Histone proteins are often noted for their high degree of sequence conservation. It is less often recognized that the histones are a heterogeneous protein family. Furthermore, several classes of non-histone proteins containing the histone fold motif exist. Novel histone and histone fold protein sequences continue to be added to public databases every year. The Histone Database (http://genome.nhgri.nih.gov/histones/) is a searchable, periodically updated collection of histone fold-containing sequences derived from sequence-similarity searches of public databases. Sequence sets are presented in redundant and non-redundant FASTA form, hotlinked to GenBank sequence files. Partial sequences are also now included in the database, which has considerably augmented its taxonomic coverage. Annotated alignments of full-length non-redundant sets of sequences are now available in both web-viewable (HTML) and downloadable (PDF) formats. The database also provides summaries of current information on solved histone fold structures, post-translational modifications of histones, and the human histone gene complement.
The Homeodomain Resource is a searchable, curated collection of information for the homeodomain protein family. The resource is organized in a compact form and provides user-friendly interfaces for both querying the component databases and assembling customized datasets. The current release (version 5.0, October 2002) contains 1056 full-length homeodomain-containing sequences, 37 experimentally-derived structures, 81 homeodomain interactions, 84 homeodomain DNA-binding sites and 114 homeodomain proteins implicated in human genetic disorders. A new feature of this new release is the inclusion of experimentally-derived protein-protein interaction data for homeodomain family members. All entries are cross-linked for easy retrieval of the original records from source databases. The Homeodomain Resource is freely available through the World Wide Web at http://research.nhgri.nih.gov/homeodomain/.
been reported to range from very low to levels equal to those in Caucasians. We report the results of completed BRCA1 and BRCA2 analyses in 20 African American families at risk for breast or ovarian cancer. Families were selected on the basis of a history of breast cancer or breast and ovarian cancer and further subdivided into the following categories: high-risk (three affected first-degree relatives; ten families), moderate-risk (two affected first-degree relatives; seven families) and undetermined-risk (single affected first-degree relative, with medical information being updated). BRCA1 and BRCA2 germline alterations were first detected using a series of exon-specific polymerase chain reaction primers for single-strand conformation polymorphism analysis; this was followed by DNA sequencing of polymorphism variants. A limited number of BRCA1 polymorphic intronic variants detected as a result of these studies were also analyzed for their effect on BRCA1 mRNA splicing using an assay developed by Myriad Genetics. In this cohort we detected one protein-truncating mutation in either BRCA1 or BRCA2 (1/20; 5%). However, we detected splice mutations, missense mutations and several polymorphic variants in both BRCA1 and BRCA2, with a much higher frequency in BRCA2. Many of these variants were both new and specific to African American patients; they also occurred in the absence of another disease-causing mutation. Moreover, a new BRCA1 missense mutation in one of the high-risk families, exon 19(W1718C), seems to co-segregate with breast cancer. We will report the relative frequencies of these BRCA1 and BRCA2 variants in patient and control populations. These results agree with previous observations that deleterious mutations in BRCA1 or BRCA2 are uncommon in at-risk African American patients. They indicate that more benign variants should be further evaluated for their potential role in the disease process in these patients and that additional, as yet unidentified, genetic factors may contribute to breast cancer risk in African American families. Baxevanis, Andreas D.[19]An integrated approach to the extraction, storage, processing and analysis of microarray gene expression data A single microarray experiment provides thousands of individual pieces of data; it is therefore essential to focus on effective informatics methods in order to draw new biological conclusions efficiently and confidently. We have developed a unified software package that meets several important needs in the area of microarray data analysis. The software achieves several goals: (1) Integrating algorithms developed at the National Human Genome Research Institute into NuTec's GLEAMS software system, creating a single, integrated core platform that is capable of handling the computational aspects of complementary DNA and oligonucleotide array analysis, including imaging, signal processing, data extraction, database management and higher-order data analysis. (2) Developing new bioinformatics strategies to deduce the sequence-and structure-based relat...
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