Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q.

We have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.     

Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: evidence for a founder effect in patients from Newfoundland.

An autosomal dominant syndrome of prolactinomas, carcinoids, and hyperparathyroidism was described in four Newfoundland kindreds in 1980 and in one kindred from the Pacific Northwest in 1983. Because this syndrome shares many features with multiple endocrine neoplasia type 1, the gene for which maps to proximal chromosome 11q, we performed linkage studies with chromosome 11 markers in prolactinoma families to determine whether the two genes map to the same location. All proximal chromosome 11q markers gave positive LOD scores, and no recombinants were seen with PYGM (LOD score 15.25, recombination fraction .0). All affected individuals from Newfoundland shared the same PYGM allele, providing evidence for a founder effect. The disease in the Pacific Northwest kindred cosegregated with a different PYGM allele.     

A new cloche design for elevating temperature in polar terrestrial ecosystems

A cloche design is described that is suitable for elevating temperature to simulate global warming in polar ecosystems. This cloche system was used in a manipulation experiment near Ny Ålesund, Spitsbergen, Svalbard. An average warming of 2.8 deg. C. was produced over a 60 day growing season, well within the range predicted by present climate models. The elevation effect is shown to be consistent over the diel cycle and throughout the short arctic summer season. Several advantages over previous designs of manipulation unit are highlighted.     

Factors limiting the distribution of Acyrthosiphon svalbardicum (Hemiptera: Aphididae) on Spitsbergen

The distribution of the high arctic aphid Acyrthosiphon svalbardicum was found to have a distinct limit in the Kongsfjorden area of Spitsbergen; the probability of site occupancy increased with distance from the fjord mouth and decreased with distance from the shore. Superimposed on this general distribution pattern, sites that cleared of snow early in the polar summer were more likely to be occupied by aphids. The phenology of the aphid was significantly affected by small changes in microclimate over distances of a few metres. The aphid only occurs in the warmer parts of the region, but laboratory cultures were successfully reared on plant material collected from colder regions that the aphid does not presently occupy. These observations suggest that the local distribution of A. svalbardicum is determined by summer thermal conditions. On a smaller scale, within patches where the aphids occurred, densities were higher on flowers and flowering shoots than on non-flowering shoots.     

Characterization of DNA adenine methylation mutants of Escherichia coli K12.

The phenotypic traits of 7 independently isolated dam mutants of Escherichia coli have been examined. The mutant strains differ from the wildtype in the following respects: (1) decreased DNA adenine methylase activity in vivo and in vitro; (2) a 14--85-fold increase in spontaneous mutability; (3) decreased survival after ultraviolet irradiation; (4) a 10--21-fold increase in spontaneous induction of lambda phage from lysogens; (5) a 3--17-fold increase in the level of recombination; and (6) inviability of double mutants containing dam- and recB- or recC-. Unmethylated fd phage chromosomes are able to replicate normally in dam- mutants. A mutant strain in which the dcm gene is deleted is viable, showing that the dcm gene product is dispensible for growth.     

Kinetics of formation of fibrin oligomers. II. Size distributions of ligated oligomers

Human fibrinogen was treated with thrombin in the presence of fibrinoligase (Factor XIIIa) and calcium ion at pH 8.5, ionic strength 0.45, and the ensuing polymerization was interrupted at various time intervals (t) both before and after the clotting time (t_c) by solubilization with a solution of sodium dodecylsulfate and urea. Aliquots of the solubilized protein were subjected to gel electrophoresis on polyacrylamide gels after disulfide reduction by dithiothreitol and on agarose gels without reduction. The degree of γ-γ ligation was determined from the former and the size distribution of ligated oligomers, for degree of polymerization x from 1 to 10, from the latter. In some experiments, thrombin was inhibited, after partial polymerization, by p-nitrophenyl-p′-guanidinobenzoate. From these, it was concluded that for thrombin concentration ?0.013 units/mL and fibrinoligase ?30 mg/L, oligomer assembly is rapid compared with peptide A release and ligation is rapid compared with assembly. Under these conditions, the theory of the first paper of this series describes rather well the time dependences of the degree of γ-γ ligation, the weight fractions of monomer and small oligomers, and the number- and weight-average degrees of polymerization after solubilization of the staggered overlapped assemblies, each of which splits to give two strands of end-to-end ligated oligomers. The theory assumes that the second A peptide is released by thrombin more rapidly than the first by a factor q, which, from the experimental data, is determined to be 16. The subsequent assembly into staggered overlapped oligomers follows the statistics of linear polycondesation taking into account the presence of both difunctional and monofunctional combining units. For higher thrombin or lower fibrinoligase concentrations, ligation fails to keep pace with oligomer assembly, and the size distributions after solubilization show a higher proportion of very small and a lower proportion of larger ligated oligomers, owing to separation of the staggered overlapped assemblies into smaller fragments.     

