• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Dec 1, 1996; 24(23): 4841–4843.
PMCID: PMC146303

Molecular haplotyping of genetic markers 10 kb apart by allele-specific long-range PCR.


Haplotypes, combinations of polymorphic markers in a chromosome, are critical for genome diversity research. However, their utility in population samplings is compromised by uncertain linkage phase determinations from unrelated individuals. Molecular haplotyping accomplishes direct phase determination by generation of hemizygous templates from diploid genomic samples. We report molecular haplotyping by allele-specific long-range PCR of two markers 9.5 kb apart at the CD4 locus: a bi-allelic Alu deletion and a multi-allelic repeat. We verified CD4 molecular haplotypes by classical Mendelian analysis. Molecular haplotyping should prove useful in mapping disease genes and in establishing founder effects.

Full Text

The Full Text of this article is available as a PDF (129K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Jorde LB. Linkage disequilibrium as a gene-mapping tool. Am J Hum Genet. 1995 Jan;56(1):11–14. [PMC free article] [PubMed]
  • Thomson G. Analysis of complex human genetic traits: an ordered-notation method and new tests for mode of inheritance. Am J Hum Genet. 1995 Aug;57(2):474–486. [PMC free article] [PubMed]
  • de la Chapelle A. Disease gene mapping in isolated human populations: the example of Finland. J Med Genet. 1993 Oct;30(10):857–865. [PMC free article] [PubMed]
  • Weber JL, May PE. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed]
  • Ruano G, Kidd KK, Stephens JC. Haplotype of multiple polymorphisms resolved by enzymatic amplification of single DNA molecules. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6296–6300. [PMC free article] [PubMed]
  • Ruano G, Kidd KK. Direct haplotyping of chromosomal segments from multiple heterozygotes via allele-specific PCR amplification. Nucleic Acids Res. 1989 Oct 25;17(20):8392–8392. [PMC free article] [PubMed]
  • Ruano G, Kidd KK. Genotyping and haplotyping of polymorphisms directly from genomic DNA via coupled amplification and sequencing (CAS). Nucleic Acids Res. 1991 Dec 25;19(24):6877–6882. [PMC free article] [PubMed]
  • Barnes WM. PCR amplification of up to 35-kb DNA with high fidelity and high yield from lambda bacteriophage templates. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2216–2220. [PMC free article] [PubMed]
  • Edwards MC, Gibbs RA. A human dimorphism resulting from loss of an Alu. Genomics. 1992 Nov;14(3):590–597. [PubMed]
  • Edwards MC, Clemens PR, Tristan M, Pizzuti A, Gibbs RA. Pentanucleotide repeat length polymorphism at the human CD4 locus. Nucleic Acids Res. 1991 Sep 11;19(17):4791–4791. [PMC free article] [PubMed]
  • Tishkoff SA, Dietzsch E, Speed W, Pakstis AJ, Kidd JR, Cheung K, Bonné-Tamir B, Santachiara-Benerecetti AS, Moral P, Krings M. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science. 1996 Mar 8;271(5254):1380–1387. [PubMed]
  • Päbo S, Higuchi RG, Wilson AC. Ancient DNA and the polymerase chain reaction. The emerging field of molecular archaeology. J Biol Chem. 1989 Jun 15;264(17):9709–9712. [PubMed]
  • Matera AG, Hellmann U, Schmid CW. A transpositionally and transcriptionally competent Alu subfamily. Mol Cell Biol. 1990 Oct;10(10):5424–5432. [PMC free article] [PubMed]
  • Neuhausen SL, Swensen J, Miki Y, Liu Q, Tavtigian S, Shattuck-Eidens D, Kamb A, Hobbs MR, Gingrich J, Shizuya H, et al. A P1-based physical map of the region from D17S776 to D17S78 containing the breast cancer susceptibility gene BRCA1. Hum Mol Genet. 1994 Nov;3(11):1919–1926. [PubMed]
  • Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med. 1995 Mar 16;332(11):706–711. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...