A Quantitative Trait Locus for Body Fat on Chromosome 1q43 in French Canadians: Linkage and Association Studies*

Obesity ◽  
2006 ◽  
Vol 14 (9) ◽  
pp. 1605-1615 ◽  
Author(s):  
Brahim Aissani ◽  
Louis Perusse ◽  
Gilles Lapointe ◽  
Yvon C. Chagnon ◽  
Luigi Bouchard ◽  
...  
2009 ◽  
Vol 38 (2) ◽  
pp. 226-232 ◽  
Author(s):  
Heike Vogel ◽  
Matthias Nestler ◽  
Franz Rüschendorf ◽  
Marcel-Dominique Block ◽  
Sina Tischer ◽  
...  

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.


2021 ◽  
Author(s):  
Alex N. Nguyen Ba ◽  
Katherine R. Lawrence ◽  
Artur Rego-Costa ◽  
Shreyas Gopalakrishnan ◽  
Daniel Temko ◽  
...  

Mapping the genetic basis of complex traits is critical to uncovering the biological mechanisms that underlie disease and other phenotypes. Genome-wide association studies (GWAS) in humans and quantitative trait locus (QTL) mapping in model organisms can now explain much of the observed heritability in many traits, allowing us to predict phenotype from genotype. However, constraints on power due to statistical confounders in large GWAS and smaller sample sizes in QTL studies still limit our ability to resolve numerous small-effect variants, map them to causal genes, identify pleiotropic effects across multiple traits, and infer non-additive interactions between loci (epistasis). Here, we introduce barcoded bulk quantitative trait locus (BB-QTL) mapping, which allows us to construct, genotype, and phenotype 100,000 offspring of a budding yeast cross, two orders of magnitude larger than the previous state of the art. We use this panel to map the genetic basis of eighteen complex traits, finding that the genetic architecture of these traits involves hundreds of small-effect loci densely spaced throughout the genome, many with widespread pleiotropic effects across multiple traits. Epistasis plays a central role, with thousands of interactions that provide insight into genetic networks. By dramatically increasing sample size, BB-QTL mapping demonstrates the potential of natural variants in high-powered QTL studies to reveal the highly polygenic, pleiotropic, and epistatic architecture of complex traits.Significance statementUnderstanding the genetic basis of important phenotypes is a central goal of genetics. However, the highly polygenic architectures of complex traits inferred by large-scale genome-wide association studies (GWAS) in humans stand in contrast to the results of quantitative trait locus (QTL) mapping studies in model organisms. Here, we use a barcoding approach to conduct QTL mapping in budding yeast at a scale two orders of magnitude larger than the previous state of the art. The resulting increase in power reveals the polygenic nature of complex traits in yeast, and offers insight into widespread patterns of pleiotropy and epistasis. Our data and analysis methods offer opportunities for future work in systems biology, and have implications for large-scale GWAS in human populations.


2020 ◽  
Vol 12 (4) ◽  
pp. 1632 ◽  
Author(s):  
Yusuff Oladosu ◽  
Mohd Y. Rafii ◽  
Fatai Arolu ◽  
Samuel Chibuike Chukwu ◽  
Ismaila Muhammad ◽  
...  

Flooding or submergence is one of the major environmental stressors affecting many man-made and natural ecosystems worldwide. The increase in the frequency and duration of heavy rainfall due to climate change has negatively affected plant growth and development, which eventually causes the death of plants if it persists for days. Most crops, especially rice, being a semi-aquatic plant, are greatly affected by flooding, leading to yield losses each year. Genetic variability in the plant response to flooding includes the quiescence scheme, which allows underwater endurance of a prolonged period, escape strategy through stem elongation, and alterations in plant architecture and metabolism. Investigating the mechanism for flooding survival in wild species and modern rice has yielded significant insight into developmental, physiological, and molecular strategies for submergence and waterlogging survival. Significant progress in the breeding of submergence tolerant rice varieties has been made during the last decade following the successful identification and mapping of a quantitative trait locus for submergence tolerance, designated as SUBMERGENCE 1 (SUB1) from the FR13A landrace. Using marker-assisted backcrossing, the SUB1 QTL (quantitative trait locus) has been incorporated into many elite varieties within a short time and with high precision as compared with conventional breeding methods. Despite the advancement in submergence tolerance, for future studies, there is a need for practical approaches exploring genome-wide association studies (GWA) and QTL in combination with specific tolerance traits, such as drought, salinity, disease and insect resistance.


2010 ◽  
Vol 42A (2) ◽  
pp. 153-161 ◽  
Author(s):  
K. Gopalakrishnan ◽  
J. Saikumar ◽  
C. G. Peters ◽  
S. Kumarasamy ◽  
P. Farms ◽  
...  

Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8 kb to <1.33 Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8 kb significantly lowered BP of the hypertensive S rat by 25 mmHg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8 kb congenic strain, which represents the shortest genomic segment to which a BP QTL has been mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Furthermore, a whole genome renal transcriptome analysis between S and the <81.8 kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation.


2015 ◽  
Vol 209 (3) ◽  
pp. 1067-1082 ◽  
Author(s):  
Qingzhang Du ◽  
Chenrui Gong ◽  
Qingshi Wang ◽  
Daling Zhou ◽  
Haijiao Yang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document