Congenic strain confirms putative quantitative trait locus for body weight in the rat

Linkage studies suggested that a quantitative trait locus (QTL) for blood pressure (BP) was present in a region on chromosome 17 (Chr 17) of Dahl salt-sensitive (DSS) rats. A subsequent congenic strain targeting this QTL, however, could not confirm it. These conflicting results called into question the validity of localization of a QTL by linkage followed by the use of a congenic strain made with an incomplete chromosome coverage. To resolve this issue, we constructed five new congenic strains, designated C17S.L1 to C17S.L5, that completely spanned the ±2 LOD confidence interval supposedly containing the QTL. Each congenic strain was made by replacing a segment of the DSS rat by that of the normotensive Lewis (LEW) rat. The only section to be LL homozygous is the region on Chr 17 specified in a congenic strain, as evidenced by a total genome scan. The results showed that BPs of C17S.L1 and C17S.L2 were lower ( P < 0.04) than that of DSS rats. In contrast, BPs of C17S.L3, C17S.L4, and C17S.L5 were not different ( P > 0.6) from that of DSS rats. Consequently, a BP QTL must be located in an interval of ∼15 cM shared between C17S.L1 and C17S.L2 and unique to them both, as opposed to C17S.L3, C17S.L4, and C17S.L5. The present study illustrates the importance of thorough chromosome coverage, the necessity for a genome-wide screening, and the use of “negative” controls in physically mapping a QTL by congenic strains.

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Quantitative trait locus for body weight identified on rat chromosome 4 in inbred alcohol-preferring and -nonpreferring rats: Potential implications for neuropeptide Y and corticotrophin releasing hormone 2

Alcohol ◽

10.1016/j.alcohol.2012.10.005 ◽

2013 ◽

Vol 47 (1) ◽

pp. 63-67 ◽

Cited By ~ 3

Author(s):

John Paul Spence ◽

Dongbing Lai ◽

Anantha Shekhar ◽

Lucinda G. Carr ◽

Tatiana Foroud ◽

...

Keyword(s):

Quantitative Trait Locus ◽

Body Weight ◽

Neuropeptide Y ◽

Quantitative Trait ◽

Chromosome 4 ◽

Releasing Hormone ◽

Trait Locus

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Two closely linked interactive blood pressure QTL on rat chromosome 5 defined using congenic Dahl rats

Physiological Genomics ◽

10.1152/physiolgenomics.00080.2001 ◽

2002 ◽

Vol 8 (2) ◽

pp. 81-86 ◽

Cited By ~ 38

Author(s):

Michael R. Garrett ◽

John P. Rapp

Keyword(s):

Blood Pressure ◽

Quantitative Trait Locus ◽

Quantitative Trait ◽

Congenic Strain ◽

Major Effect ◽

Large Region ◽

Chromosome 5 ◽

Low Blood Pressure ◽

Trait Locus

Previously we reported the construction of a congenic strain, S.LEW( 5 ), spanning a large region of rat chromosome 5. The Lewis (LEW) strain was the donor, and the Dahl salt-sensitive (S) strain was the recipient. The congenic strain included a blood pressure quantitative trait locus (QTL). In the present work, a series of nine congenic substrains were constructed from S.LEW( 5 ) which defined two closely linked blood pressure QTL in the region previously thought to contain only one. LEW low-blood-pressure alleles at both QTL were required for a major effect on blood pressure. Neither LEW allele alone had a significant effect on blood pressure. The two QTL were localized to regions 6.3 and 4.6 cM, and these were 1.0 cM apart.

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Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1

Physiological Genomics ◽

10.1152/physiolgenomics.00011.2009 ◽

2009 ◽

Vol 38 (2) ◽

pp. 226-232 ◽

Cited By ~ 23

Author(s):

Heike Vogel ◽

Matthias Nestler ◽

Franz Rüschendorf ◽

Marcel-Dominique Block ◽

Sina Tischer ◽

...

Keyword(s):

Quantitative Trait Locus ◽

Body Weight ◽

Body Fat ◽

Quantitative Trait ◽

Plasma Cholesterol ◽

Chromosome 1 ◽

Nzo Mice ◽

Distal Chromosome ◽

Trait Locus ◽

Haplotype Mapping

New Zealand obese (NZO) mice present a metabolic syndrome of obesity, insulin resistance, and diabetes. To identify chromosomal segments associated with these traits, we intercrossed NZO mice with the lean and diabetes-resistant C57BL/6J (B6) strain. Obesity and hyperglycemia in the (NZO×B6)F2 intercross population were predominantly due to a broad quantitative trait locus (QTL) on chromosome 1 ( Nob3; logarithm of the odds score 16.1, 16.0, 4.0 for body weight, body fat, and blood glucose, respectively), producing a difference between genotypes of 12.7 or 5.2 g of body weight and 12.0 or 4.0 g of body fat in females or males, respectively. In addition, significant QTL on chromosomes 3 and 13 and suggestive QTL on chromosomes 4, 6, 9, 12, 14, and 19 contributed to the obese phenotype. Distal chromosome 5 was significantly linked with plasma cholesterol (LOD score 10.7). Introgression of two segments of Nob3 into B6 confirmed the adipogenic effect of the QTL and suggested the presence of at least one causal gene. Haplotype mapping reduced the critical region of the distal part of the QTL to 31 Mbp containing the potential candidates Nr1i3, Apoa2, Atp1a2, Prox1, and Hsd11b1. We conclude that obesity and hyperglycemia of NZO is to a large part caused by variant genes located in Nob3 on chromosome 1. Since these exert robust effects on a B6 background, the QTL Nob3 is a prime target for identification of a novel diabesity gene.

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