Regional localisations and linkage relationships of seven RFLPs and myotonic dystrophy on chromosome 19

Summary We have studied the genetic linkage relationships of seven DNA polymorphisms on chromosome 19, with each other and with the myotonic dystrophy locus. The DNA sequences were localised to various regions of the chromosome using translocations in somatic cell hybrids. These results provide the basis for a linkage map of most of chromosome 19, and suggest that the myotonic dystrophy locus is close to the centromere.     

An experimental setup for the measurement of forces on a human cadaveric foot during inversion

An experimental setup was developed for statically measuring seven vertical and three horizontal reaction forces on the foot. In the setup, the leg can be simultaneously loaded (1) by a vertical force, (2) by an externally applied axial moment, and (3) by simulated muscle forces. The foot is free to invert under influence of the external loads. Statical analysis and test experiments were used for evaluation. The setup can be used in combination with Roentgen photogrammetry to measure bone positions simultaneously with forces.     

Low codon bias and high rates of synonymous substitution in Drosophila hydei and D. melanogaster histone genes

We have evaluated codon usage bias in Drosophila histone genes and have obtained the nucleotide sequence of a 5,161-bp D. hydei histone gene repeat unit. This repeat contains genes for all five histone proteins (H1, H2a, H2b, H3, and H4) and differs from the previously reported one by a second EcoRI site. These D. hydei repeats have been aligned to each other and to the 5.0-kb (i.e., long) and 4.8-kb (i.e., short) histone repeat types from D. melanogaster. In each species, base composition at synonymous sites is similar to the average genomic composition and approaches that in the small intergenic spacers of the histone gene repeats. Accumulation of synonymous changes at synonymous sites after the species diverged is quite high. Both of these features are consistent with the relatively low codon usage bias observed in these genes when compared with other Drosophila genes. Thus, the generalization that abundantly expressed genes in Drosophila have high codon bias and low rates of silent substitution does not hold for the histone genes.      

Warfarin-resistance genotype determination in the Norway rat, Rattus norvegicus

The 2-stage determination is based on changes in blood coaggulation activity brought about both by the administration of warfarin in conjunction with vitamin K1 epoxide and by feeding a vitamin K-free diet for 4 days. When it was applied to laboratory-bred rats of known warfarin-resistance genotype, 35/35 homozygous susceptible, 44/44 homozygous resistant and 131/133 heterozygous rats were correctly classified. This method was equally effective in identifying the genotype of wild rats carrying the warfarin-resistance gene, Rw2. The procedure is rapid and accurate.     

Distances that perfectly mislead

Given a collection of discrete characters (e.g., aligned DNA sites, gene adjacencies), a common measure of distance between taxa is the proportion of characters for which taxa have different character states. Tree reconstruction based on these (uncorrected) distances can be statistically inconsistent and can lead to trees different from those obtained using character-based methods such as maximum likelihood or maximum parsimony. However, in these cases the distance data often reveal their unreliability by some deviation from additivity, as indicated by conflicting support for more than one tree. We describe two results that show how uncorrected (and miscorrected) distance data can be simultaneously perfectly additive and misleading. First, multistate character data can be perfectly compatible and define one tree, and yet the uncorrected distances derived from these characters are perfectly treelike (and obey a molecular clock), only for a completely different tree. Second, under a Markov model of character evolution a similar phenomenon can occur; not only is there statistical inconsistency using uncorrected distances, but there is no evidence of this inconsistency because the distances look perfectly treelike (this does not occur in the classic two-parameter Felsenstein zone). We characterize precisely when uncorrected distances are additive on the true (and on a false) tree for four taxa. We also extend this result to a more general setting that applies to distances corrected according to an incorrect model.     

Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome) is linked to chromosome 9q34

Ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome [AOA]; MIM 208920) is an autosomal recessive disorder characterized by ataxia, oculomotor apraxia, and choreoathetosis. These neurological features resemble those of ataxia-telangiectasia (AT), but in AOA there are none of the extraneurological features of AT, such as immunodeficiency, neoplasia, chromosomal instability, or sensitivity to ionizing radiation. It is unclear whether these patients have a true disorder of chromosomal instability or a primary neurodegenerative syndrome, and it has not been possible to identify the defective gene in AOA, since the families have been too small for linkage analysis. We have identified a new family with AOA, and we show that the patients have no evidence of chromosomal instability or sensitivity to ionizing radiation, suggesting that AOA in this family is a true primary cerebellar ataxia. We have localized the disease gene, by linkage analysis and homozygosity mapping, to a 15.9-cM interval on chromosome 9q34. This work will ultimately allow the disease gene to be identified and its relevance to other types of autosomal recessive cerebellar ataxias to be determined.     

Characterization of a protein-based adhesive elastomer secreted by the Australian frog Notaden bennetti

When provoked, Notaden bennetti frogs secrete an exudate which rapidly forms a tacky elastic solid ("frog glue"). This protein-based material acts as a promiscuous pressure-sensitive adhesive that functions even in wet conditions. We conducted macroscopic tests in air to assess the tensile strength of moist glue (up to 78 +/- 8 kPa) and the shear strength of dry glue (1.7 +/- 0.3 MPa). We also performed nanomechanical measurements in water to determine the adhesion (1.9-7.2 nN or greater), resilience (43-56%), and elastic modulus (170-1035 kPa) of solid glue collected in different ways. Dry glue contains little carbohydrate and consists mainly of protein. The protein complement is rich in Gly (15.8 mol %), Pro (8.8 mol %), and Glu/Gln (14.1 mol %); it also contains some 4-hydroxyproline (4.6 mol %) but no 5-hydroxylysine or 3,4-dihydroxyphenylalanine (L-Dopa). Denaturing gel electrophoresis of the glue reveals a characteristic pattern of proteins spanning 13-400 kDa. The largest protein (Nb-1R, apparent molecular mass 350-500 kDa) is also the most abundant, and this protein appears to be the key structural component. The solid glue can be dissolved in dilute acids; raising the ionic strength causes the glue components to self-assemble spontaneously into a solid which resembles the starting material. We describe scattering studies on dissolved and solid glue and provide microscopy images of glue surfaces and sections, revealing a porous interior that is consistent with the high water content (85-90 wt %) of moist glue. In addition to compositional similarities with other biological adhesives and well-known elastomeric proteins, the circular dichroism spectrum of dissolved glue is almost identical to that for soluble elastin and electron and scanning probe microscopy images invite comparison with silk fibroins. Covalent cross-linking does not seem to be necessary for the glue to set.     

Identification of plant microRNA homologs

MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that regulate gene and protein expression in plants and animals. MiRNAs have so far been identified mostly by specific cloning of small RNA molecules, complemented by computational methods. We present a computational identification approach that is able to identify candidate miRNA homologs in any set of sequences, given a query miRNA. The approach is based on a sequence similarity search step followed by a set of structural filters.