Human genome report card.

Description based on: March 1993; title from cover.

1997 Delegates to the Second International Strategy Meeting on Human Genome Sequencing in Bermuda from Gert-Jan van Ommen

Photographs from the February 1997 Bermuda meeting. Courtesy of Gert-Jan van Ommen.

Beyond the human genome: microbes, metaphors and what it means to be human in an interconnected post-genomic world

Four years after the completion of the Human Genome Project, the US National Institutes for Health launched the Human Microbiome Project on 19 December 2007. Using metaphor analysis, this article investigates reporting in English-language newspapers on advances in microbiomics from 2003 onwards, when the word “microbiome” was first used. This research was said to open up a “new frontier” and was conceived as a “second human genome project”, this time focusing on the genomes of microbes that inhabit and populate humans rather than focusing on the human genome itself. The language used by scientists and by the journalists who reported on their research employed a type of metaphorical framing that was very different from the hyperbole surrounding the decipherment of the “book of life”. Whereas during the HGP genomic successes had been mainly framed as being based on a unidirectional process of reading off information from a passive genetic or genomic entity, the language employed to discuss advances in microbiomics frames genes, genomes and life in much more active and dynamic ways.

Manipulação do genoma humano: ética e direito

A biologia molecular tem fornecido as ferramentas básicas para os geneticistas se aprofundarem nos mecanismos moleculares que influem na variação das doenças. Deve-se destacar a responsabilidade científica e moral dos pesquisadores, uma vez que os cientistas devem imaginar as consequências morais da aplicação comercial de testes genéticos, já que esse fato envolve não só o indivíduo e suas famílias, mas toda a população. Além de ser preciso, também, fazer uma reflexão sobre como essas informações do genoma humano serão utilizadas, para o bem ou mal. O objetivo desta revisão foi trazer à luz do conhecimento dados sobre características éticas da aplicação da biologia molecular, relacionando-a com os direitos do ser humano. Após análise bibliográfica, pôde-se observar que o Projeto Genoma Humano gerou várias possibilidades, como identificação de genes associados a doenças com propriedades sinergísticas, mas modificando às vezes comportamentos ao intervir geneticamente no ser humano, trazendo benefícios ou malefícios sociais. O grande desafio é decidir o que a humanidade pretende em relação a este gigantesco salto.

Molecular markers and genetic diversity of Plasmodium vivax

Enhanced understanding of the transmission dynamics and population genetics for Plasmodium vivax is crucial in predicting the emergence and spread of novel parasite phenotypes with major public health implications, such as new relapsing patterns, drug resistance and increased virulence. Suitable molecular markers are required for these population genetic studies. Here, we focus on two groups of molecular markers that are commonly used to analyse natural populations of P. vivax. We use markers under selective pressure, for instance, antigen-coding polymorphic genes, and markers that are not under strong natural selection, such as most minisatellite and microsatellite loci. First, we review data obtained using genes encoding for P. vivax antigens: circumsporozoite protein, merozoite surface proteins 1 and 3α, apical membrane antigen 1 and Duffy binding antigen. We next address neutral or nearly neutral molecular markers, especially microsatellite loci, providing a complete list of markers that have already been used in P. vivax populations studies. We also analyse the microsatellite loci identified in the P. vivax genome project. Finally, we discuss some practical uses for P. vivax genotyping, for example, detecting multiple-clone infections and tracking the geographic origin of isolates.

No-match ORESTES explored as tumor markers

Sequencing technologies and new bioinformatics tools have led to the complete sequencing of various genomes. However, information regarding the human transcriptome and its annotation is yet to be completed. The Human Cancer Genome Project, using ORESTES (open reading frame EST sequences) methodology, contributed to this objective by generating data from about 1.2 million expressed sequence tags. Approximately 30 of these sequences did not align to ESTs in the public databases and were considered no-match ORESTES. On the basis that a set of these ESTs could represent new transcripts, we constructed a cDNA microarray. This platform was used to hybridize against 12 different normal or tumor tissues. We identified 3421 transcribed regions not associated with annotated transcripts, representing 83.3 of the platform. The total number of differentially expressed sequences was 1007. Also, 28 of analyzed sequences could represent noncoding RNAs. Our data reinforces the knowledge of the human genome being pervasively transcribed, and point out molecular marker candidates for different cancers. To reinforce our data, we confirmed, by real-time PCR, the differential expression of three out of eight potentially tumor markers in prostate tissues. Lists of 1007 differentially expressed sequences, and the 291 potentially noncoding tumor markers were provided.

Wolbachia genomes and the many faces of symbiosis

How could scientists working on the pathogenesis of filarial diseases, speciation and parthenogenesis in insects, sex-ratio deviations in crustaceans, pest control, and the evolution of bacterial genomes be united? How could a common research project attract the interest of these scientists? How could parasitology be made even more multi-disciplinary? Two workshops organized by New England Biolabs Inc. (Beverly, MA, USA) provide a simple answer to these questions: studying the genomes of Wolbachia endosymbionts.

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma

Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.

