scholarly journals Adrenal Gland Tumorigenesis after Gonadectomy in Mice Is a Complex Genetic Trait Driven by Epistatic Loci

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 651-661 ◽  
Author(s):  
Sophie Bernichtein ◽  
Enrico Petretto ◽  
Stacey Jamieson ◽  
Anuj Goel ◽  
Timothy J. Aitman ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Adrenal Gland ◽  
Quantitative Trait ◽  
Molecular Mechanisms ◽  
Inbred Mice ◽  
Direct Consequence ◽  
Suppressor Gene ◽  
Chromosome 8 ◽  
Genetic Trait ◽  
Trait Locus

Postgonadectomy adrenocortical tumorigenesis is a strain-specific phenomenon in inbred mice, assumed to be caused by elevated LH secretion and subsequent ectopic LH receptor (LHR) overexpression in adrenal gland. However, the molecular mechanisms of this cascade of events remain unknown. In this study, we took advantage of the mouse strain dependency of the phenotype to unravel its genetic basis. Our results present the first genome-wide screening related to this pathology in two independent F2 and backcross populations generated between the neoplastic DBA/2J and the nonsusceptible C57BL/6J strains. Surprisingly, the postgonadectomy elevation of serum LH was followed by similar up-regulation of adrenal LHR expression in both parental strains and their crosses, irrespective of their tumor status, indicating that it is not the immediate cause of the tumorigenesis. Linkage analysis revealed one major significant locus for the tumorigenesis on chromosome 8, modulated by epistasis with another quantitative trait locus on chromosome 18. Weight gain, a secondary phenotype after gonadectomy, showed a significant but separate quantitative trait locus on chromosome 7. Altogether, postgonadectomy adrenocortical tumorigenesis in DBA/2J mice is a dominant trait that is not a direct consequence of adrenal LHR expression but is driven by a complex genetic architecture. Analysis of candidate genes in the tumorigenesis linkage region showed that Sfrp1 (secreted frizzled-related protein 1), a tumor suppressor gene, is differentially expressed in the neoplastic areas. These findings may have relevance to the human pathogenesis of macronodular adrenal hyperplasia and adrenocortical tumors in postmenopausal women and why some of them develop obesity.

A quantitative trait locus for cold tolerance at the booting stage on rice chromosome 8

2007 ◽  
Vol 115 (5) ◽  
pp. 593-600 ◽  
Author(s):  
Makoto Kuroki ◽  
Koji Saito ◽  
Shuichi Matsuba ◽  
Narifumi Yokogami ◽  
Hiroyuki Shimizu ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Cold Tolerance ◽  
Quantitative Trait ◽  
Rice Chromosome ◽  
Chromosome 8 ◽  
Booting Stage ◽  
Trait Locus

Quantitative Trait Locus Mapping for Ethanol Teratogenesis in BXD Recombinant Inbred Mice

2012 ◽  
Vol 36 (8) ◽  
pp. 1340-1354 ◽  
Author(s):  
Chris Downing ◽  
Christina Balderrama-Durbin ◽  
Alexi Kimball ◽  
Jami Biers ◽  
Hali Wright ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Quantitative Trait Locus Mapping ◽  
Quantitative Trait ◽  
Recombinant Inbred ◽  
Inbred Mice ◽  
Recombinant Inbred Mice ◽  
Trait Locus ◽  
Locus Mapping

scholarly journals Role of genetics in peripheral arterial disease outcomes; significance of limb-salvage quantitative locus-1 genes

2017 ◽  
Vol 243 (2) ◽  
pp. 190-197 ◽  
Author(s):  
Emmanuel Okeke ◽  
Ayotunde O Dokun
Keyword(s):  
Quantitative Trait Locus ◽  
Limb Salvage ◽  
Disease Severity ◽  
Peripheral Artery Disease ◽  
Quantitative Trait ◽  
Molecular Mechanisms ◽  
Limb Ischemia ◽  
Peripheral Artery ◽  
Trait Locus ◽  
Artery Disease

