Adiposity QTL Adip20 decomposes into at least four loci when dissected using congenic strains

AbstractAn average mouse in midlife weighs between 25 and 30 g, with about a gram of tissue in the largest adipose depot (gonadal), and the weight of this depot differs between inbred strains. Specifically, C57BL/6ByJ mice have heavier gonadal depots on average than do 129P3/J mice. To understand the genetic contributions to this trait, we mapped several quantitative trait loci (QTLs) for gonadal depot weight in an F2 intercross population. Our goal here was to fine-map one of these QTLs, Adip20 (formerly Adip5), on mouse chromosome 9. To that end, we analyzed the weight of the gonadal adipose depot from newly created congenic strains. Results from the sequential comparison method indicated at least four rather than one QTL; two of the QTLs were less than 0.5 Mb apart, with opposing directions of allelic effect. Different types of evidence (missense and regulatory genetic variation, human adiposity/body mass index orthologues, and differential gene expression) implicated numerous candidate genes from the four QTL regions. These results highlight the value of mouse congenic strains and the value of this sequential method to dissect challenging genetic architecture.

Download Full-text

Discovery and refinement of muscle weight QTLs in B6 × D2 advanced intercross mice

Physiological Genomics ◽

10.1152/physiolgenomics.00055.2014 ◽

2014 ◽

Vol 46 (16) ◽

pp. 571-582 ◽

Cited By ~ 9

Author(s):

P. Carbonetto ◽

R. Cheng ◽

J. P. Gyekis ◽

C. C. Parker ◽

D. A. Blizard ◽

...

Keyword(s):

Inbred Strains ◽

Mouse Strains ◽

Missense Mutations ◽

Muscle Weight ◽

Hindlimb Muscles ◽

Hindlimb Muscle ◽

Causal Genes ◽

Snp Panel ◽

Genomic Regions ◽

Genetic Contributions

The genes underlying variation in skeletal muscle mass are poorly understood. Although many quantitative trait loci (QTLs) have been mapped in crosses of mouse strains, the limited resolution inherent in these conventional studies has made it difficult to reliably pinpoint the causal genetic variants. The accumulated recombination events in an advanced intercross line (AIL), in which mice from two inbred strains are mated at random for several generations, can improve mapping resolution. We demonstrate these advancements in mapping QTLs for hindlimb muscle weights in an AIL ( n = 832) of the C57BL/6J (B6) and DBA/2J (D2) strains, generations F8–F13. We mapped muscle weight QTLs using the high-density MegaMUGA SNP panel. The QTLs highlight the shared genetic architecture of four hindlimb muscles and suggest that the genetic contributions to muscle variation are substantially different in males and females, at least in the B6D2 lineage. Out of the 15 muscle weight QTLs identified in the AIL, nine overlapped the genomic regions discovered in an earlier B6D2 F2 intercross. Mapping resolution, however, was substantially improved in our study to a median QTL interval of 12.5 Mb. Subsequent sequence analysis of the QTL regions revealed 20 genes with nonsense or potentially damaging missense mutations. Further refinement of the muscle weight QTLs using additional functional information, such as gene expression differences between alleles, will be important for discerning the causal genes.

Download Full-text

Differential gene expression in different types of Hevea brasiliensis roots

Plant Science ◽

10.1016/j.plantsci.2011.08.005 ◽

2012 ◽

Vol 183 ◽

pp. 149-158 ◽

Cited By ~ 8

Author(s):

Riza-Arief Putranto ◽

Christine Sanier ◽

Julie Leclercq ◽

Cuifang Duan ◽

Maryannick Rio ◽

...

