Showing papers by "Wellcome Trust Sanger Institute published in 2001"

Initial sequencing and analysis of the human genome.

Abstract: 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.

Cancer and genomics

Abstract: Identification of the genes that cause oncogenesis is a central aim of cancer research. We searched the proteins predicted from the draft human genome sequence for paralogues of known tumour suppressor genes, but no novel genes were identified. We then assessed whether it was possible to search directly for oncogenic sequence changes in cancer cells by comparing cancer genome sequences against the draft genome. Apparently chimaeric transcripts (from oncogenic fusion genes generated by chromosomal translocations, the ends of which mapped to different genomic locations) were detected to the same degree in both normal and neoplastic tissues, indicating a significant level of false positives. Our experiment underscores the limited amount and variable quality of DNA sequence from cancer cells that is currently available.

Plant protein families and their relationships to food allergy

Abstract: The analysis of plant proteins has a long and distinguished history, with work dating back over 250 years. Much of the work has focused on seed proteins, which are important in animal nutrition and food processing. Early studies classified plant proteins into groups based on solubility ('Osborne fractions') or protein function. More recently, families have been defined based on stuctural and evolutionary relationships. One of the most widespread groups of plant proteins is the prolaminin superfamily, which comprises cereal seed storage proteins, a range of low-molecular-mass sulphur-rich proteins (many of which are located in seeds) and some cell wall glycoproteins. This superfamily includes several major types of plant allergen: non-specific lipid transfer proteins, cereal seed inhibitors of alpha-amylase and/or trypsin, and 2 S albumin storage proteins of dicotyledonous seeds.

A SNP Resource for Human Chromosome 22: Extracting Dense Clusters of SNPs From the Genomic Sequence

Abstract: The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR–RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]

Characterization of Clustered MHC-Linked Olfactory Receptor Genes in Human and Mouse

Abstract: Olfactory receptor genes (ORs) were first identified in rat olfactory epithelium as small, intronless genes with easily identifiable consensus motifs in conserved domains of the predicted seven transmembrane (7-TM) structure (Buck and Axel 1991). This work stimulated much interest in understanding the molecular basis of olfaction, leading to a large number of ORs being identified. ORs are best known for their involvement in the perception of odors, which is accomplished through OR expression in two anatomically and functionally different organs within the nose: the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). In general, ORs expressed in the MOE are believed to recognize environmental odors (conscious odor perception), whereas ORs expressed in the VNO are believed to recognize odors such as pheromones (subconscious odor perception). However, two recent studies suggest that most of the VNO-type 1 ORs (V1Rs) are nonfunctional pseudogenes in humans (Giorgi et al. 2000; Rodriguez et al. 2000). Nonolfaction-associated OR function such as cell-cell recognition in embryogenesis has also been suggested (Dreyer 1998). For recent reviews on the molecular and cellular biology of ORs, see the special Science issue of October 27, 1999, on olfaction (Science vol. 286; Mombaerts 1999a,b). Public databases currently hold over 600 OR and OR-like genes and pseudogenes, from invertebrates such as Caenorhabditis elegans and Drosophila melanogaster to complex vertebrates, including more than 200 from Homo sapiens. However, the analysis of these ORs has somehow been hampered because only partial sequences are available for most of them (at least for the mammalian ORs). This shortcoming is largely the result of the quick but imperfect approach to identify new ORs by degenerate PCR, and it will soon be corrected as more genomic sequences become available. A recent genome-wide survey revealed that MOE-type ORs are present on most human chromosomes (Rouquier et al. 1998). The fact that ORs occur in clusters rather than being randomly distributed was recognized early on (Ben-Arie et al. 1994), and a combination of repeated single gene and block duplications was proposed as the underlying mechanism (Lancet and Ben-Arie 1993; Glusman et al. 1996, 2000; Sullivan et al. 1996; Trask et al. 1998a,b). The existence of major histocompatibility complex (MHC)-linked ORs on human chromosome 6 was first discovered in 1995 (Fan et al. 1995). Using a cDNA selection approach, several cDNAs were identified (including FAT11) and mapped telomeric of the MHC. Together with the recently published sequence of the classical MHC (The MHC Sequencing Consortium 1999), the OR cluster reported here forms over 4.5 Mb of contiguous genomic sequence. The region including the OR cluster has previously been shown to be in strong linkage disequilibrium with the MHC (although possibly not in all haplotypes) and has been proposed to be part of the extended MHC (Malfroy et al. 1997; Stephens et al. 1999). This raises the possibility that these ORs are not only physically linked to the MHC but also may have some functional association (e.g., mate selection) with genes of the complex (Ehlers et al. 2000; Ziegler et al. 2000a). Therefore, we have sequenced the human MHC-linked OR cluster and discuss here our findings in comparison with our preliminary data from the orthologous murine OR cluster.