Elsevier

Genomics

Volume 53, Issue 3, 1 November 1998, Pages 251-259
Genomics

Regular Article
Linkage of Asthma to Markers on Chromosome 12 in a Sample of 240 Families Using Quantitative Phenotype Scores

https://doi.org/10.1006/geno.1998.5485Get rights and content

Abstract

We present evidence of linkage between markers on chromosome 12 and asthma using the BETA program for nonparametric single- and multipoint linkage analysis. We have used quantitative scores as our phenotypic variables, combining data into indices for asthma and atopy and maximizing heritability. The largest single-locus LODs were achieved for asthma: D12S342 and asthma score (LOD 2.255), D12S324 and asthma affection (LOD 2.214), and D12S366 and wheeze (LOD 3.307). The region of interest identified using multipoint analysis, with a maximum LOD of 2.29, centers around D12S97 at location 173.5 cM with a standard error of 6.5 for the asthma score and close agreement for asthma affection and wheeze. Such evidence merits further investigation of this area in an attempt to define the region with greater precision with a view to identifying candidate genes. We hope that the methods presented will encourage researchers to use phenotypic information in a way that encourages meta-analysis.

References (37)

  • A Collins et al.

    Mapping a disease locus by allelic association

    Proc. Natl. Acad. Sci. USA

    (1998)
  • A Collins et al.

    Trials of the β model for complex inheritance

    Proc. Natl. Acad. Sci. USA

    (1996)
  • W.O.C.M Cookson et al.

    Investigating the asthma phenotype

    Clin. Exp. Allergy

    (1998)
  • I.J.M Doull et al.

    Allelic association of markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness

    Am. J. Respir. Crit. Care Med.

    (1996)
  • D.S Falconer

    Introduction to Quantitative Genetics

    (1960)
  • L.N Hazel

    The genetic basis for constructing selection indices

    Genetics

    (1943)
  • O Kempthorne

    An Introduction to Genetic Statistics

    (1957)
  • L Kruglyak et al.

    Parametric and nonparametric linkage analysis: A unified multipoint approach

    Am. J. Hum. Genet.

    (1996)
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    N. E. MortonD. C. RaoJ.-M. Lalouel

    1

    To whom correspondence should be addressed at Human Genetics, Level G, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK. Telephone: 01703 796535. Fax: 01703 798416. E-mail:[email protected].

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