A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism. Almost all gene carriers can be detected by screening tests before the age of 40, but the nature and location of the predisposing gene are unknown. Simpson et al. recently reported preliminary evidence for linkage between the DNA probe p9-12A on chromosome 10 and MEN2A. We now report linkage between the MEN2A locus and the interstitial retinol-binding protein gene, which is located on chromosome 10p11.2-q11.2.     

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.     

Integration of cytogenetic landmarks into the draft sequence of the human genome

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.     

Gametocytogenesis by malaria parasites in continuous culture

Asexual proliferation of malaria parasites proceeds by multiplication of the parasites within red cells. Following rupture of the host cells the released merozoites re-invade other red cells. On re-invasion, a proportion of merozoites become, not asexual parasites but gametocytes, the sexual stages infective to the mosquito vectors. Conversion of asexual parasites to gametocytes occurs not only during natural infections but also in continuous in vitro culture as reported first by Trager and Jensen and by others. We showed previously that the proportion of early intra-erythrocytic stages (ring stages) of Plasmodium falciparum which developed into gametocytes in culture was influenced by culture conditions. Gametocyte formation was rare in conditions supporting rapid proliferation but frequent when parasite densisites were static. We now show that nearly 100% of ring stages develop into gametocytes in response to 1mM cyclic AMP in static cultures whereas in rapidly growing cultures few rings become gametocytes in response to cyclic AMP.     

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).