Bruno Chauvel

Linkage disequilibrium and extended haplotypes in the HLA-A to D6S105 region: implications for mapping the hemochromatosis gene (HFE).

The hemochromatosis gene (HFE) maps to 6p21.3, in close linkage with the HLA Class I genes. Linkage disequilibrium (LD) studies were designed to narrow down the most likely candidate region for HFE, as an alternative to traditional linkage analysis. However, both the HLA-A and D6S105 subregions, which are situated 2–3 cM and approximately 3 Mb apart, have been suggested to contain HFE. The present report extends our previous study based upon the analysis of a large number of HFE and normal chromosomes from 66families of Breton ancestry. In addition to the previously used RFLP markers spanning the 400-kb surrounding HLA-A, we examined three microsatellites: D6S510, HLA-F, and D6S105. Our combined data not only confirm a peak of LD at D6S105, but also reveal a complex pattern of LD over the i82 to D6S105 interval. Within our ethnically well-defined population of Brittany, the association of HFE with D6S105 is as great as that with HLA-A, while the internal markers display a lower LD. Fine haplotype analysis enabled us to identify two categories of haplotypes segregating with HFE. In contrast to the vast majority of normal haplotypes, 50% of HFE haplotypes are completely conserved over the HLA-A to D6S105 interval. These haplotypes could have been conserved through recombination suppression, selective forces and/or other evolutionary factors. This particular haplotypic configuration might account for the apparent inconsistencies between genetic linkage and LD data, and additionally greatly complicates positional cloning of HFE through disequilibrium mapping.

Human release factor eRF1: structural organisation of the unique functional gene on chromosome 5 and of the three processed pseudogenes

In lower and higher eukaryotes, a family of tightly related proteins designated eRF1 (for eukaryotic release factor 1) catalyses termination of protein synthesis at all three stop codons. The human genome contains four eRF1 homologous sequences localised on chromosomes 5, 6, 7 and X. We report here the cloning and the structural analysis of the human eRF1 gene family. It appears that the gene located on chromosome 5 alone is potentially functional, whereas the other three sequences resemble processed pseudogenes. This is the first description of the structural organisation of the human eRF1 gene, which has been remarkably conserved during evolution and which is essential in the translation termination process.

Physical map of the HLA-A/HLA-F subregion and identification of two new coding sequences.

As part of an effort to characterize the hemochromatosis gene, we selected three non-chimeric yeast artificial chromosomes (YACs) overlapping with the YAC B30 previously described and forming an 800 kilobase contig covering theHLA-A/HLA-F region. The precise physical map of these YACs and of the corresponding genomic region were established. Nine concentrated sites of CpG cutter elements, potentially HTF islands, were mapped. In addition, several probes have been generated as tools for mapping and examining transcripts produced in the region. This allowed for the characterization and localization of two new coding sequences, provisionally namedHCG (for hemochromatosis candidate gene) and numberedVIII andIX.

Decreases in Crop Production by Non-native Weeds, Pests, and Pathogens

The worldwide trade of agricultural products and high levels of disturbance and fertilisation make arable lands particularly vulnerable to biological invasions. Clearing for the development of arable land has been an unprecedented event that created a new and more homogeneous habitat which allowed many species to spread to become (sub)cosmopolitan weeds, pests, and pathogens. Through competition for light, water, and nutrients (weeds), or destruction of plant tissue (pests and pathogens), harmful organisms can potentially reduce crop yield by 10–40 % on average. Historically, some non-native species produced spectacular invasions and caused incalculable damage by annihilating crop production at large scales: for example, potato late blight, Phytophthora infestans, which was one of the factors causing the Irish Potato Famine, and the American vine phylloxera, Daktulosphaira vitifoliae, which devastated vineyards across the whole of Europe. Nowadays, it is estimated that non-native weeds, pests, and pathogens cause as much as US

Analysis of 160 CF chromosomes: detection of a novel mutation in exon 20.

248 billion in annual losses to world agriculture, making this the sector most affected by the introduction of non-native species. The use of pesticides has long protected crop yield satisfactorily. However, because of the undesirable side effects that may be associated with pesticide use (e.g., development of resistant biotypes and water pollution), more integrated approaches to combat invasive species are needed, including prevention (phytosanitary control) and cropping systems with higher potential for ecological regulation.

Haemochromatosis and HLA-H.

The cystic fibrosis (CF) gene has been cloned and a major mutation identified (ΔF508). This 3-bp deletion has been found in approximately 70% of CF chromosomes. We have used the strategy of denaturing gradient gel electrophoresis followed by direct sequencing of the polymerase chain reaction products, in order to detect other mutations in exons 10, 11 and 20 of the CF transmembrane conductance regulator gene. A new mutation, F1286-S, was found in exon 20. It involves a nucleotide change of T→C at nucleotide 3989 and changes a phenylalanine into serine at position 1286 of the protein.