A major suppressor of cell death, slm1, modifies the expression of the maize (Zea mays L.) lesion mimic mutation les23

Genome ◽  
2004 ◽  
Vol 47 (5) ◽  
pp. 961-969 ◽  
Author(s):  
Bryan W Penning ◽  
Gurmukh S Johal ◽  
Michael D McMullen
Keyword(s):  
Cell Death ◽  
Quantitative Trait ◽  
Chromosome 2 ◽  
Genetic Modifiers ◽  
Lesion Mimic ◽  
Cell Death Pathway ◽  
Delayed Initiation ◽  
Significant Locus ◽  
Trait Locus ◽  
Lesion Severity

Disease lesion mimics provide an excellent biological system to study the genetic basis of cell death in plants. Many lesion mimics show variation in phenotype expression in different genetic backgrounds. Our goal was to identify quantitative trait loci (QTL) modifying lesion mimic expression thereby identifying genetic modifiers of cell death. A recessive lesion mimic, les23, in a severe-expressing line was crossed to the maize inbred line Mo20W, a lesion-suppressing line, and an F2 population was developed for QTL analysis. In addition to locating les23 to the short arm of chromosome 2, this analysis detected significant loci for modification of lesion expression. One highly significant locus was found on the long arm of chromosome 2. The Mo20W allele at this QTL significantly delayed initiation of the lesion phenotype and decreased the final lesion severity. Other QTL with lesser effect affected severity of lesion expression without affecting lesion initiation date. Our results demonstrate that dramatic change in lesion phenotype can be controlled by a single major QTL. The presumed function of this QTL in normal plants is to regulate some aspect of the cell death pathway underlying the les23 phenotype.Key words: genetic background, quantitative trait locus, phenotype suppression, Mo20W, corn.

A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2

1997 ◽  
Vol 15 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Anthony G. Comuzzie ◽  
James E. Hixson ◽  
Laura Almasy ◽  
Braxton D. Mitchell ◽  
Michael C. Mahaney ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Human Chromosome ◽  
Fat Mass ◽  
Quantitative Trait ◽  
Major Quantitative Trait Locus ◽  
Chromosome 2 ◽  
Serum Leptin ◽  
Trait Locus

scholarly journals Gpr63 is a novel modifier of microcephaly in Ttc21b mouse mutants

2018 ◽  
Author(s):  
J. Snedeker ◽  
WJ Gibbons ◽  
D.R. Prows ◽  
R.W. Stottmann
Keyword(s):  
Quantitative Trait ◽  
Genetic Background ◽  
Chromosome 6 ◽  
Chromosome 4 ◽  
Genetic Modifiers ◽  
Causal Gene ◽  
Mouse Mutants ◽  
Signaling Center ◽  
Trait Locus ◽  
G Protein Coupled

ABSTRACTThe primary cilium is a critical signaling center for proper embryonic development. Previous studies have demonstrated that mice lacking Ttc21b have impaired retrograde trafficking within the cilium and multiple organogenesis phenotypes, including microcephaly. Interestingly, the severity of the microcephaly in Ttc21baln/aln homozygous null mutants is considerably affected by the genetic background. Ttc21baln/aln mutants on an FVB/NJ background develop a forebrain significantly smaller than mutants on a C57BL/6J background. We performed a Quantitative Trait Locus (QTL) analysis to identify potential genetic modifiers and identified two regions linked to differential forebrain size: modifier of alien QTL1 (Moaq1) on chromosome 4 at 27.8 Mb and Moaq2 on chromosome 6 at 93.6 Mb. These QTLs were validated by constructing congenic strains. Further analysis of Moaq1 identified a brain specific orphan G-protein coupled receptor (GPCR), Gpr63, as a candidate gene. We identified a SNP between the FVB and B6 strains in Gpr63, which creates a missense mutation predicted to be deleterious in the FVB protein. We first demonstrated that Gpr63 can localize to the cilium and then used CRISPR-Cas9 genome editing to create FVB congenic mice with the B6 sequence of Gpr63 and a deletion allele leading to a truncation of the GPR63 C-terminal tail. These alleles genetically interact with Ttc21baln/aln, validating Gpr63 as a forebrain modifier of Ttc21b and strongly supporting Gpr63 as the variant causal gene (i.e., the quantitative trait gene, QTG) for Moaq1.

scholarly journals Identification of Genetic Variants Regulating the Abundance of Clinically Relevant Plasma Proteins using the Diversity Outbred Mouse Model

2021 ◽  
Author(s):  
Stéphanie Philtjens ◽  
Dominic J. Acri ◽  
Byungwook Kim ◽  
Hyewon Kim ◽  
Jungsu Kim
Keyword(s):  
Genetic Variants ◽  
Quantitative Trait ◽  
Plasma Proteins ◽  
Systematic Investigation ◽  
Genetic Modifiers ◽  
Gene Encoding ◽  
Mouse Population ◽  
Aryl Hydrocarbon ◽  
Diversity Outbred ◽  
Trait Locus

Abstract Background: Levels of plasma proteins are under control of environmental and genetic factors. To use plasma proteins in biomarker studies, we need to understand how genetic modifiers influence their abundance. Although there has been expression quantitative trait loci (eQTL) studies on a few limited numbers of proteins, the effect of genetic variants on the levels of multiple plasma proteins still warrants more systematic investigation.Results: To identify genetic modifiers that influence the levels of clinically relevant plasma proteins, we performed protein quantitative trait locus (pQTL) mapping on the 92 proteins present in the Olink Mouse Exploratory Panel using the Diversity Outbred (DO) mouse population. We identified 12 significant pQTL that were located in cis and 6 that were in trans. Among them, we discovered that the presence of coding variants in the gene encoding for the Aryl Hydrocarbon Receptor (Ahr) had a significant effect on its abundance in plasma. Most interestingly, we identified variants in the Regulatory Factor X1 (Rfx1) gene that influence the abundance of the IL-17A protein in plasma.Conclusion: Our study reports an innovative pipeline for the identification of genetic modifiers that may be targeted for drug development.

