Linkage and association mapping of the LRP5 locus on chromosome 11q13 in type 1 diabetes

Linkage of chromosome 11q13 to type 1 diabetes (T1D) was first reported from genome scans (Davies et al. 1994; Hashimoto et al. 1994) resulting in P T. The disease association data, largely focused in the LRP5 region with 1,106 T1D families, provided no further evidence for disease association at LR...

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Published in:Human genetics 2003-07, Vol.113 (2), p.99-105
Main Authors: TWELLS, Rebecca C. J, MEIN, Charles A, RANCE, Helen E, CARR, Philippa, DUDBRIDGE, Frank, CORDELL, Heather J, COOPER, Jason, TUOMILEHTO-WOLF, Eva, TUOMILEHTO, Jaakko, PHILLIPS, Michael, METZKER, Michael, HESS, J. Fred, PAYNE, Felicity, TODD, John A, VEIJOLA, Riitta, GILBEY, Matthew, BRIGHT, Matthew, TIMMS, Andrew, NAKAGAWA, Yusuke, SNOOK, Hywel, NUTLAND, Sarah
Format: Article
Language:English
Subjects:
Biological and medical sciences
chromosome 11
Chromosome Mapping
Chromosomes, Human, Pair 11 - genetics
Diabetes Mellitus, Type 1 - genetics
Fundamental and applied biological sciences. Psychology
Genetic aspects
Genetic Linkage
Genomes
Genomics
Genotype
Humans
LDL-Receptor Related Proteins
lipoprotein (low-density) receptor-related protein
Low Density Lipoprotein Receptor-Related Protein-5
LRP5 gene
Microsatellite Repeats
Molecular and cellular biology
Receptors, LDL - genetics
Single nucleotide polymorphisms
Type 1 diabetes
Type 2 diabetes
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cited_by cdi_FETCH-LOGICAL-c447t-75ace105b8c8767ab6883545f41f056f8d45a1ade41ad1a520cb465bad9292b83
cites cdi_FETCH-LOGICAL-c447t-75ace105b8c8767ab6883545f41f056f8d45a1ade41ad1a520cb465bad9292b83
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container_start_page 99
container_title Human genetics
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creator TWELLS, Rebecca C. J
MEIN, Charles A
RANCE, Helen E
CARR, Philippa
DUDBRIDGE, Frank
CORDELL, Heather J
COOPER, Jason
TUOMILEHTO-WOLF, Eva
TUOMILEHTO, Jaakko
PHILLIPS, Michael
METZKER, Michael
HESS, J. Fred
PAYNE, Felicity
TODD, John A
VEIJOLA, Riitta
GILBEY, Matthew
BRIGHT, Matthew
TIMMS, Andrew
NAKAGAWA, Yusuke
SNOOK, Hywel
NUTLAND, Sarah
description Linkage of chromosome 11q13 to type 1 diabetes (T1D) was first reported from genome scans (Davies et al. 1994; Hashimoto et al. 1994) resulting in P T. The disease association data, largely focused in the LRP5 region with 1,106 T1D families, provided no further evidence for disease association at LRP5 or at D11S987. A second dataset, comprising 1,569 families from Finland, failed to replicate our previous findings at LRP5. The continued search for the variants of the putative IDDM4 locus will greatly benefit from the future development of a haplotype map of the genome.
doi_str_mv 10.1007/s00439-003-0940-6
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J ; MEIN, Charles A ; RANCE, Helen E ; CARR, Philippa ; DUDBRIDGE, Frank ; CORDELL, Heather J ; COOPER, Jason ; TUOMILEHTO-WOLF, Eva ; TUOMILEHTO, Jaakko ; PHILLIPS, Michael ; METZKER, Michael ; HESS, J. Fred ; PAYNE, Felicity ; TODD, John A ; VEIJOLA, Riitta ; GILBEY, Matthew ; BRIGHT, Matthew ; TIMMS, Andrew ; NAKAGAWA, Yusuke ; SNOOK, Hywel ; NUTLAND, Sarah</creator><creatorcontrib>TWELLS, Rebecca C. J ; MEIN, Charles A ; RANCE, Helen E ; CARR, Philippa ; DUDBRIDGE, Frank ; CORDELL, Heather J ; COOPER, Jason ; TUOMILEHTO-WOLF, Eva ; TUOMILEHTO, Jaakko ; PHILLIPS, Michael ; METZKER, Michael ; HESS, J. 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Association mapping under the linkage peak using 12 polymorphic microsatellite markers suggested some evidence of association with a two-marker haplotype, D11S1917*03-H0570POLYA*02, which was under-transmitted to affected siblings and over-transmitted to unaffected siblings ( P=1.5 x 10(-6)) (Nakagawa et al. 1998). Others have reported evidence for T1D association of the microsatellite marker D11S987, which is approximately 100 kb proximal to D11S1917 (Eckenrode et al. 2000). We have sequenced a 400-kb interval surrounding these loci and identified four genes, including the low-density lipoprotein receptor related protein (LRP5) gene, which has been considered as a functional candidate gene for T1D (Hey et al. 1998; Twells et al. 2001). Consequently, we have developed a comprehensive SNP map of the LRP5 gene region, and identified 95 SNPs encompassing 269 kb of genomic DNA, characterised the LD in the region and haplotypes (Twells et al. 2003). 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Here, we present our refined linkage curve of the IDDM4 region, comprising 32 microsatellite markers and 12 SNPs, providing a peak MLS=2.58, P=5 x 10(-4), at LRP5 g.17646G&gt;T. The disease association data, largely focused in the LRP5 region with 1,106 T1D families, provided no further evidence for disease association at LRP5 or at D11S987. A second dataset, comprising 1,569 families from Finland, failed to replicate our previous findings at LRP5. The continued search for the variants of the putative IDDM4 locus will greatly benefit from the future development of a haplotype map of the genome.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><cop>New York, NY</cop><pub>Springer</pub><pmid>12700977</pmid><doi>10.1007/s00439-003-0940-6</doi><tpages>7</tpages></addata></record>
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ispartof Human genetics, 2003-07, Vol.113 (2), p.99-105
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1432-1203
language eng
recordid cdi_proquest_miscellaneous_73372685
source Springer Nature
subjects Biological and medical sciences
chromosome 11
Chromosome Mapping
Chromosomes, Human, Pair 11 - genetics
Diabetes Mellitus, Type 1 - genetics
Fundamental and applied biological sciences. Psychology
Genetic aspects
Genetic Linkage
Genomes
Genomics
Genotype
Humans
LDL-Receptor Related Proteins
lipoprotein (low-density) receptor-related protein
Low Density Lipoprotein Receptor-Related Protein-5
LRP5 gene
Microsatellite Repeats
Molecular and cellular biology
Receptors, LDL - genetics
Single nucleotide polymorphisms
Type 1 diabetes
Type 2 diabetes
title Linkage and association mapping of the LRP5 locus on chromosome 11q13 in type 1 diabetes
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