Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations.
BACKGROUND
An understanding of linkage disequilibrium (LD) structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing (WGS) provides the opportunity to determine LD structures at maximal resolution.


RESULTS
We compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations. WGS provides up to 5.7-fold greater SNP density than array-based data and achieves much greater resolution of LD structure, allowing for identification of up to 2.8-fold more regions of intense recombination. The absence of ascertainment bias in variant genotyping improves the population representativeness of the WGS maps, and highlights the extent of uncaptured variation using array genotyping methodologies. The complete capture of LD patterns using WGS allows for higher genome-wide association study (GWAS) power compared to array-based GWAS, with WGS also allowing for the analysis of rare variation. The impact of marker ascertainment issues in arrays has been greatest for Sub-Saharan African populations where larger sample sizes and substantially higher marker densities are required to fully resolve the LD structure.


CONCLUSIONS
WGS provides the best possible resource for LD mapping due to the maximal marker density and lack of ascertainment bias. WGS LD maps provide a rich resource for medical and population genetics studies. The increasing availability of WGS data for large populations will allow for improved research utilising LD, such as GWAS and recombination biology studies.
Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (MP 808), Tremona Road, Southampton, SO16 6YD, UK. r.j.pengelly@soton.ac.uk.
Reuben J
RJ
Pengelly
Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (MP 808), Tremona Road, Southampton, SO16 6YD, UK. w.j.tapper@soton.ac.uk.
William
W
Tapper
Centre for Biological Sciences, Faculty of Natural & Environmental Sciences, University of Southampton, Southampton, UK. j.gibson@soton.ac.uk.
Jane
J
Gibson
Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (MP 808), Tremona Road, Southampton, SO16 6YD, UK. m.knut@soton.ac.uk.
Marcin
M
Knut
Complete Genomics, Inc., Mountain View, CA, USA. rtearle@completegenomics.com.
Rick
R
Tearle
Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (MP 808), Tremona Road, Southampton, SO16 6YD, UK. a.r.collins@soton.ac.uk.
Andrew
A
Collins
Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (MP 808), Tremona Road, Southampton, SO16 6YD, UK. s.ennis@soton.ac.uk.
Sarah
S
Ennis
D001483:Base Sequence; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers; D005828:Genetics, Population; D015894:Genome, Human; D060005:Genotyping Techniques; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D020161:Physical Chromosome Mapping; D018401:Sample Size
D005819:Genetic Markers