Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms (SNPs) have been the major focus of most large-scale comparative genomics studies to date. Here, we discuss a third, largely ignored, type of genetic variation, namely changes in tandem repeat number. Historically, tandem repeats have been designated as non functional “junk” DNA, mostly as a result of their highly unstable nature. With the exception of tandem repeats involved in human neurodegenerative diseases, repeat variation was often believed to be neutral with no phenotypic consequences. Recent studies, however, have shown that as many as 10% to 20% of coding and regulatory sequences in eukaryotes contain an unstable repeat tract. Contrary to initial suggestions, tandem repeat variation can have useful phenotypic consequences. Examples include rapid variation in microbial cell surface, tuning of internal molecular clocks in flies and the dynamic morphological plasticity in mammals. As such, tandem repeats can be useful functional elements that facilitate evolvability and rapid adaptation.

Ultrasonography and CT cannot reliably exclude occult groin abnormalities. Patients with clinical suspicion of inguinal hernia should undergo MRI as the definitive radiologic examination.

Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use.

Genomic imprinting is an epigenetic inheritance system characterized by parental allele-specific gene expression. Allele-specific DNA methylation and chromatin composition are two epigenetic modification systems that control imprinted gene expression. To get a general assessment of histone lysine acetylation at imprinted genes we measured allele-specific acetylation of a wide range of lysine residues, H3K4, H3K18, H3K27, H3K36, H3K79, H3K64, H4K5, H4K8, H4K12, H2AK5, H2BK12, H2BK16 and H2BK46 at 11 differentially methylated regions (DMRs) in reciprocal mouse crosses using multiplex chromatin immunoprecipitation SNuPE assays. Histone acetylation marks generally distinguished the methylation-free alleles from methylated alleles at DMRs in mouse embryo fibroblasts and embryos. Acetylated lysines that are typically found at transcription start sites exhibited stronger allelic bias than acetylated histone residues in general. Maternally methylated DMRs, that usually overlap with promoters exhibited higher levels of acetylation and a 10% stronger allele-specific bias than paternally methylated DMRs that reside in intergenic regions. Along the H19/Igf2 imprinted domain, allele-specific acetylation at each lysine residue depended on functional CTCF binding sites in the imprinting control region. Our results suggest that many different histone acetyltransferase and histone deacetylase enzymes must act in concert in setting up and maintaining reciprocal parental allelic histone acetylation at DMRs.

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Background Current approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined. Methods We recruited 468 subjects with C. difficile infection at Mayo Clinic Rochester between May and December 2016 and performed whole genome sequencing (WGS) on C. difficile isolates from 397. WGS was also performed on isolates from a subset of the subjects at the time of recurrence of infection. Sequence data were analyzed by determining core genome multilocus sequence type (cgMLST), with isolates grouped by allelic differences and predicted ribotype. Results There was no correlation between C. difficile isolates based on cgMLST or ribotype groupings and CDI outcome. Epidemiologic assessment of hospitalized subjects harboring C. difficile isolates with ≤2 allelic differences based on standard infection prevention and control assessment revealed no evidence of person-to-person transmission. Interestingly, community-acquired CDI subjects in 40% of groups with ≤2 allelic differences resided within the same zip code. Among 18 subjects clinically classified as having recurrent CDI, WGS revealed 14 with initial and subsequent isolates differing by ≤2 allelic differences, suggesting relapse of infection with the same initial strain, and 4 with isolates differing by >50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having reinfection based on timing of recurrence, 3 had isolates with ≤2 allelic differences between them suggesting relapse, with 2 having isolates differing by >50 allelic differences - suggesting reinfection. Conclusions Our findings point to potential transmission of C. difficile in the community. WGS better differentiates relapse from reinfection than do definitions based on timing of recurrence.

Large-scale sequencing studies of head and neck squamous cell carcinoma (HNSCC) have elucidated the genetic changes that characterize HNSCC. These findings have supported the development of therapeutic strategies that target key components of aberrant signaling pathways and immune dysregulation. Cumulative evidence suggests that these agents in combination with radiotherapy may have synergistic effects. This review highlights the predictive biomarkers that have been identified from HNSCC genomic studies and implications on the development of molecular-targeting agents that may effectively treat patients with HNSCC, especially when used in combination with radiation.

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