scholarly journals Genomic Locus Modulating IOP in the BXD RI Mouse Strains

2017 ◽  
Author(s):  
Rebecca King ◽  
Ying Li ◽  
Jiaxing Wang ◽  
Felix L. Struebing ◽  
Eldon E. Geisert
Keyword(s):  
Candidate Genes ◽  
Quantitative Trait ◽  
Significant Quantitative Trait Locus ◽  
Interval Mapping ◽  
Mouse Strains ◽  
Genomic Locus ◽  
Quantitative Trait Analysis ◽  
Significant Locus ◽  
Trait Locus ◽  
Different Strains

AbstractPurposeIntraocular pressure (IOP) is the primary risk factor for developing glaucoma. The present study examines genomic contribution to the normal regulation of IOP in the mouse.MethodsThe BXD recombinant inbred (RI) strain set was used to identify genomic loci modulating IOP. We measured the IOP from 532 eyes from 33 different strains. The IOP data will be subjected to conventional quantitative trait analysis using simple and composite interval mapping along with epistatic interactions to define genomic loci modulating normal IOP.ResultsThe analysis defined one significant quantitative trait locus (QTL) on Chr.8 (100 to 106 Mb). The significant locus was further examined to define candidate genes that modulate normal IOP. There are only two good candidate genes within the 6 Mb over the peak, Cdh8 (Cadherin 8) and Cdh11 (Cadherin 11). Expression analysis on gene expression and immunohistochemistry indicate that Cdh11 is the best candidate for modulating the normal levels of IOP.ConclusionsWe have examined the genomic regulation of IOP in the BXD RI strain set and found one significant QTL on Chr. 8. Within this QTL that are two potential candidates for modulating IOP with the most likely gene being Cdh11.

Quantitative trait locus analysis of multiple agronomic traits in the model legume Lotus japonicus

Genome ◽  
2007 ◽  
Vol 50 (7) ◽  
pp. 627-637 ◽  
Author(s):  
Takahiro Gondo ◽  
Shusei Sato ◽  
Kenji Okumura ◽  
Satoshi Tabata ◽  
Ryo Akashi ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Agronomic Traits ◽  
Recombinant Inbred Lines ◽  
Lotus Japonicus ◽  
Seed Mass ◽  
Chromosome 2 ◽  
Seed Traits ◽  
Model Legume ◽  
Trait Locus

The first quantitative trait locus (QTL) analysis of multiple agronomic traits in the model legume Lotus japonicus was performed with a population of recombinant inbred lines derived from Miyakojima MG-20 × Gifu B-129. Thirteen agronomic traits were evaluated in 2004 and 2005: traits of vegetative parts (plant height, stem thickness, leaf length, leaf width, plant regrowth, plant shape, and stem color), flowering traits (flowering time and degree), and pod and seed traits (pod length, pod width, seeds per pod, and seed mass). A total of 40 QTLs were detected that explained 5%–69% of total variation. The QTL that explained the most variation was that for stem color, which was detected in the same region of chromosome 2 in both years. Some QTLs were colocated, especially those for pod and seed traits. Seed mass QTLs were located at 5 locations that mapped to the corresponding genomic positions of equivalent QTLs in soybean, pea, chickpea, and mung bean. This study provides fundamental information for breeding of agronomically important legume crops.

Genetic modifiers of otocephalic phenotypes inOtx2heterozygous mutant mice

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4347-4357 ◽  
Author(s):  
Takuichiro Hide ◽  
Jun Hatakeyama ◽  
Chiharu Kimura-Yoshida ◽  
E Tian ◽  
Naoki Takeda ◽  
...  
Keyword(s):  
Genetic Effect ◽  
Mutant Mice ◽  
Chromosome 2 ◽  
Genetic Modifiers ◽  
Lod Score ◽  
Craniofacial Malformations ◽  
Knock Out ◽  
Craniofacial Malformation ◽  
Replication Experiment ◽  
Significant Locus

Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most of the offspring of Otx2 knock-out chimeras, which are equivalent to the F1 of CBA and B6 strains, backcrossed with B6 females display reduction or loss of mandible, whereas those backcrossed with CBA females do not show noticeable phenotype at birth. The availability of phenotypically disparate strains renders identification of Otx2 modifier loci possible. In this study, a backcross of chimera with B6 was generated and genome-wide scans were conducted with polymorphic markers for non-mendelian distribution of alleles in Otx2 heterozygous mutant mice displaying abnormalities in the lower jaw. We identified one significant locus, Otmf18, between D18Mit68 and D18Mit120 on chromosomes 18, linked to the mandibular phenotype (LOD score 3.33). A similar replication experiment using a second backcross (N3) mouse demonstrated the presence of another significant locus, Otmf2 between D2Mit164 and D2Mit282 on chromosome 2, linked to the mandibular phenotype (LOD score 3.93). These two modifiers account for the distribution of the craniofacial malformations by the genetic effect between B6 and CBA strains. Moreover, Otmf2 contain a candidate gene for several diseases in mice and humans. These genetic studies involving an otocephalic mouse model appear to provide new insights into mechanistic pathways of craniofacial development. Furthermore, these experiments offer a powerful approach with respect to identification and characterization of candidate genes that may contribute to human agnathia-holoprosencephaly complex diseases.

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