Peripheral artery disease is a major health care problem with significant morbidity and mortality. Humans with peripheral artery disease exhibit two major and differential clinical manifestations – intermittent claudication and critical limb ischemia. Individuals with intermittent claudication or critical limb ischemia have overlapping risk factors and objective measures of blood flow. Hence, we hypothesized that variation in genetic make-up may be an important determinant in the severity of peripheral artery disease. Previous studies have identified polymorphism in genes, contributing to extent of atherosclerosis but much less is known about polymorphisms associated with genes that can influence peripheral artery disease severity. This review outlines some of the progress made up-to-date to unravel the molecular mechanisms underlining differential peripheral artery disease severity. By exploring the recovery phenotype of different mouse strains following experimental peripheral artery disease, our group identified the limb salvage-associated quantitative trait locus 1 on mouse chromosome 7 as the first genetic modifier of perfusion recovery and tissue necrosis phenotypes. Furthermore, a number of genes within LSq-1, such as ADAM12, IL-21Rα, and BAG3 were identified as genetic modifiers of peripheral artery disease severity that function through preservation of endothelial and skeletal muscle cells during ischemia. Taken together, these studies suggest manipulation of limb salvage-associated quantitative trait locus 1 genes show great promise as therapeutic targets in the management of peripheral artery disease. Impact statement Peripheral artery disease (PAD) is a major health care problem with significant morbidity and mortality. Individuals with similar atherosclerosis burden do display different severity of disease. This review outlines some of the progress made up-to-date in unraveling the molecular mechanisms underlining differential PAD severity with a focus on the role of the Limb Salvage-associated Quantitative trait locus 1 (LSq-1), a key locus in adaptation to ischemia in PAD.

Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice

1994 ◽  
Vol 32 (11-12) ◽  
pp. 397-407 ◽  
Author(s):  
Richard W. Hyman ◽  
Susan Frank ◽  
Craig H. Warden ◽  
Aaron Daluiski ◽  
Renu Heller ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Quantitative Trait Locus Analysis ◽  
Quantitative Trait ◽  
Recombinant Inbred ◽  
Inbred Mice ◽  
Recombinant Inbred Mice ◽  
Trait Locus

scholarly journals Genetic variation in the promoter of an R2R3−MYB transcription factor determines fruit malate content in apple (Malus domestica Borkh.)

2021 ◽  
Author(s):  
Dongjie Jia ◽  
Peng Wu ◽  
Fei Shen ◽  
Wei Li ◽  
Xiaodong Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Malus Domestica ◽  
Quantitative Trait ◽  
Molecular Mechanisms ◽  
Chromosome 8 ◽  
Myb Transcription Factor ◽  
Nucleotide Polymorphisms ◽  
Malus Domestica Borkh ◽  
Trait Locus ◽  
R2r3 Myb

Abstract Deciphering the mechanism of malate accumulation in apple (Malus domestica Borkh.) fruits can help to improve their flavor quality and enhance their benefits for human health. Here, we analyzed malate content as a quantitative trait that is determined mainly by genetic effects. In a previous study, we identified an R2R3−MYB transcription factor named MdMYB44 that was a candidate gene in qtl08.1 (quantitative trait locus mapped to chromosome 8) of fruit malate content. In the present study, we established that MdMYB44 negatively regulates fruit malate accumulation by repressing the promoter activity of the malate-associated genes Ma1 (Al-Activated Malate Transporter 9), Ma10 (P-type ATPase 10), MdVHA-A3 (V-type ATPase A3), and MdVHA-D2 (V-type ATPase D2). Two single-nucleotide polymorphisms (SNPs) in the MdMYB44 promoter, SNP A/G and SNP T/−, were experimentally shown to associate with fruit malate content. The TATA-box in the MdMYB44 promoter in the presence of SNP A enhances the basal activity of the MdMYB44 promoter. The binding of a basic-helix–loop–helix transcription factor MdbHLH49 to the MdMYB44 promoter was enhanced by the presence of SNP T, leading to increased MdMYB44 transcript levels and reduced malate accumulation. Furthermore, MdbHLH49 interacts with MdMYB44 and enhances MdMYB44 activity. The two SNPs could be used in combination to select for sour or non-sour apples, providing a valuable tool for the selection of fruit acidity by the apple breeding industry. This research is important for understanding the complex molecular mechanisms of fruit malate accumulation and accelerating the development of germplasm innovation in apple species and cultivars.

