“Henrietta and Harriet:” Considering the Marginalized Best Friend in Burney’s \u3cem\u3eCecilia\u3c/em\u3e and Austen’s \u3cem\u3eEmma\u3c/em\u3e

Although much has been said about the authorial relationship between Frances Burney and Jane Austen generally, there is a gap in scholarship discussing Austen’s Emma in context with the Burney’s Cecilia. This paper argues that there are notable threads—heiresses with absent or inadequate father figures, charity-case best friends, and rushed endings—connecting Emma and Cecilia. Tracing these threads allows us to examine the possible influence of Burney’s writing on Austen and also calls attention to the author’s different approaches to female agency and minor character space. To accomplish this task, I look at the narrative space given to minor characters in Burney’s Cecilia and Austen’s Emma. Specifically, I assess the roles of the minor characters Henrietta Belfield in Cecilia and Harriet Smith in Emma. Both of these minor female characters function as charity cases for the heroines they befriend, emphasizing Cecilia’s and Emma’s respective good fortunes and superior social standings. I argue that the links between these two minor characters serves as a launching point into further discussions about marginalized women in the long eighteenth century and Burney’s and Austen’s different attitudes on the role of women in society. In Cecilia, both the heroine and Henrietta suffer socially, financially, and emotionally as a result of the manipulations of men. Yet, in Emma, the relationship between the heroine and the socially inferior Harriet grants the female protagonist with the authority to be the manipulator rather than the manipulated. Through these asymmetrical relationships between the heroine and her lower-class friend, Burney situates the traditional role of women in society as fixed, where Austen criticizes and complicates these same roles

Copy number variant discrepancy resolution using the ClinGen dosage sensitivity map results in updated clinical interpretations in ClinVar

Conflict resolution in genomic variant interpretation is a critical step toward improving patient care. Evaluating interpretation discrepancies in copy number variants (CNVs) typically involves assessing overlapping genomic content with focus on genes/regions that may be subject to dosage sensitivity (haploinsufficiency (HI) and/or triplosensitivity (TS)). CNVs containing dosage sensitive genes/regions are generally interpreted as â likely pathogenicâ (LP) or â pathogenicâ (P), and CNVs involving the same known dosage sensitive gene(s) should receive the same clinical interpretation. We compared the Clinical Genome Resource (ClinGen) Dosage Map, a publicly available resource documenting known HI and TS genes/regions, against germline, clinical CNV interpretations within the ClinVar database. We identified 251 CNVs overlapping known dosage sensitive genes/regions but not classified as LP or P; these were sent back to their original submitting laboratories for reâ evaluation. Of 246 CNVs reâ evaluated, an updated clinical classification was warranted in 157 cases (63.8%); no change was made to the current classification in 79 cases (32.1%); and 10 cases (4.1%) resulted in other types of updates to ClinVar records. This effort will add curated interpretation data into the public domain and allow laboratories to focus attention on more complex discrepancies.The ClinGen Dosage Sensitivity (DS) Map provides evidenceâ based assessments of the haploinsufficiency and triplosensitivity of genes/genomic regions. We identified 251 clinical copy number variants (CNVs) in ClinVar that overlapped known DS genes/regions but were not interpreted as â likely pathogenicâ or â pathogenic;â these were sent back to their original laboratories for reâ evaluation. Of the 246 that were reâ evaluated, 63.0% resulted in updated classifications, showing that the ClinGen DS Map can be an effective initial step in CNV classification discrepancy resolution.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146425/1/humu23610_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146425/2/humu23610.pd

Characterization and Genomic Localization of a SMAD4 Processed Pseudogene

Like many clinical diagnostic laboratories, we undertake routine investigation of cancer-predisposed individuals by high-throughput sequencing of patient DNA that has been target-enriched for genes associated with hereditary cancer. Accurate diagnosis using such reagents requires alertness against rare nonpathogenic variants that may interfere with variant calling. In a cohort of 2042 such cases, we identified five that initially appeared to be carriers of a 95-bp deletion of SMAD4 intron 6. More detailed analysis indicated that these individuals all carried one copy of a SMAD4 processed gene. Because of its interference with diagnostic analysis, we characterized this processed gene in detail. Whole genome sequencing and confirmatory Sanger sequencing of junction PCR products were used to show that in each of the five cases, the SMAD4 processed gene was integrated at the same position on chromosome 9, located within the last intron of the SCAI gene. This rare polymorphic processed gene therefore reflects the occurrence of a single ancestral retrotransposition event. Compared to the reference SMAD4 mRNA sequence NM_005359.5 (https://www.ncbi.nlm.nih.gov/nucleotide/), the 5′ and 3′ UTR regions of the processed gene are both truncated, but its open reading frame is unaltered. Our experience leads us to advocate the use of an RNA-seq aligner, as part of diagnostic assay quality assurance, since this allows their recognition in a comparatively facile automated fashion

The (past, present) and future of internal medicine: is there an exit from the Slough of despond?

Detailed formal protocol with illustrations and extensive bibliography.UT Southwestern--Internal Medicin