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
-
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
-
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
-
Human recombination hot spots hidden in regions of strong marker association.
Nat Genet. 2005 Jun;37(6):601-6
PMID: 15880103
-
The X chromosome and the rate of deleterious mutations in humans.
Am J Hum Genet. 2000 Aug;67(2):515-7
PMID: 10882570
-
Hardy-Weinberg quality control.
Ann Hum Genet. 1999 Nov;63(Pt 6):535-8
PMID: 11246455
-
The optimal measure of allelic association.
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5217-21
PMID: 11309498
-
Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex.
Nat Genet. 2001 Oct;29(2):217-22
PMID: 11586303
-
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
-
Crossover interference in the mouse.
Genetics. 2002 Mar;160(3):1123-31
PMID: 11901128
-
A high-resolution recombination map of the human genome.
Nat Genet. 2002 Jul;31(3):241-7
PMID: 12053178
-
A first-generation linkage disequilibrium map of human chromosome 22.
Nature. 2002 Aug 1;418(6897):544-8
PMID: 12110843
-
Detecting recent positive selection in the human genome from haplotype structure.
Nature. 2002 Oct 24;419(6909):832-7
PMID: 12397357
-
Linkage disequilibrium in human populations.
Proc Natl Acad Sci U S A. 2003 May 13;100(10):6069-74
PMID: 12721363
-
A metric linkage disequilibrium map of a human chromosome.
Ann Hum Genet. 2003 Nov;67(Pt 6):487-94
PMID: 14641236
-
The International HapMap Project.
Nature. 2003 Dec 18;426(6968):789-96
PMID: 14685227
-
Positional cloning by linkage disequilibrium.
Am J Hum Genet. 2004 May;74(5):846-55
PMID: 15048619
-
The fine-scale structure of recombination rate variation in the human genome.
Science. 2004 Apr 23;304(5670):581-4
PMID: 15105499
-
Estimates of the genomic mutation rate for detrimental alleles in Drosophila melanogaster.
Genetics. 2004 Jun;167(2):815-26
PMID: 15238530
-
A combined linkage-physical map of the human genome.
Am J Hum Genet. 2004 Dec;75(6):1143-8
PMID: 15486828
-
Estimation of linkage disequilibrium in randomly mating populations.
Heredity (Edinb). 1974 Oct;33(2):229-39
PMID: 4531429
-
A mapping function for man.
Hum Hered. 1977;27(2):99-104
PMID: 863463
-
Is the most frequent allele the oldest?
Theor Popul Biol. 1977 Apr;11(2):141-60
PMID: 867285
-
Disequilibrium mapping: composite likelihood for pairwise disequilibrium.
Genomics. 1996 Aug 15;36(1):1-16
PMID: 8812410
-
Linkage map integration.
Genomics. 1996 Aug 15;36(1):157-62
PMID: 8812427
-
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
-
Mapping a disease locus by allelic association.
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1741-5
PMID: 9465087
-
Cosmopolitan linkage disequilibrium maps.
Hum Genomics. 2005 Mar;2(1):20-7
PMID: 15814065