A map of the human genome in linkage disequilibrium units
A map of the human genome in linkage disequilibrium units
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 nonpseudoautosomal region of the X chromosome is subject to hemizygous selection; and (iii) at resolution less than ?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.
effective bottleneck time, hapmap, recombination, interference, selection
11835-11839
Tapper, W.
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Collins, A.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Gibson, J.
855033a6-38f3-4853-8f60-d7d4561226ae
Maniatis, N.
af642fc2-cf37-422e-921a-1990a8d4bcfd
Ennis, S.
7b57f188-9d91-4beb-b217-09856146f1e9
Morton, N.E.
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
2005
Tapper, W.
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Collins, A.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Gibson, J.
855033a6-38f3-4853-8f60-d7d4561226ae
Maniatis, N.
af642fc2-cf37-422e-921a-1990a8d4bcfd
Ennis, S.
7b57f188-9d91-4beb-b217-09856146f1e9
Morton, N.E.
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
Tapper, W., Collins, A., Gibson, J., Maniatis, N., Ennis, S. and Morton, N.E.
(2005)
A map of the human genome in linkage disequilibrium units.
Proceedings of the National Academy of Sciences of the United States of America, 102 (33), .
(doi:10.1073/pnas.0505262102).
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 nonpseudoautosomal region of the X chromosome is subject to hemizygous selection; and (iii) at resolution less than ?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.
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Published date: 2005
Additional Information:
Published online before print August 9, 2005
Keywords:
effective bottleneck time, hapmap, recombination, interference, selection
Organisations:
Human Genetics
Identifiers
Local EPrints ID: 24976
URI: http://eprints.soton.ac.uk/id/eprint/24976
ISSN: 0027-8424
PURE UUID: f90fb70a-ea6c-4113-960f-d3db3c659ff3
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Date deposited: 04 Apr 2006
Last modified: 16 Mar 2024 03:33
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Contributors
Author:
N. Maniatis
Author:
N.E. Morton
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