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PMID: 16091463 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A map of the human genome in linkage disequilibrium units.

Tapper W, Collins A, Gibson J, Maniatis N, Ennis S, Morton NE

Abstract

Two genetic maps with additive distances contribute information about recombination patterns, recombinogenic sequences, and discovery of genes affecting a particular phenotype. Recombination is measured in morgans (w) over a single generation in a linkage map but may cover thousands of generations in a linkage disequilibrium (LD) map measured in LD units (LDU). We used a subset of single nucleotide polymorphisms from the HapMap Project to create a genome-wide map in LDU. Recombination accounts for 96.8% of the LDU variance in chromosome arms and 92.4% in their deciles. However, deeper analysis shows that LDU/w, an estimate of the effective bottleneck time (t), is significantly variable among chromosome arms because (i) the linkage map is approximated from the Haldane function, then adjusted toward the Kosambi function that is more accurate but still exaggerates w for all chromosomes, especially shorter ones; (ii) the non-pseudoautosomal region of the X chromosome is subject to hemizygous selection; and (iii) at resolution less than approximately 40,000 markers per w, there are indeterminacies (holes) in the LD map reflecting intervals of very high recombination. Selection and stochastic variation in small regions must have effects, which remain to be investigated by comparisons among populations. These considerations suggest an optimal strategy to eliminate holes quickly, greatly enhance the resolution of sex-specific linkage maps, and maximize the gain in association mapping by using LD maps.

MeSH Terms
Chromosome Mapping Chromosomes, Human, Pair 19/genetics Female Genome, Human Humans Linkage Disequilibrium/genetics Male Polymorphism, Single Nucleotide/genetics Recombination, Genetic/genetics Selection, Genetic Sex Characteristics Time Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Tapper W
Human Genetics Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, United Kingdom.
Collins A
Gibson J
Maniatis N
Ennis S
Morton N E
References (27)
27 references, click to expand
  1. Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps.
    Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18075-80 PMID: 15604137
  2. The optimal measure of linkage disequilibrium reduces error in association mapping of affection status.
    Hum Mol Genet. 2005 Jan 1;14(1):145-53 PMID: 15548543
  3. Human recombination hot spots hidden in regions of strong marker association.
    Nat Genet. 2005 Jun;37(6):601-6 PMID: 15880103
  4. The X chromosome and the rate of deleterious mutations in humans.
    Am J Hum Genet. 2000 Aug;67(2):515-7 PMID: 10882570
  5. Hardy-Weinberg quality control.
    Ann Hum Genet. 1999 Nov;63(Pt 6):535-8 PMID: 11246455
  6. The optimal measure of allelic association.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5217-21 PMID: 11309498
  7. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex.
    Nat Genet. 2001 Oct;29(2):217-22 PMID: 11586303
  8. The first linkage disequilibrium (LD) maps: delineation of hot and cold blocks by diplotype analysis.
    Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2228-33 PMID: 11842208
  9. Crossover interference in the mouse.
    Genetics. 2002 Mar;160(3):1123-31 PMID: 11901128
  10. A high-resolution recombination map of the human genome.
    Nat Genet. 2002 Jul;31(3):241-7 PMID: 12053178
  11. A first-generation linkage disequilibrium map of human chromosome 22.
    Nature. 2002 Aug 1;418(6897):544-8 PMID: 12110843
  12. Detecting recent positive selection in the human genome from haplotype structure.
    Nature. 2002 Oct 24;419(6909):832-7 PMID: 12397357
  13. Linkage disequilibrium in human populations.
    Proc Natl Acad Sci U S A. 2003 May 13;100(10):6069-74 PMID: 12721363
  14. A metric linkage disequilibrium map of a human chromosome.
    Ann Hum Genet. 2003 Nov;67(Pt 6):487-94 PMID: 14641236
  15. The International HapMap Project.
    Nature. 2003 Dec 18;426(6968):789-96 PMID: 14685227
  16. Positional cloning by linkage disequilibrium.
    Am J Hum Genet. 2004 May;74(5):846-55 PMID: 15048619
  17. The fine-scale structure of recombination rate variation in the human genome.
    Science. 2004 Apr 23;304(5670):581-4 PMID: 15105499
  18. Estimates of the genomic mutation rate for detrimental alleles in Drosophila melanogaster.
    Genetics. 2004 Jun;167(2):815-26 PMID: 15238530
  19. A combined linkage-physical map of the human genome.
    Am J Hum Genet. 2004 Dec;75(6):1143-8 PMID: 15486828
  20. Estimation of linkage disequilibrium in randomly mating populations.
    Heredity (Edinb). 1974 Oct;33(2):229-39 PMID: 4531429
  21. A mapping function for man.
    Hum Hered. 1977;27(2):99-104 PMID: 863463
  22. Is the most frequent allele the oldest?
    Theor Popul Biol. 1977 Apr;11(2):141-60 PMID: 867285
  23. Disequilibrium mapping: composite likelihood for pairwise disequilibrium.
    Genomics. 1996 Aug 15;36(1):1-16 PMID: 8812410
  24. Linkage map integration.
    Genomics. 1996 Aug 15;36(1):157-62 PMID: 8812427
  25. A metric map of humans: 23,500 loci in 850 bands.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14771-5 PMID: 8962130
  26. Mapping a disease locus by allelic association.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1741-5 PMID: 9465087
  27. Cosmopolitan linkage disequilibrium maps.
    Hum Genomics. 2005 Mar;2(1):20-7 PMID: 15814065
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2005-08-16
Epub
2005-00-09
Pages
11835-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1188000
Subset
IM
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