Role of DNA sequences outside the cores of DNase hypersensitive sites (HSs) in functions of the β-globin locus control region. Domain opening and synergism between HS2 and HS3

The roles of each DNase hypersensitive site (HS), and the DNA sequences between them, in the activity of the locus control region of the mammalian β-globin gene domain were examined by placing human and rabbit restriction fragments containing the cores of HS2, HS3, HS4, and HS5, along with varying amounts of flanking DNA, upstream of a hybrid ε-globin-luciferase reporter gene and testing for effects on expression both prior to and after integration into the chromosomes of K562 cells, a human erythroid cell line. Prior to integration, fragments containing HS2 enhanced expression to the greatest extent, and the modest enhancement by some fragments containing HS3 correlated with the presence of a well-conserved binding site for AP1/NFE2. The stronger effects of larger locus control region DNA fragments in clones of stably transfected cells indicates a role for sequences outside the HS cores after integration into the genome. The strong effect of a 1.9-kilobase HindIII fragment containing HS3 after, but not prior to, integration argues for the presence of a chromatin domain-opening activity. Use of a rabbit DNA fragment containing both HS2 and HS3 demonstrated a synergistic interaction between the two HSs when their natural context and spacing are preserved

Fast and Space-Efficient Location of Heavy or Dense Segments in Run-Length Encoded Sequences

This paper considers several variations of an optimization problem with potential applications in such areas as biomolecular sequence analysis and image processing. Given a sequence of items, each with a weight and a length, the goal is to find a subsequence of consecutive items of optimal value, where value is either total weight or total weight divided by total length. There may also be a specified lower and/or upper bound on the acceptable length of subsequences. This paper shows that all the variations of the problem are solvable in linear time and space even with non-uniform item lengths and divisible items, implying that run-length encoded sequences can be handled in time and space linear in the number of runs. Furthermore, some problem variations can be solved in constant space. Also, these time and space bounds suffice for certain problem variations in which we call for reporting of many “good” subsequences

Clinically relevant updates of the HbVar database of human hemoglobin variants and thalassemia mutations

HbVar (http://globin.bx.psu.edu/hbvar) is a widely-used locus-specific database (LSDB) launched 20 years ago by a multi-center academic effort to provide timely information on the numerous genomic variants leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Here, we report several advances for the database. We made clinically relevant updates of HbVar, implemented as additional querying options in the HbVar query page, allowing the user to explore the clinical phenotype of compound heterozygous patients. We also made significant improvements to the HbVar front page, making comparative data querying, analysis and output more user-friendly. We continued to expand and enrich the regular data content, involving 1820 variants, 230 of which are new entries. We also increased the querying potential and expanded the usefulness of HbVar database in the clinical setting. These several additions, expansions and updates should improve the utility of HbVar both for the globin research community and in a clinical setting

Sharing data between LSDBs and central repositories.

Several Locus-Specific DataBases (LSDBs) have recently been approached by larger, more general data repositories (including NCBI and UCSC) with the request to share the DNA variant data they have collected. Within the Human Genome Variation Society (HGVS) a document was generated summarizing the issues related to these requests. The document has been circulated in the HGVS/LSDB community and was discussed extensively. Here we summarize these discussions and present the concluded recommendations for LSDB data sharing with central repositories