Deletion of a conserved noncoding sequence in <i>Plzf</i> intron leads to <i>Plzf</i> down‐regulation in limb bud and polydactyly in the rat

Liška, František; Šnajdr, Pavel; Šedová, Lucie; Šeda, Ondřej; Chylíková, Blanka; Slámová, Petra; Krejčí, Eliška; Sedmera, David; Grim, Miloš; Křenová, D; Křen, Vladimı́r

doi:10.1002/dvdy.21859

Cited by 22 publications

(17 citation statements)

References 52 publications

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“…Relative weights of retroperitoneal fat differed among the strains in F2 generation of programmed males, with SHR having higher relative weights. Strains used in this study differed in a single gene mutation-254 kb deletion in intronic region of Zbtb16 gene of the PD/Cub strain origin [37]. The genomic background of SHR was thought to exacerbate the effects of Zbtb16 gene involved in pathogenesis of metabolic syndrome [18], but conversely was shown to improve the related parameters [20], which was to an extent apparent in our study as well.…”

Section: Discussionsupporting

confidence: 56%

Grandmother’s Diet Matters: Early Life Programming with Sucrose Influences Metabolic and Lipid Parameters in Second Generation of Rats

2020

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Early life exposure to certain environmental stimuli is related to the development of alternative phenotypes in mammals. A number of these phenotypes are related to an increased risk of disease later in life, creating a massive healthcare burden. With recent focus on the determination of underlying causes of common metabolic disorders, parental nutrition is of great interest, mainly due to a global shift towards a Western-type diet. Recent studies focusing on the increase of food or macronutrient intake don’t always consider the source of these nutrients as an important factor. In our study, we concentrate on the effects of high-sucrose diet, which provides carbohydrates in form of sucrose as opposed to starch in standard diet, fed in pregnancy and lactation in two subsequent generations of spontaneously hypertensive rats (SHR) and congenic SHR-Zbtb16 rats. Maternal sucrose intake increased fasting glycaemia in SHR female offspring in adulthood and increased their chow consumption in gravidity. High-sucrose diet fed to the maternal grandmother increased brown fat weight and HDL cholesterol levels in adult male offspring of both strains, i.e., the grandsons. Fasting glycaemia was however decreased only in SHR offspring. In conclusion, we show the second-generation effects of maternal exposition to a high-sucrose diet, some modulated to a certain extent by variation in the Zbtb16 gene.

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Section: Discussionsupporting

confidence: 56%

Grandmother’s Diet Matters: Early Life Programming with Sucrose Influences Metabolic and Lipid Parameters in Second Generation of Rats

2020

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“…Using a dynamic window binning approach to identify genomic segments with differential NGS read coverage (DWAC-Seq; VG, manuscript in preparation), we identified four duplications in BN- Lx and four deletions compared to the BN reference, including a known 3 kb deletion on chromosome 8 [14]. In SHR we identified 384 duplications and 461 deletions (Figure 1b).…”

Section: Resultsmentioning

confidence: 99%

Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel

et al. 2012

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BackgroundWith the advent of next generation sequencing it has become possible to detect genomic variation on a large scale. However, predicting which genomic variants are damaging to gene function remains a challenge, as knowledge of the effects of genomic variation on gene expression is still limited. Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression.ResultsWe generated a comprehensive inventory of genomic differences between the two founder strains of the rat HXB/BXH recombinant inbred panel: SHR/OlaIpcv and BN-Lx/Cub. We identified 3.2 million single nucleotide variants, 425,924 small insertions and deletions, 907 copy number changes and 1,094 large structural genetic variants. RNA-sequencing analyses on liver tissue of the two strains identified 532 differentially expressed genes and 40 alterations in transcript structure. We identified both coding and non-coding variants that correlate with differential expression and alternative splicing. Furthermore, structural variants, in particular gene duplications, show a strong correlation with transcriptome alterations.ConclusionsWe show that the panel is a good model for assessing the genetic basis of phenotypic heterogeneity and for providing insights into possible underlying molecular mechanisms. Our results reveal a high diversity and complexity underlying quantitative and qualitative transcriptional differences.

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“…However, the evidence is also clear that sequence conservation does not detect all regulatory elements, nor does it provide any assurance that the predicted sites are functional. Thus, sequence conservation is most effective when used in conjunction with other corroborating techniques, particularly ones that can assess chromatin changes linked to transcriptional activity [149,152,162,[168][169][170][171]. In studies to identify regulatory sequences that direct FSHR/Fshr transcription, results from transgenic and promoter studies shifted the experimental focus away from the promoter to the region encompassing all of FSHR/Fshr and its adjoining intergenic regions, which required a new set of tools and resources that fortunately evolved from the collection of genome sequences and efforts to understand their content.…”

Section: The Search For New Regulatory Elementsmentioning

confidence: 99%

Current Concepts of Follicle-Stimulating Hormone Receptor Gene Regulation1

George

Dille

Heckert

2011

Biology of Reproduction

109

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Follicle-stimulating hormone (FSH), a pituitary glycoprotein hormone, is an integral component of the endocrine axis that regulates gonadal function and fertility. To transmit its signal, FSH must bind to its receptor (FSHR) located on Sertoli cells of the testis and granulosa cells of the ovary. Thus, both the magnitude and the target of hormone response are controlled by mechanisms that determine FSHR levels and cell-specific expression, which are supported by transcription of its gene. The present review examines the status of FSHR/Fshr gene regulation, emphasizing the importance of distal sequences in FSHR/Fshr transcription, new insights gained from the influx of genomics data and bioinformatics, and emerging trends that offer direction in deciphering the FSHR/Fshr regulatory landscape.

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Deletion of a conserved noncoding sequence in Plzf intron leads to Plzf down‐regulation in limb bud and polydactyly in the rat

Cited by 22 publications

References 52 publications

Grandmother’s Diet Matters: Early Life Programming with Sucrose Influences Metabolic and Lipid Parameters in Second Generation of Rats

Grandmother’s Diet Matters: Early Life Programming with Sucrose Influences Metabolic and Lipid Parameters in Second Generation of Rats

Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel

Current Concepts of Follicle-Stimulating Hormone Receptor Gene Regulation1

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