Archiver > GENEALOGY-DNA > 2005-03 > 1112017694

From: "Steven C. Perkins" <>
Subject: TAQ snps
Date: Mon, 28 Mar 2005 07:48:41 -0600

This article discusses TAQ snps:

A High-Resolution Linkage-Disequilibrium Map of the Human Major
Histocompatibility Complex and First Generation of Tag Single-Nucleotide

Marcos M. Miretti,1 Emily C. Walsh,2 Xiayi Ke,3 Marcos Delgado,1 Mark
Griffiths,1 Sarah Hunt,1 Jonathan Morrison,1 Pamela Whittaker,1 Eric S.
Lander,2 Lon R. Cardon,3 David R. Bentley,1 John D. Rioux,2 Stephan
Beck,1 and Panos Deloukas1

1Wellcome Trust Sanger Institute, Hinxton, United Kingdom; 2Broad
Institute of Massachusetts Institute of Technology and Harvard,
Cambridge, MA; and 3Wellcome Trust Centre for Human Genetics, University
of Oxford, Oxford, United Kingdom

Received December 3, 2004; accepted for publication February 2, 2005;
electronically published March 1, 2005.

Autoimmune, inflammatory, and infectious diseases present a major burden
to human health and are frequently associated with loci in the human
major histocompatibility complex (MHC). Here, we report a high-resolution
(1.9 kb) linkage-disequilibrium (LD) map of a 4.46-Mb fragment containing
the MHC in U.S. pedigrees with northern and western European ancestry
collected by the Centre d'Etude du Polymorphisme Humain (CEPH) and the
first generation of haplotype tag single-nucleotide polymorphisms
(tagSNPs) that provide up to a fivefold increase in genotyping efficiency
for all future MHC-linked disease-association studies. The data confirm
previously identified recombination hotspots in the class II region and
allow the prediction of numerous novel hotspots in the class I and class
III regions. The region of longest LD maps outside the classic MHC to the
extended class I region spanning the MHC-linked olfactory-receptor gene
cluster. The extended haplotype homozygosity analysis for recent positive
selection shows that all 14 outlying haplotype variants map to a single
extended haplotype, which most commonly bears HLA-DRB1*1501. The SNP
data, haplotype blocks, and tagSNPs analysis reported here have been
entered into a multidimensional Web-based database (GLOVAR), where they
can be accessed and viewed in the context of relevant genome annotation.
This LD map allowed us to give coordinates for the extremely variable LD
structure underlying the MHC.


Steven C. Perkins

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