In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two Centaur objects: 2014 YY49 on 2019 January 28 and 2013 NL24 on ...2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius km and a geometric albedo for 2014 YY49 and a radius km and a geometric albedo for 2013 NL24. To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two Centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two Centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects' colors and light curve amplitudes and on follow-on occultation efforts informed by this astrometry.
Abstract
In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two Centaur objects: 2014 YY
49
on 2019 January 28 and 2013 ...NL
24
on 2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius
km and a geometric albedo
for 2014 YY
49
and a radius
km and a geometric albedo
for 2013 NL
24
. To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two Centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two Centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects’ colors and light curve amplitudes and on follow-on occultation efforts informed by this astrometry.
In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two centaur objects: 2014 YY\(_{49}\) on 2019 January 28 and 2013 ...NL\(_{24}\) on 2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius \(r=16^{+2}_{-1}\)km and a geometric albedo \(p_V=0.13^{+0.015}_{-0.024}\) for 2014 YY\(_{49}\), and a radius \(r=66 ^{+5}_{-5}\)km and geometric albedo \(p_V = 0.045^{+0.006}_{-0.008}\) for 2013 NL\(_{24}\). To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects' colors and light curve amplitudes, and on follow-on occultation efforts informed by this astrometry.
Conventional genetic testing of individuals with neurodevelopmental presentations and congenital anomalies (ND/CAs), i.e., the analysis of sequence and copy number variants, leaves a substantial ...proportion of them unexplained. Some of these cases have been shown to result from DNA methylation defects at a single locus (epi-variants), while others can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures). Here, we investigate the clinical diagnostic utility of genome-wide DNA methylation analysis of peripheral blood in unresolved ND/CAs. We generate a computational model enabling concurrent detection of 14 syndromes using DNA methylation data with full accuracy. We demonstrate the ability of this model in resolving 67 individuals with uncertain clinical diagnoses, some of whom had variants of unknown clinical significance (VUS) in the related genes. We show that the provisional diagnoses can be ruled out in many of the case subjects, some of whom are shown by our model to have other diseases initially not considered. By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case subjects with rare epi-variants, a portion of which involved genes clinically or functionally linked to the subjects’ phenotypes. This study demonstrates that genomic DNA methylation analysis can facilitate the molecular diagnosis of unresolved clinical cases and highlights the potential value of epigenomic testing in the routine clinical assessment of ND/CAs.
Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood ...DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.
Nontruncating sequence variants represent a major challenge in variant interpretation and classification. Here, we report a patient with features of Kabuki syndrome who carries two rare heterozygous ...variants in KMT2D: c.12935C>T, p.(Ser4312Phe) and c.15785‐10T>G. The clinical significance of these variants were discordantly interpreted by different diagnostic laboratories. Parental testing showed that the missense variant was inherited from the father with a mild Kabuki phenotype and the intronic variant from the mother with mosaic status. Through genome‐wide DNA methylation analysis of peripheral blood, we confirmed that the proband exhibited a previously described episignature of Kabuki syndrome. Parental samples had normal DNA methylation profiles, thus ruling out the involvement of the paternally inherited missense variant. RNA analysis revealed that the intronic change resulted in exon 49 skipping and frameshift, thereby providing a molecular diagnosis of Kabuki syndrome. This study demonstrates the utility of epigenomic and RNA analyses in resolving ambiguous clinical cases.
Background
Hereditary cancer predisposition syndromes account for approximately 10% of cancer cases. Next generation sequencing (NGS) based multi-gene targeted panels is now a frontline approach to ...identify pathogenic mutations in cancer predisposition genes in high-risk families. Recent evolvement of NGS technologies have allowed simultaneous detection of sequence and copy number variants (CNVs) using a single platform. In this study, we have analyzed frequency and nature of sequence variants and CNVs, in a Canadian cohort of patients, suspected with hereditary cancer syndrome, referred for genetic testing following specific genetic testing guidelines based on patient’s personal and/or family history of cancer.
Methods
A 2870 patients were subjected to a single NGS based multi-gene targeted hereditary cancer panel testing algorithm to identify sequence variants and CNVs in cancer predisposition genes at our reference laboratory in Southwestern Ontario. CNVs identified by NGS were confirmed by alternative techniques like Multiplex ligation-dependent probe amplification (MLPA).
Results
A 15% (431/2870) patients had a pathogenic variant and 36% (1032/2870) had a variant of unknown significance (VUS), in a cancer susceptibility gene. A total of 287 unique pathogenic variant were identified, out of which 23 (8%) were novel. CNVs identified by NGS based approach accounted for 9.5% (27/287) of pathogenic variants, confirmed by alternate techniques with high accuracy.
Conclusion
This study emphasizes the utility of NGS based targeted testing approach to identify both sequence and CNVs in patients suspected with hereditary cancer syndromes in clinical setting and expands the mutational spectrum of high and moderate penetrance cancer predisposition genes.
The Life Cycle Laurence D. Steinberg; Laurence D. Steinberg
1981.
eBook
THE PURPOSE OF THIS BOOK is to provide the student of human development with a collection of empirical and theoretical articles reflecting both contemporary and classic thinking in the field Although ...a good textbook can offer a thorough summary of information on development and, in some cases, a sensible organizational framework within which to place this information, there is really no substitute for reading important contributions in the original Above all, human development is a science, and it is important for the student to see how theories are developed and how our ideas about development are tested empirically.
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