Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is ...difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array‐comparative genomic hybridization (array‐CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples 0.060%; 95% confidence interval (CI), 0.042–0.082. Array‐CGH showed that 22 markers were derived from non‐acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non‐acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non‐acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array‐CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.
Microarray‐based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates ...with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome‐wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty‐five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X‐linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre‐test information on IF.
Section Editor:
Aad Tibben, email: a.tibben@lumc.nl
The readout noise of a H2RG HgCdTe NIR detector from Teledyne is measured at a temperature T=105K. In a previous work, we have analysed the evolution of the readout noise as a function of the number ...of reads in terms of the frequency power spectrum of the noise with our in-house hybrid readout electronics. The new measurements with the SIDECARTM ASIC provided by Teledyne Imaging Sensors are compared to the previous ones. The noise power spectrum found can be used in a wide range of timing conditions and allows to predict quantitatively the 1/f effects arising from different time samplings. In contrast with most previous publications, we investigate the time properties of single pixel signals rather than the spatial correlations.
Non-syndromic arthrogryposis multiplex congenita (AMC) is characterized by multiple congenital contractures resulting from reduced fetal mobility. Genetic mapping and whole exome sequencing (WES) ...were performed in 31 multiplex and/or consanguineous undiagnosed AMC families. Although this approach identified known AMC genes, we here report pathogenic mutations in two new genes. Homozygous frameshift mutations in CNTNAP1 were found in four unrelated families. Patients showed a marked reduction in motor nerve conduction velocity (<10 m/s) and transmission electron microscopy (TEM) of sciatic nerve in the index cases revealed severe abnormalities of both nodes of Ranvier width and myelinated axons. CNTNAP1 encodes CASPR, an essential component of node of Ranvier domains which underlies saltatory conduction of action potentials along the myelinated axons, an important process for neuronal function. A homozygous missense mutation in adenylate cyclase 6 gene (ADCY6) was found in another family characterized by a lack of myelin in the peripheral nervous system (PNS) as determined by TEM. Morpholino knockdown of the zebrafish orthologs led to severe and specific defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6 encodes a protein that belongs to the adenylate cyclase family responsible for the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and upregulates myelinating signals. Our data indicate an essential and so far unknown role of ADCY6 in PNS myelination likely through the cAMP pathway. Mutations of genes encoding proteins of Ranvier domains or involved in myelination of Schwann cells are responsible for novel and severe human axoglial diseases.
The Nearby Supernova Factory (SNfactory) is an ambitious project to find and study in detail approximately 300 nearby Type Ia supernovae (SNe Ia) at redshifts 0.03<
z<0.08. This program will provide ...an exceptional data set of well-studied SNe in the nearby smooth Hubble flow that can be used as calibration for the current and future programs designed to use SNe to measure the cosmological parameters. The first key ingredient for this program is a reliable supply of Hubble-flow SNe systematically discovered in unprecedented numbers using the same techniques as those used in distant SNe searches. In 2002, 35 SNe were found using our test-bed pipeline for automated SN search and discovery. The pipeline uses images from the asteroid search conducted by the Near Earth Asteroid Tracking group at JPL. Improvements in our subtraction techniques and analysis have allowed us to increase our effective SN discovery rate to ∼12 SNe/month in 2003.
The antioxidant effect of lecithins was tested on several oils and fats varying in FA composition and tocopherol content. Standard lecithins, when added at a level of 1% w/w, exhibited a good ...protective effect against oxidation. This effect was observed to depend on the phospholipid content of the tested lecithins and the FA composition of the tested oils. Better results were obtained with lecithin samples containing high proportions of PC and PE. Indeed, the main antioxidant mechanism of lecithins was due to a synergistic effect between amino‐alcohol phospholipids and γ‐ and δ‐tocopherols. No synergism was observed with α‐tocopherols, especially when the tested oil was rich in linoleic acid. Therefore, the antioxidant protection of lecithins was not effective for sunflower oil. Finally, the use of fractionated or enriched lecithins was not clearly advantageous compared to standard oil lecithins.
The readout noise of a H2RG HgCdTe NIR detector from Teledyne is measured at a temperature T=110K. It is shown that a Fowler mode with n=240 allows to reach a noise of 2.63e (single read). A ...description of the power spectrum in terms of three parameters reproduces the variation of the noise as a function the number of Fowler samples as well as its dependence on the periodicity of the sampling. The variance of the noise decreases with frequency with an effective power of 0.62 in our measurement domain. The behaviour of the detector under different experimental conditions can then be predicted.
The readout noise of a H2RG HgCdTe NIR detector from Teledyne is measured at a temperature T=105 K. In a previous work, we have analysed the evolution of the readout noise as a function of the number ...of reads in terms of the frequency power spectrum of the noise with our in-house hybrid readout electronics. The new measurements with the SIDECARTM ASIC provided by Teledyne Imaging Sensors are compared to the previous ones. The noise power spectrum found can be used in a wide range of timing conditions and allows to predict quantitatively the 1/f effects arising from different time samplings. In contrast with most previous publications, we investigate the time properties of single pixel signals rather than the spatial correlations.
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