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.
JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK. rebecca.twells@cimr.cam.ac.uk
Rebecca C J
RC
Twells
Charles A
CA
Mein
Michael S
MS
Phillips
J Fred
JF
Hess
Riitta
R
Veijola
Matthew
M
Gilbey
Matthew
M
Bright
Michael
M
Metzker
Benedicte A
BA
Lie
Amanda
A
Kingsnorth
Edward
E
Gregory
Yusuke
Y
Nakagawa
Hywel
H
Snook
William Y S
WY
Wang
Jennifer
J
Masters
Gillian
G
Johnson
Iain
I
Eaves
Joanna M M
JM
Howson
David
D
Clayton
Heather J
HJ
Cordell
Sarah
S
Nutland
Helen
H
Rance
Philippa
P
Carr
John A
JA
Todd
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