Visualization of Shared Genomic Regions and Meiotic Recombination in High-Density SNP Data

A fundamental goal of single nucleotide polymorphism (SNP) genotyping is to determine the sharing of alleles between individuals across genomic loci. Such analyses have diverse applications in defining the relatedness of individuals (including unexpected relationships in nominally unrelated individuals, or consanguinity within pedigrees), analyzing meiotic crossovers, and identifying a broad range of chromosomal anomalies such as hemizygous deletions and uniparental disomy, and analyzing population structure.We present SNPduo, a command-line and web accessible tool for analyzing and visualizing the relatedness of any two individuals using identity by state. Using identity by state does not require prior knowledge of allele frequencies or pedigree information, and is more computationally tractable and is less affected by population stratification than calculating identity by descent probabilities. The web implementation visualizes shared genomic regions, and generates UCSC viewable tracks. The command-line version requires pedigree information for compatibility with existing software and determining specified relationships even though pedigrees are not required for IBS calculation, generates no visual output, is written in portable C++, and is well-suited to analyzing large datasets. We demonstrate how the SNPduo web tool identifies meiotic crossover positions in siblings, and confirm our findings by visualizing meiotic recombination in synthetic three-generation pedigrees. We applied SNPduo to 210 nominally unrelated Phase I / II HapMap samples and, consistent with previous findings, identified six undeclared pairs of related individuals. We further analyzed identity by state in 2,883 individuals from multiplex families with autism and identified a series of anomalies including related parents, an individual with mosaic loss of chromosome 18, an individual with maternal heterodisomy of chromosome 16, and unexplained replicate samples.SNPduo provides the ability to explore and visualize SNP data to characterize the relatedness between individuals. It is compatible with, but distinct from, other established analysis software such as PLINK, and performs favorably in benchmarking studies for the analyses of genetic relatedness

Expression of coxsackie and adenovirus receptor distinguishes transitional cancer states in therapy-induced cellular senescence

Therapy-induced cellular senescence describes the phenomenon of cell cycle arrest that can be invoked in cancer cells in response to chemotherapy. Sustained proliferative arrest is often overcome as a contingent of senescent tumor cells can bypass this cell cycle restriction. The mechanism regulating cell cycle re-entry of senescent cancer cells remains poorly understood. This is the first report of the isolation and characterization of two distinct transitional states in chemotherapy-induced senescent cells that share indistinguishable morphological senescence phenotypes and are functionally classified by their ability to escape cell cycle arrest. It has been observed that cell surface expression of coxsackie and adenovirus receptor (CAR) is downregulated in cancer cells treated with chemotherapy. We show the novel use of surface CAR expression and adenoviral transduction to differentiate senescent states and also show in vivo evidence of CAR downregulation in colorectal cancer patients treated with neoadjuvant chemoradiation. This study suggests that CAR is a candidate biomarker for senescence response to antitumor therapy, and CAR expression can be used to distinguish transitional states in early senescence to study fundamental regulatory events in therapy-induced senescence

Retrospective and Prospective Study of Singapore Swing Method on Healing of Mastoid Cavity

Chronic suppurative otitis media with cholesteatoma is a common problem. The majority of ENT surgeons find the canal wall down operation to be the safest and simplest means of treating cholesteatoma. The ‘Singapore Swing’ is a method of promoting healing of mastoid cavity. In this study our main objective was to do Singapore Swing technique in larger number of cases, have long term follow-up and to compare its results with other mastoid operations in which obliteration has not been used. Patients of cholesteatoma were divided into case group and control group. The case group (26 patients) was operated by canal wall down procedure with Singapore Swing obliteration while the control group (62 patients) was operated by same method without any obliteration. Both retrospective and prospective studies were done. Time period of drying of mastoid cavity, numbers of visits to the hospital and hearing status were observed. Subjective satisfaction score of patient (0–10) and Surgeon’s satisfaction score (fully satisfied, partially satisfied and not satisfied at all) were measured in both the groups. The time of drying of cavity was <2 months in 88.5% of cases, while 27.5% of controls. Mean time of drying of cavity was 46 days (1½ months) in case group, while it was 89 days (3 months) in control group. Gain in air conduction was 11–30 dB in 33.3% cases and 15.7% of controls. 2 patients in control group had deterioration of 1–10 dB in air conduction. Subjective satisfaction score was 8–10 in 42.4% patients in case group, while 25% in control group. Surgeon was fully satisfied in 73% patients of case group and 45% patients of control group. The study suggested that Singapore Swing technique provides a dry, small and stable cavity with better hearing in less time