Search results for "Base Sequence"
showing 10 items of 1146 documents
WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome
2018
International audience; Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like pheno…
Inferring heterozygosity from ancient and low coverage genomes
2016
Abstract While genetic diversity can be quantified accurately from high coverage sequencing data, it is often desirable to obtain such estimates from data with low coverage, either to save costs or because of low DNA quality, as is observed for ancient samples. Here, we introduce a method to accurately infer heterozygosity probabilistically from sequences with average coverage <1× of a single individual. The method relaxes the infinite sites assumption of previous methods, does not require a reference sequence, except for the initial alignment of the sequencing data, and takes into account both variable sequencing errors and potential postmortem damage. It is thus also applicable to …
Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type 10 (SCA10) expansions
2017
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta- and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 e…
Species complexes and phylogenetic lineages of Hoferellus (Myxozoa, Cnidaria) including revision of the genus: A problematic case for taxonomy
2015
Background Myxozoans are metazoan parasites whose traditional spore morphology-based taxonomy conflicts DNA based phylogenies. Freshwater species of the genus Hoferellus are parasites of the excretory system, with several members infecting food and ornamental fish species, as well as amphibians. This study aims to increase our understanding of their molecular diversity and development, aspects about which little is known, and to generate a molecular diagnostic tool to discriminate between different pathogenic and non-pathogenic Hoferellus spp. Methods SSU and ITS rDNA phylogeny, along with morphological descriptions using light and electron microscopy were used to identify and characterize …
Induction of the peroxisome proliferator activated receptor by fenofibrate in rat liver
1992
AbstractThe process of peroxisome proliferation in rodent liver by hypolipidemic compounds and related substances has recently been shown to be receptor-madiated. In the present study, we have examined the effect of oral administration of the strong peroxisome proliferator fenofibrate on the hepatic expression level of the peroxisome proliferator activated receptor (PPAR) in rats. Immunoblots of rat liver cytosols and nuclear extracs using antibodies raised against recombinant PPAR/β-galactosidase fusion proteins revealed a pronounced increase in the amount of PPAR protein in response to fenofibrate treatment. This induction could also be confirmed at the level or RNA by Northern blotting. …
Identification and characterization of a gene encoding a putative mouse Rho GTPase activating protein gene 8, Arhgap8.
2003
Rho GTPase activating proteins promote the intrinsic GTP hydrolysis activity of Rho family proteins. We isolated a putative mouse ortholog of the human Rho GTPase activating protein 8, ARHGAP8. The open reading frame encodes a peptide of 387 amino acids with high homology to human ARHGAP8 in its N-terminal domain. Both radiation hybrid mapping and fluorescent in situ hybridization localized the gene to mouse chromosome 15E. The 23 kb genomic Arhgap8 sequence consists of eight exons and seven introns. Northern blot and RT-PCR analyses showed that a transcript of approximately 1.9 kb is ubiquitously expressed in various adult mouse tissues with particularly strong expression in kidney.
Transcription intermediary factor 1γ is a tumor suppressor in mouse and human chronic myelomonocytic leukemia.
2011
Transcription intermediary factor 1γ (TIF1γ) was suggested to play a role in erythropoiesis. However, how TIF1γ regulates the development of different blood cell lineages and whether TIF1γ is involved in human hematological malignancies remain to be determined. Here we have shown that TIF1γ was a tumor suppressor in mouse and human chronic myelomonocytic leukemia (CMML). Loss of Tif1g in mouse HSCs favored the expansion of the granulo-monocytic progenitor compartment. Furthermore, Tif1g deletion induced the age-dependent appearance of a cell-autonomous myeloproliferative disorder in mice that recapitulated essential characteristics of human CMML. TIF1γ was almost undetectable in leukemic ce…
Post-transcriptional analysis of rat mitochondrial D-3-hydroxybutyrate dehydrogenase control through development and physiological stages.
1991
Abstract The nuclear encoded mitochondrial D -3-hydroxybutyrate dehydrogenase (BDH) is synthesized in the cytosal as a larger precursor. This membrane enzyme which requires lecithin for activity plays an essential role in energy metabolism as a ketone bodies-converting enzyme. A cDNA clone of the rat liver enzyme encompassing an antigenic determinant peptide has been isolated after immunoscreening of a λ gt11 expression library. The nucleotide sequence of this 279-base cDNA insert contains a single open reading frame of 93 amino-acids, which represents about a third of the mature enzyme. Amino-acid sequence analysis predicts a hydrophobic stretch of 29 amino-acids long which probably functi…
Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis.
2011
The gene for the atypical NOTCH ligand delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms that function in several developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally inherited chromosome. Here we show that mice that are deficient in Dlk1 have defects in postnatal neurogenesis in the subventricular zone: a developmental continuum that results in depletion of mature neurons in the olfactory bulb. We show that DLK1 is secreted by niche astrocytes, whereas its membrane-bound isoform is present in neural stem cells (NSCs) and is required for the inductive effect of secreted DLK1 on self-renewal. N…
Conserved role of Ras-GEFs in promoting aging: from yeast to mice
2011
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging, lifespan and metabolic parameters were analyzed in aged RasGrf1(-/-) mice. We observed that mice deficient for RasGrf1(-/-) display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals. Aged RasGrf1(-/-) displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1(-/-). IGF-I lev…