MR MAQ: algorisme de Read Mapping utilitzant la plataforma Hadoop

L’èxit del Projecte Genoma Humà (PGH) l’any 2000 va fer de la “medicina personalitzada” una realitat més propera. Els descobriments del PGH han simplificat les tècniques de seqüenciació de tal manera que actualment qualsevol persona pot aconseguir la seva seqüència d’ADN complerta. La tecnologia de Read Mapping destaca en aquest tipus de tècniques i es caracteritza per manegar una gran quantitat de dades. Hadoop, el framework d’Apache per aplicacions intensives de dades sota el paradigma Map Reduce, resulta un aliat perfecte per aquest tipus de tecnologia i ha sigut l’opció escollida per a realitzar aquest projecte. Durant tot el treball es realitza l’estudi, l’anàlisi i les experimentacions necessàries per aconseguir un Algorisme Genètic innovador que utilitzi tot el potencial de Hadoop.

Update of the Gene Discovery Program in Schistosoma mansoni with the Expressed Sequence Tag Approach

Continuing the Schistosoma mansoni Genome Project 363 new templates were sequenced generating 205 more ESTs corresponding to 91 genes. Seventy four of these genes (81%) had not previously been described in S. mansoni. Among the newly discovered genes there are several of significant biological interest such as synaptophysin, NIFs-like and rho-GDP dissociation inhibitor

Dermatologie. 2009: quoi de neuf en dermatologie [Dermatology]

Many significant advances in dermatology were published during 2009, focussing on infectious diseases, inflammatory disorders and oncology. Molecular medicine, as a result of the human genome project, also modifies the field of dermatology. Bioinformatics and biotechnology revolutionize the daily clinical practice in dermatology. A change of paradigm occurs notably in infectious diseases.

Leishmania cysteine proteinases: from gene to subunit vaccine.

Whole genome sequences of microbial pathogens present new opportunities for clinical application. Presently, genome sequencing of the human protozoan parasite Leishmania major is in progress. The driving forces behind the genome project are to identify genes with key cellular functions and new drug targets, to increase knowledge on mechanisms of drug resistance and to favor technology transfer to scientists from endemic countries. Sequencing of the genome is also aimed at the identification of genes that are expressed in the infectious stages of the parasite and in particular in the intracellular form of the parasite. Several protective antigens of Leishmania have been identified. In addition to these antigens, lysosomal cysteine proteinases (CPs) have been characterized in different strains of Leishmania and Trypanosoma, as new target molecules. Recently, we have isolated and characterized Type I (CPB) and Type II (CPA) cysteine proteinase encoding genes from L. major. The exact function of cysteine proteinases of Leishmania is not completely understood, although there are a few reports describing their role as virulence factors. One specific feature of CPB in Leishmania and other trypanosomatids, is the presence of a Cterminal extension (CTE) which is possibly indicative of conserved structure and function. Recently, we demonstrated that DNA immunization of genetically susceptible BALB / c mice, using a cocktail of CPB and CPA genes, induced long lasting protection against L. major infection. This review intends to give an overview of the current knowledge on genetic vaccination used against leishmaniasis and the importance of CP genes for such an approach.

Análisis bioinformáticos sobre la tecnología Hadoop

Desde el inicio del proyecto del genoma humano y su éxito en el año 2001 se han secuenciado genomas de multitud de especies. La mejora en las tecnologías de secuenciación ha generado volúmenes de datos con un crecimiento exponencial. El proyecto Análisis bioinformáticos sobre la tecnología Hadoop abarca la computación paralela de datos biológicos como son las secuencias de ADN. El estudio ha sido encauzado por la naturaleza del problema a resolver. El alineamiento de secuencias genéticas con el paradigma MapReduce.

A mucin like gene different from the previously reported members of the mucin like gene families is transcribed in Trypanosoma cruzi but not in Trypanosoma rangeli

Trypanosoma cruzi expresses mucin like glycoproteins encoded by a complex multigene family. In this work, we report the transcription in T. cruzi but not in T. rangeli of a mucin type gene automatically annotated by the T. cruzi genome project. The gene showed no nucleotide similarities with the previously reported T. cruzi mucin like genes, although the computational analysis of the deduced protein showed that it has the characteristic features of mucins: a signal peptide sequence, O-glycosylation sites, and glycosylphosphatidylinositol (GPI) anchor sequence. The presence in this gene of N- terminal and C- terminal coding sequences common to other annotated mucin like genes suggests the existence of a new mucin like gene family.

Trypanosoma cruzi ribosomal protein S4: characterization of its coding locus, analysis of transcripts, and antigenicity of the protein

Two allelic genomic fragments containing ribosomal protein S4 encoding genes (rpS4) from Trypanosoma cruzi (CL-Brener strain) were isolated and characterized. One allele comprises two complete tandem repeats of a sequence encoding an rpS4 gene. In the other, only one rpS4 gene is found. Sequence comparison to the accessed data in the genome project database reveals that our two-copy allele corresponds to a variant haplotype. However, the deduced aminoacid sequence of all the gene copies is identical. The rpS4 transcripts processing sites were determined by comparison of genomic sequences with published cDNA data. The obtained sequence data demonstrates that rpS4 genes are expressed in epimastigotes, amastigotes, and trypomastigotes. A recombinant version of rpS4 was found to be an antigenic: it was recognized by 62.5% of the individuals with positive serology for T. cruzi and by 93.3% of patients with proven chronic chagasic disease.