Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study.

Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families. To investigate mutation origin and mutation-specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast/ovarian cancer families selected for having one of six recurrent BRCA1 mutations. Tests of both mutations and family-specific differences in age at diagnosis were not significant. A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect (P = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer, compared with 14% of affected women with the splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here, the individual mutations are estimated to have arisen 9-170 generations ago. In general, a high degree of haplotype conservation across the region was observed, with haplotype differences most often due to mutations in the short-tandem-repeat markers, although some likely instances of recombination also were observed. For several of the instances, there was evidence for multiple, independent, BRCA1 mutational events.     

An Evaluation of Genetic Heterogeneity in 145 Breast-Ovarian Cancer Families

The breast-ovary cancer–family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17ql2-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%–100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer–family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations.     

Do some deep‐sea,sediment‐dwelling species of harpacticoid copepods have 1000‐km‐scale range sizes?

The range sizes of sediment‐dwelling deep‐sea species are largely unknown. Such knowledge is important because a deep sea composed in large part of species with 100‐km‐scale ranges would be very different from one composed predominantly of species with 1000‐km‐scale ranges. For example, the total species richness would be much greater in the first case than in the second. As a step towards the determination of the distribution of species’ range sizes in the deep sea, we asked whether harpacticoid copepods (Crustacea) on the continental rise in the northeastern Pacific had 1000‐km‐scale range sizes. We chose harpacticoids because they occur widely in deep‐sea sediments and thus are a typical deep‐sea taxon. In addition, they have no pelagic stage in their life history, so they allow a conservative test of hypotheses about species’ range sizes. We used morphology and gene‐sequence data to assign individuals to species. At least 13.3% of the species we studied had 1000‐km‐scale ranges, raising the question of how these species maintain genetic continuity.     

Mapping ‘hydroscapes’ along the iso‐ to anisohydric continuum of stomatal regulation of plant water status

The concept of iso‐ vs. anisohydry has been used to describe the stringency of stomatal regulation of plant water potential (ψ). However, metrics that accurately and consistently quantify species’ operating ranges along a continuum of iso‐ to anisohydry have been elusive. Additionally, most approaches to quantifying iso/anisohydry require labour‐intensive measurements during prolonged drought. We evaluated new and previously developed metrics of stringency of stomatal regulation of ψ during soil drying in eight woody species and determined whether easily‐determined leaf pressure–volume traits could serve as proxies for their degree of iso‐ vs. anisohydry. Two metrics of stringency of stomatal control of ψ, (1) a ‘hydroscape’ incorporating the landscape of ψ over which stomata control ψ, and (2) the slope of the daily range of ψ as pre‐dawn ψ declined, were strongly correlated with each other and with the leaf osmotic potential at full and zero turgor derived from pressure–volume curves.     

The CEPH consortium primary linkage map of human chromosome 10

The first CEPH consortium map, that of chromosome 10, is presented. This primary linkage map contains 28 continuously linked loci defined by genotypes generated from CEPH family DNAs with 37 probe and enzyme combinations. Cytogenetic localization of some of the genetic markers indicates that the consortium map extends, at least, from 10p13 to 10q26. The order of loci on the consortium map agrees with the physical localization data. The female map spans 309 cM (206 cM if an approximation of interference is included in the mapping function used to construct the map), and the mean genetic distance of intervals is 11 cM (7 cM). Also presented are maps of chromosome 10 from each of five CEPH collaborating laboratories, based on genotypes for all relevant markers in the CEPH database. The CEPH consortium map of chromosome 10 should be useful for localization of any gene of interest falling within the span covered. The genotypes in the chromosome 10 consortium map database are now available to the scientific community.     

Immediate-early mRNA-2 of herpes simplex viruses types 1 and 2 is unspliced: conserved sequences around the 5' and 3' termini correspond to transcription regulatory signals

Nuclease S1 and exonuclease VII analyses of immediate-early (IE) mRNA-2 of herpes simplex viruses types 1 and 2 (HSV-1, HSV-2) show them to be unspliced and of similar length. The DNA sequences around the 5' and 3' termini have been determined. Comparison of the sequences around the 5' ends reveals several common features. (1) Four discrete blocks of upstream homology which are precisely colinear with respect to the 5' termini of the mRNAs; the blocks include the 'TATA' box, a G-C rich sequence and a sequence (AATTAAATACAT) which may be involved in the coordinate induction of the IE class of genes. (2) Several copies of the sequence CCCCGCCC, found in different upstream positions in HSV-1 and HSV-2, which may be important in the expression of a wide variety of eukaryotic genes. (3) Potential hairpin structures in the region of the 5' termini which are present at similar locations in HSV-1 and HSV-2. Sequence comparison around the 3' termini of IEmRNA-2 reveals high homology at the proposed C-terminus of the polypeptide.     

Localization of crystals in diseased oats treated with uranyl acetate

Uranyl acetate, a suppressor of victorin-induced electrolyte leakage in oat leaves when applied together with, or before, victorin, also suppressed victorin-induced changes in ultra-structure. Uranyl crystallized in cell walls and near the plasmalemma of vascular cells, but was excluded from the protoplasm. Fewer crystals occurred near the plasmalemma when leaves were allowed to take up uranyl and victorin simultaneously than when uranyl alone was absorbed, but deposition in cell walls was similar in the two treatments. No differences in crystal distribution were found in uranyl-treated leaves which subsequently took up either water or victorin. The most striking effect of prolonged exposure to uranyl was increased vesicular activity in the protoplasm, formation of complex concentric membranes, and tonoplast damage. Following victorin treatment, uranyl post-treatment was ineffective in suppressing electrolyte leakage or preserving normal cellular ultrastructure. More severe ultrastructural damage was found in victorintreated leaves after uranyl post-treatments than after post-treatment with water, a result of victorin-induced damage which facilitates uranyl entry into the protoplasm.