature

    (1985)
  • H. Donis-Keller et al.

    Highly polymorphic RFLP probes as diagnostic tools

  • S.G. Fischer et al.

    DNA fragments differing by single base-pair substitutions are separated in denaturing gradient gels: Correspondence with melting theory

  • A.J. Jeffreys et al.

    DNA “fingerprints” and segregation analysis of multiple markers in human pedigrees

    Amer. J. Hum. Genet

    (1986)
  • A.J. Jeffreys et al.

    Amplification of human minisatellites by the polymerase chain reaction: Towards DNA fingerprinting of single cells

    Nucleic Acids Res

    (1988)
  • M. Kimura
  • K.A. Kretz et al.

    Direct sequencing from low-melt agarose with Sequenase

    Nucleic Acid Res

    (1989)
  • U. Landegren et al.

    A ligase-mediated gene detection technique

    Science

    (1988)
  • E.S. Lander

    Research on DNA typing catching up with courtroom application

    Am. J. Hum. Genet

    (1991)
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