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High-resolution QTL Analysis Reveals Multiple Diabetes Susceptibility Loci Mapped to Intervals less than 800-kb in the Species Conserved Niddm1i of the GK Rat.

Granhall, Charlotte LU ; Park, Hee-Bok LU ; Fakhrai-Rad, Hossein and Luthman, Holger LU (2006) In Genetics 174(Sep 1). p.1565-1572
Abstract
Niddmli, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat, causes impaired glucose tolerance in the congenic NIDDM11 strain. Niddm1i is homologous to both human and mouse regions linked with type 2 diabetes susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected for one recombination event within Niddm1i combined with characterization of subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb (Niddmli4, P = 5 X 10(-6)). Two adjacent loci were also detected, and the GK allele at Niddn1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose-lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb) affecting body weight was identified.... (More)
Niddmli, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat, causes impaired glucose tolerance in the congenic NIDDM11 strain. Niddm1i is homologous to both human and mouse regions linked with type 2 diabetes susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected for one recombination event within Niddm1i combined with characterization of subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb (Niddmli4, P = 5 X 10(-6)). Two adjacent loci were also detected, and the GK allele at Niddn1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose-lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb) affecting body weight was identified. Experimental data from subcongenics supported the four loci. Sorcs1, one of the two known diabetes susceptibility genes in the region, resides within Niddm1i3, while TJ712 maps outside all four loci. Multiple-marker QTL analysis incorporating the effect of cosegregating QTL as cofactors together with genetically selected progeny can remarkably enhance resolution of QTL. The data demonstrate that the species-conserved Niddm1i is a composite of at least four QTL affecting type 2 diabetes susceptibility and that two adjacent QTL (Niddm1i2(GK) and Niddm1i3(GK)) act in opposite directions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genetics
volume
174
issue
Sep 1
pages
1565 - 1572
publisher
Genetics Society of America
external identifiers
  • wos:000242532600042
  • scopus:33751339484
ISSN
0016-6731
DOI
10.1534/genetics.106.062208
language
English
LU publication?
yes
id
76debf04-52e7-4943-8bc6-acd082e69658 (old id 161262)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16951059&dopt=Abstract
date added to LUP
2016-04-01 11:40:49
date last changed
2020-01-12 08:23:34
@article{76debf04-52e7-4943-8bc6-acd082e69658,
  abstract     = {Niddmli, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat, causes impaired glucose tolerance in the congenic NIDDM11 strain. Niddm1i is homologous to both human and mouse regions linked with type 2 diabetes susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected for one recombination event within Niddm1i combined with characterization of subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb (Niddmli4, P = 5 X 10(-6)). Two adjacent loci were also detected, and the GK allele at Niddn1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose-lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb) affecting body weight was identified. Experimental data from subcongenics supported the four loci. Sorcs1, one of the two known diabetes susceptibility genes in the region, resides within Niddm1i3, while TJ712 maps outside all four loci. Multiple-marker QTL analysis incorporating the effect of cosegregating QTL as cofactors together with genetically selected progeny can remarkably enhance resolution of QTL. The data demonstrate that the species-conserved Niddm1i is a composite of at least four QTL affecting type 2 diabetes susceptibility and that two adjacent QTL (Niddm1i2(GK) and Niddm1i3(GK)) act in opposite directions.},
  author       = {Granhall, Charlotte and Park, Hee-Bok and Fakhrai-Rad, Hossein and Luthman, Holger},
  issn         = {0016-6731},
  language     = {eng},
  number       = {Sep 1},
  pages        = {1565--1572},
  publisher    = {Genetics Society of America},
  series       = {Genetics},
  title        = {High-resolution QTL Analysis Reveals Multiple Diabetes Susceptibility Loci Mapped to Intervals less than 800-kb in the Species Conserved Niddm1i of the GK Rat.},
  url          = {http://dx.doi.org/10.1534/genetics.106.062208},
  doi          = {10.1534/genetics.106.062208},
  volume       = {174},
  year         = {2006},
}