Comparative mapping of a gorilla-derived alpha satellite DNA clone on great ape and human chromosomes

We have isolated an alpha satellite DNA clone, pG3.9, from gorilla DNA. Fluorescence in situ hybridization on banded chromosomes under high stringency conditions revealed that pG3.9 identifies homologous sequences at the centromeric region of ten gorilla chromosomes, and, with few exceptions, also recognizes the homologous chromosomes in human. A pG3.9-like alphoid DNA is present on a larger number of orangutan chromosomes, but, in contrast, is present on only tow chromosomes in the chimpanzee. These results show that the chromosomal subsets of related alpha satellite DNA sequences may undergo different patterns of evolution.by J.B. Rattner     

A locus for familial hypertrophic cardiomyopathy is closely linked to the cardiac myosin heavy chain genes, CRI-L436, and CRI-L329 on chromosome 14 at q11-q12

We report that a gene responsible for familial hypertrophic cardiomyopathy (HC) is closely linked to the cardiac alpha and beta myosin heavy chain (MHC) genes on chromosome 14q11. We have recently shown that probe CRI-L436, derived from the anonymous DNA locus D14S26, detects a polymorphic restriction fragment that segregates with familial HC in affected members of a large Canadian family. Using chromosomal in situ hybridization, we have mapped CRI-L436 to chromosome 14 at q11-q12. Because the cardiac MHC genes also map to this chromosomal band, we have determined the genetic distances between the cardiac beta MHC gene, D14S26, and the familial HC locus. Data presented here show that these three loci are linked within 5 centimorgans on chromosome 14 at q11-q12. The possibility that defects in either the cardiac alpha or beta MHC genes are responsible for familial HC is discussed.     

Understanding the binding interaction between phenyl boronic acid P1 and sugars: determination of association and dissociation constants using S–V plots,steady‐state spectroscopic methods and molecular docking

Continuous monitoring of glucose and sugar sensing plays a vital role in diabetes control. The drawbacks of the present enzyme‐based sugar sensors have encouraged the investigation into alternate approaches to design new sensors. The popularity of fluorescence sensors is due to their ability to bind reversibly to compounds containing diol. In this study we investigated the binding ability of phenyl boronic acid P1 for monosaccharides and disaccharides (sugars) in aqueous medium at physiological pH 7.4 using steady‐state fluorescence and absorbance. P1 fluorescence was quenched due to formation of esters with sugars. Absorbance and fluorescence measurements led to results that indicated that the sugars studied could be ordered in terms of their affinity to P1, as stated: sucrose > lactose > galactose > xylose > ribose > arabinose. In each case, the slope of modified Stern–Volmer plots was nearly 1, indicating the presence of only a single binding site in boronic acids for sugars. Docking studies were carried out using Schrodinger Maestro v.11.2 software. The binding affinity of phenyl boronic acid P1 with periplasmic protein (PDB ID 2IPM and 2IPL) was estimated using GlideScore.     

Findings from the Peutz-Jeghers Syndrome Registry of Uruguay

Background

Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients.

Methods

Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed.

Results and discussion

25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000.

Conclusion

The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation.