The University of Southampton
University of Southampton Institutional Repository

The impact of SNP density on fine-scale patterns of linkage disequilibrium

The impact of SNP density on fine-scale patterns of linkage disequilibrium
The impact of SNP density on fine-scale patterns of linkage disequilibrium
Linkage disequilibrium (LD) is a measure of the degree of association between alleles in a population. The detection of disease-causing variants by association with neighbouring single nucleotide polymorphisms (SNPs) depends on the existence of strong LD between them. Previous studies have indicated that the extent of LD is highly variable in different chromosome regions and different populations, demonstrating the importance of genome-wide accurate measurement of LD at high resolution throughout the human genome. A uniform feature of these studies has been the inability to detect LD in regions of low marker density. To investigate the dependence of LD patterns on marker selection we performed a high-resolution study in African-American, Asian and UK Caucasian populations. We selected over 5000 SNPs with an average spacing of 1 SNP per 2 kb after validating ca 12 000 SNPs derived from a dense SNP collection (1 SNP per 0.3 kb on average). Applications of different statistical methods of LD assessment highlight similar areas of high and low LD. However, at high resolution, features such as overall sequence coverage in LD blocks and block boundaries vary substantially with respect to marker density. Model-based linkage disequilibrium unit (LDU) maps appear robust to marker density and consistently influenced by marker allele frequency. The results suggest that very dense marker sets will be required to yield stable views of fine-scale LD in the human genome.
577-588
Ke, Xiayi
3d3489dc-c021-4669-bf5c-30c8733c1183
Hunt, Sarah
b4c58b2a-8111-4cf4-98f1-e099bfadb925
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Lawrence, Robert
f0cf51e5-7902-4355-ba98-d177c8b53d84
Stavrides, George
e177d412-e293-401e-bedd-cf9a38b969ba
Ghori, Jilur
e48fb936-b094-4a57-b541-a92b8f74441e
Whittaker, Pamela
af206de8-b90f-47b9-83a8-e5ce522b146f
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Morris, Andrew P.
055d1280-e160-496e-953f-3c9347fcd4d2
Bentley, David
a89fbf0f-05e9-4027-aac8-2482dec6cfb1
Cardon, Lon R.
509515ee-ded2-4097-9495-ce4dbfe9a2a2
Deloukas, Panos
f8c385df-85e0-4769-9a5b-aaf03ec01d1f
Ke, Xiayi
3d3489dc-c021-4669-bf5c-30c8733c1183
Hunt, Sarah
b4c58b2a-8111-4cf4-98f1-e099bfadb925
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Lawrence, Robert
f0cf51e5-7902-4355-ba98-d177c8b53d84
Stavrides, George
e177d412-e293-401e-bedd-cf9a38b969ba
Ghori, Jilur
e48fb936-b094-4a57-b541-a92b8f74441e
Whittaker, Pamela
af206de8-b90f-47b9-83a8-e5ce522b146f
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Morris, Andrew P.
055d1280-e160-496e-953f-3c9347fcd4d2
Bentley, David
a89fbf0f-05e9-4027-aac8-2482dec6cfb1
Cardon, Lon R.
509515ee-ded2-4097-9495-ce4dbfe9a2a2
Deloukas, Panos
f8c385df-85e0-4769-9a5b-aaf03ec01d1f

Ke, Xiayi, Hunt, Sarah, Tapper, William, Lawrence, Robert, Stavrides, George, Ghori, Jilur, Whittaker, Pamela, Collins, Andrew, Morris, Andrew P., Bentley, David, Cardon, Lon R. and Deloukas, Panos (2004) The impact of SNP density on fine-scale patterns of linkage disequilibrium. Human Molecular Genetics, 13 (6), 577-588. (doi:10.1093/hmg/ddh060).

Record type: Article

Abstract

Linkage disequilibrium (LD) is a measure of the degree of association between alleles in a population. The detection of disease-causing variants by association with neighbouring single nucleotide polymorphisms (SNPs) depends on the existence of strong LD between them. Previous studies have indicated that the extent of LD is highly variable in different chromosome regions and different populations, demonstrating the importance of genome-wide accurate measurement of LD at high resolution throughout the human genome. A uniform feature of these studies has been the inability to detect LD in regions of low marker density. To investigate the dependence of LD patterns on marker selection we performed a high-resolution study in African-American, Asian and UK Caucasian populations. We selected over 5000 SNPs with an average spacing of 1 SNP per 2 kb after validating ca 12 000 SNPs derived from a dense SNP collection (1 SNP per 0.3 kb on average). Applications of different statistical methods of LD assessment highlight similar areas of high and low LD. However, at high resolution, features such as overall sequence coverage in LD blocks and block boundaries vary substantially with respect to marker density. Model-based linkage disequilibrium unit (LDU) maps appear robust to marker density and consistently influenced by marker allele frequency. The results suggest that very dense marker sets will be required to yield stable views of fine-scale LD in the human genome.

This record has no associated files available for download.

More information

Published date: 15 March 2004

Identifiers

Local EPrints ID: 24804
URI: http://eprints.soton.ac.uk/id/eprint/24804
PURE UUID: b4a95a12-7ba8-4bb4-98e9-a2bfad7387e9
ORCID for William Tapper: ORCID iD orcid.org/0000-0002-5896-1889
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771

Catalogue record

Date deposited: 04 Apr 2006
Last modified: 16 Mar 2024 03:07

Export record

Altmetrics

Contributors

Author: Xiayi Ke
Author: Sarah Hunt
Author: William Tapper ORCID iD
Author: Robert Lawrence
Author: George Stavrides
Author: Jilur Ghori
Author: Pamela Whittaker
Author: Andrew Collins ORCID iD
Author: Andrew P. Morris
Author: David Bentley
Author: Lon R. Cardon
Author: Panos Deloukas

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×