Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene.
Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype diversity in "LD blocks," interspersed by apparent "hot spots" of recombination. Previously, we cloned and physically characterized the low-density lipoprotein-receptor-related protein 5 (LRP5) gene. Here, we have extensively analysed both LRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5, including a hot-spot region from intron 1 to intron 7 of LRP5, where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. For LRP5, three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination.
Twells
Rebecca C J
RC
JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK. rebecca.twells@cimr.cam.ac.uk
Mein
Charles A
CA
Phillips
Michael S
MS
Hess
J Fred
JF
Veijola
Riitta
R
Gilbey
Matthew
M
Bright
Matthew
M
Metzker
Michael
M
Lie
Benedicte A
BA
Kingsnorth
Amanda
A
Gregory
Edward
E
Nakagawa
Yusuke
Y
Snook
Hywel
H
Wang
William Y S
WY
Masters
Jennifer
J
Johnson
Gillian
G
Eaves
Iain
I
Howson
Joanna M M
JM
Clayton
David
D
Cordell
Heather J
HJ
Nutland
Sarah
S
Rance
Helen
H
Carr
Philippa
P
Todd
John A
JA
D024509:3' Flanking Region / Q000235:genetics; D024506:5' Flanking Region / Q000235:genetics; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D026502:LDL-Receptor Related Proteins; D015810:Linkage Disequilibrium / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D018895:Microsatellite Repeats / Q000235:genetics; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*
D005819:Genetic Markers; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D011973:Receptors, LDL