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Hevea Brasiliensis ◽

Different Types ◽

Differential Gene

Download Full-text

A locus on mouse Chromosome 9 (Adip5) affects the relative weight of the gonadal but not retroperitoneal adipose depot

Mammalian Genome ◽

10.1007/s00335-006-0055-1 ◽

2006 ◽

Vol 17 (11) ◽

pp. 1078-1092 ◽

Cited By ~ 17

Author(s):

Amanda H. McDaniel ◽

Xia Li ◽

Michael G. Tordoff ◽

Alexander A. Bachmanov ◽

Danielle R. Reed

Keyword(s):

Mouse Chromosome ◽

Relative Weight ◽

Chromosome 9 ◽

Adipose Depot

Download Full-text

Differential gene expression in skeletal organic matrix proteins of scleractinian corals associated with mixed aragonite/calcite skeletons under low mMg/Ca conditions

PeerJ ◽

10.7717/peerj.7241 ◽

2019 ◽

Vol 7 ◽

pp. e7241 ◽

Cited By ~ 6

Author(s):

Ikuko Yuyama ◽

Tomihiko Higuchi

Keyword(s):

Matrix Protein ◽

Organic Matrix ◽

Matrix Proteins ◽

Rna Seq ◽

Coral Skeletons ◽

Different Types ◽

Key Factor ◽

Acropora Tenuis ◽

Differential Gene ◽

Selective Formation

Although coral skeletons generally comprise aragonite crystals, changes in the molar Mg/Ca ratio (mMg/Ca) in seawater result in the incorporation of calcite crystals. The formation mechanism of aragonite and calcite crystals in the scleractinian coral Acropora tenuis was therefore investigated by RNA-seq analysis, using early growth stage calcite (mMg/Ca = 0.5) and aragonite (mMg/Ca = 5.2)-based corals. As a result, 1,287 genes were up-regulated and 748 down-regulated in calcite-based corals. In particular, sixty-eight skeletogenesis-related genes, such as ectin, galaxin, and skeletal aspartic acid-rich protein, were detected as up-regulated, and six genes, such as uncharacterized skeletal organic matrix protein 5, down-regulated, in low-Mg/Ca conditions. Since the number of down-regulated genes associated with the skeletal organic matrix of aragonite skeletons was much lower than that of up-regulated genes, it is thought that corals actively initiate construction of an aragonite skeleton by the skeletal organic matrix in low-Mg/Ca conditions. In addition, different types of skeletal organic matrix proteins, extracellular matrix proteins and calcium ion binding proteins appeared to change their expression in both calcite-formed and normal corals, suggesting that the composition of these proteins could be a key factor in the selective formation of aragonite or calcite CaCO3.

Download Full-text

ADHD genetics

10.1093/med/9780198739258.003.0003 ◽

2018 ◽

Author(s):

Kate Langley

Keyword(s):

Genetic Factors ◽

Rare Variants ◽

Association Studies ◽

Copy Number Variant ◽

Polygenic Risk Score ◽

Genome Wide Association Studies ◽

Clinical Factors ◽

Genome Wide ◽

Different Types ◽

Genetic Contributions

This chapter reviews the evidence suggesting that there is a strong genetic component to ADHD and the efforts to identify the specific genetic factors that might be involved. It discusses the different types of genetic contributions, from common to rare variants, and the evidence that these are involved in the aetiology of the disorder. An overview of the methodological strategies employed, including genome-wide association studies (GWAS), polygenic risk score, and copy number variant (CNV) analyses, is undertaken, as well as discussion of the strengths and pitfalls of such work. The contradictory findings in the field and controversies that arise as a result are also explored. Finally, this chapter considers how the heritability of ADHD and specific genetic factors involved need to be examined in the context of clinical factors such as comorbidity and how these factors affect investigations into the genetics of ADHD.

Download Full-text

DISTRIBUTION OF A CROSS-REACTIVE IDIOTYPIC SPECIFICITY IN INBRED STRAINS OF MICE

Journal of Experimental Medicine ◽

10.1084/jem.137.4.855 ◽

1973 ◽

Vol 137 (4) ◽

pp. 855-869 ◽

Cited By ~ 40

Author(s):

Laura L. Pawlak ◽

Alfred Nisonoff

Keyword(s):