scholarly journals Quantitative trait locus mapping of airway responsiveness to chromosomes 6 and 7 in inbred mice

1999 ◽  
Vol 277 (6) ◽  
pp. L1118-L1123 ◽  
Author(s):  
G. T. De Sanctis ◽  
J. B. Singer ◽  
A. Jiao ◽  
C. N. Yandava ◽  
Y. H. Lee ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Qtl Mapping ◽  
Quantitative Trait ◽  
Genetic Factors ◽  
Inbred Mice ◽  
Airway Responsiveness ◽  
Chromosome 17 ◽  
Chromosome 6 ◽  
Trait Locus ◽  
Locus Mapping

Quantitative trait locus (QTL) mapping was used to identify chromosomal regions contributing to airway hyperresponsiveness in mice. Airway responsiveness to methacholine was measured in A/J and C3H/HeJ parental strains as well as in progeny derived from crosses between these strains. QTL mapping of backcross [(A/J × C3H/HeJ) × C3H/HeJ] progeny ( n = 137–227 informative mice for markers tested) revealed two significant linkages to loci on chromosomes 6 and 7. The QTL on chromosome 6 confirms the previous report by others of a linkage in this region in the same genetic backgrounds; the second QTL, on chromosome 7, represents a novel locus. In addition, we obtained suggestive evidence for linkage (logarithm of odds ratio = 1.7) on chromosome 17, which lies in the same region previously identified in a cross between A/J and C57BL/6J mice. Airway responsiveness in a cross between A/J and C3H/HeJ mice is under the control of at least two major genetic loci, with evidence for a third locus that has been previously implicated in an A/J and C57BL/6J cross; this indicates that multiple genetic factors control the expression of this phenotype.

scholarly journals Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice

2004 ◽  
Vol 17 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Malcolm A. Lyons ◽  
Henning Wittenburg ◽  
Renhua Li ◽  
Kenneth A. Walsh ◽  
Ron Korstanje ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Experimental Design ◽  
Qtl Analysis ◽  
Quantitative Trait ◽  
Inbred Mice ◽  
Hdl Cholesterol ◽  
Common Variants ◽  
Genetic Determinants ◽  
Cholesterol Levels ◽  
Trait Locus

To identify genetic determinants of lipoprotein levels, we are performing quantitative trait locus (QTL) analysis on a series of mouse intercrosses in a “daisy chain” experimental design, to increase the power of detecting QTL and to identify common variants that should segregate in multiple intercrosses. In this study, we intercrossed strains CAST/Ei and 129S1/SvImJ, determined HDL, total, and non-HDL cholesterol levels, and performed QTL mapping using Pseudomarker software. For HDL cholesterol, we identified two significant QTL on chromosome (Chr) 1 ( Hdlq5, 82 cM, 60–100 cM) and Chr 4 ( Hdlq10, 20 cM, 10–30 cM). For total cholesterol, we identified three significant QTL on Chr 1 ( Chol7, 74 cM, 65–80 cM), Chr 4 ( Chol8, 12 cM, 0–30 cM), and Chr 17 ( Chol9, 54 cM, 20–60 cM). For non-HDL cholesterol, we identified significant QTL on Chr 8 ( Nhdlq1, 34 cM, 20–60 cM) and Chr X ( Nhdlq2, 6 cM, 0–18 cM). Hdlq10 was the only QTL detected in two intercrosses involving strain CAST/Ei. Hdlq5, Hdlq10, Nhdlq1, and two suggestive QTL at D7Mit246 and D15Mit115 coincided with orthologous human lipoprotein QTL. Our analysis furthers the knowledge of the genetic control of lipoprotein levels and points to the importance of Hdlq10, which was detected repeatedly in multiple studies.

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