Heavy Chain ◽

Parental Strain ◽

Inbred Strains ◽

The Other ◽

Congenic Mice ◽

Congenic Strains ◽

Inbred Strains Of Mice ◽

F1 Progeny ◽

The Cross

The expression of an idiotype characteristic of anti-p-azophenylarsonate antibodies of all A/J mice was explored in F1 progeny, in other inbred strains, and in congenic mice. Of the strains tested only those closely related to A/J produced antibodies with the cross-reactive idiotype (CRI). None of the mice synthesized intermediate levels of CRI. No relationship between H-2 type and idiotype was noted. Congenic mice with a strain A background but a different H-2 type produced CRI in amounts quantitatively equivalent to those of strain A mice. Conversely, the presence of the H-2 genotype of strain A on an unrelated background was not associated with the formation of CRI. Nearly all F1 progeny of strain A mice formed CRI, indicating that failure of the other (non-A) parental strain to produce CRI is not attributable to the presence of a gene controlling the synthesis of a suppressor of CRI. NZB mice, which have the same heavy chain allotype as strain A, but are unrelated in origin, failed to produce CRI, although allotype has been shown to be linked to idiotype in congenic strains.

Download Full-text

H-2 mutation affecting immune response to Thy-1.1 antigen

Journal of Experimental Medicine ◽

10.1084/jem.145.6.1602 ◽

1977 ◽

Vol 145 (6) ◽

pp. 1602-1606 ◽

Cited By ~ 13

Author(s):

M Zaleski ◽

J Klein

Keyword(s):

Immune Response ◽

Inbred Mice ◽

Serum Antibody ◽

Inbred Strains ◽

Antibody Responses ◽

Chromosome 9 ◽

Chromosome 17 ◽

Target Cells ◽

Histocompatibility Complex ◽

The Right

Mouse thymus, thymus-derived lymphocytes, and brain share an antigen determined by gene at the Thy-1 locus in chromosome 9 (1). Two alleles have been identified at this locus: Thy-1(a), coding for antigen Thy-1.1 (or θ-AKR) present in AKR and seven other strains; and Thy-1(b), coding for antigen Thy-1.2 (or{teta}-C3H) and present in C3H and all the remaining inbred strains. Injection of AKR thymocytes into inbred mice carrying the Thy-1(b) allele results in an immune response that can be measured either serologically by determining the level of antibodies in the recipients serum (1) or by counting plaque- forming cells (PFC) detectable in spleens of the recipients by means of an assay, with AKR thymocytes as target cells(2). The magnitude of PFC and serum antibody responses after a single thymocyte injection depends on the genetic make-up of the recipient. Three genes controlling the PFC response to the Thy- 1.1 antigen have been identified: Ir-Thy-1A and Ir-Thy-1B, which are closely linked to the major histocompatibility complex (H-2) of the mouse (3-6), and Ir-5, which is located at a distance of 17 cm to the right of the H-2 complex on chromosome 17 (6). Previous genetic mapping with H-2 recombinant strains has indicated that the two Ir-Thy-1 loci are located to the left of the IC subregion (7). Further experiments strongly suggested that either one or both Ir-Thy-1 loci map to the K rather than the I region of the H-2 complex (8). In this report, the study of an H- 2 mutant, CBA-H-2(ka) (M523) (9), and its parental strain, CBA/LacStoY (CBA) provided further evidence that one of these loci apparently resides in the K region and might even be identical with the H-2K locus in that region.

Download Full-text

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression

BioMed Research International ◽

10.1155/2020/2489175 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Biao Xie ◽

Wei Zhang ◽

Qi Zhang ◽

Qiuju Zhang ◽

Yupeng Wang ◽

...

Keyword(s):

Renal Injury ◽

Underlying Mechanism ◽

Henoch Schonlein Purpura ◽

Tandem Mass Tag ◽

Different Types ◽

Differential Gene ◽

Proteomic Analyses ◽

Schonlein Purpura ◽

Henoch Schönlein Purpura ◽

Purpura Nephritis

Background. Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression. Methods. RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3×type 1, 3×type 2, and 3×type 3). Student’s t-tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results. A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. Conclusions. Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.

Download Full-text