Linkage disequilibrium in the human genome

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.     

行波：数学推理的元极导航

本书是《剑桥理论计算科学专论》丛书的第56卷。自从20世纪50年代起，自动化理论证明成为一个活跃的研究领域。在该领域中的研究人员开始着手处理类似人类的自动化推理。在20世纪60年代和70年代，人们对自动化理论证明的兴趣增加了，这是由于理论进展的驱动。例如归纳的开发以及对程序验证的兴趣增加。     

Isotopic enhancements of 17O and 18O from solar wind particles in the lunar regolith

Differences in isotopic abundances between meteorites and rocks on Earth leave unclear the true composition of the gas out of which the Solar System formed. The Sun should have preserved in its outer layers the original composition, and recent work has indicated that the solar wind is enriched in 16O, relative to Earth, Mars and bulk meteorites. This suggests that self-shielding of CO due to photo-dissociation, which is a well understood process in molecular clouds, also led to evolution in the isotopic abundances in the early Solar System. Here we report measurements of oxygen isotopic abundances in lunar grains that were recently exposed to the solar wind. We find that 16O is underabundant, opposite to an earlier finding based on studies of ancient metal grains. Our result, however, is more difficult to understand within the context of current models, because there is no clear way to make 16O more abundant in Solar System rocks than in the Sun.     

Change in compatibility after microinjection of cytoplasm in amoebae

Summary A cytoplasmic fraction from D32, a clone of amoebae derived fromAmoeba proteus injected with cytoplasm fromA. discoides, inhibited cell division inA. proteus but not inA. discoides indicating a permanent change with respect to compatibility.     

Photoreactivable sectors and the systematics of the genusPichia

Zusammenfassung Es wird der Beweis erbracht, dass photoreaktivierungsfähige Sektoren von Zellen einen zusätzlichen Affinitätsparameter zwischer Hefen der GattungenHansenula undPichia bilden und vielleicht wertvolle Daten für die endgültige Erschliessung der intragenerischen Phylogenie derPichia liefern.

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These studies were aided in part by a contract No. AT (11-1)-1772 with the U.S. Atomic Energy Commission.     

Characterization of single-nucleotide polymorphisms in coding regions of human genes.

A major goal in human genetics is to understand the role of common genetic variants in susceptibility to common diseases. This will require characterizing the nature of gene variation in human populations, assembling an extensive catalogue of single-nucleotide polymorphisms (SNPs) in candidate genes and performing association studies for particular diseases. At present, our knowledge of human gene variation remains rudimentary. Here we describe a systematic survey of SNPs in the coding regions of human genes. We identified SNPs in 106 genes relevant to cardiovascular disease, endocrinology and neuropsychiatry by screening an average of 114 independent alleles using 2 independent screening methods. To ensure high accuracy, all reported SNPs were confirmed by DNA sequencing. We identified 560 SNPs, including 392 coding-region SNPs (cSNPs) divided roughly equally between those causing synonymous and non-synonymous changes. We observed different rates of polymorphism among classes of sites within genes (non-coding, degenerate and non-degenerate) as well as between genes. The cSNPs most likely to influence disease, those that alter the amino acid sequence of the encoded protein, are found at a lower rate and with lower allele frequencies than silent substitutions. This likely reflects selection acting against deleterious alleles during human evolution. The lower allele frequency of missense cSNPs has implications for the compilation of a comprehensive catalogue, as well as for the subsequent application to disease association.     

New evidence that growth in 3T3 cell cultures is a diffusion-limited process

When a confluent culture of 3T3 cells is wounded, new growth occurs at the wound margins. This indicates that the suppression of growth in the intact confluent sheet is under local control, a phenomenon known as 'topoinhibition', and it has been suggested that intercellular contact is responsible. An alternative explanation for topoinhibition is possible, however, namely that a soluble factor necessary for growth is locally depleted from the medium by cells so that each cell in a confluent sheet normally receives an insufficient supply and its growth is inhibited. Here we show that the pattern of release from topoinhibition in a wounded culture can be distorted simply by inducing a gentle laminar flow of medium across the wound. Growth remains suppressed at the upstream margin of the wound despite the reduced level of intercellular contact at wound edges. We conclude that the signal for topoinhibition is carried by the flow as would be predicted if it were the local depletion of growth factor.     

A close halo of large transparent grains around extreme red giant stars

An intermediate-mass star ends its life by ejecting the bulk of its envelope in a slow, dense wind. Stellar pulsations are thought to elevate gas to an altitude cool enough for the condensation of dust, which is then accelerated by radiation pressure, entraining the gas and driving the wind. Explaining the amount of mass loss, however, has been a problem because of the difficulty of observing tenuous gas and dust only tens of milliarcseconds from the star. For this reason, there is no consensus on the way sufficient momentum is transferred from the light from the star to the outflow. Here we report spatially resolved, multiwavelength observations of circumstellar dust shells of three stars on the asymptotic giant branch of the Hertzsprung-Russell diagram. When imaged in scattered light, dust shells were found at remarkably small radii (less than about two stellar radii) and with unexpectedly large grains (about 300 nanometres in radius). This proximity to the photosphere argues for dust species that are transparent to the light from the star and, therefore, resistant to sublimation by the intense radiation field. Although transparency usually implies insufficient radiative pressure to drive a wind, the radiation field can accelerate these large grains through photon scattering rather than absorption--a plausible mass loss mechanism for lower-amplitude pulsating stars.     

A method for relocation of specified regions in tissue culture dishes

Summary An apparatus and method are described which facilitate the rapid and accurate visual relocation of specified areas within ordinary, circular, plastic petri-dishes.     

Geological and chronological evidence of Indo-Chinese strike-slip movement in the Altyn Tagh fault zone

A set of granitic and amphibole mylonite are exposed in the Altyn Tagh fault zone. The preliminary study shows that these rocks are the product of the syntectonic anatexis in the process of the left-lat- eral strike-slip shear, and are the result of the ductile transpression. There are two types of zircon sorted from the mylonite formed with synshear anatexis. Among them, one is the anatectic long columnar zircon and another is the residual metamorphic sub-rounded columnar zircon. Two groups of age for single zircon measured by ion microprobe (SHRIMP) are obtained: one is 461-547 Ma for the sub-rounded columnar residual metamorphic zircon, and the other is 239-244 Ma for the long-columnar anatectic zircon. This type of zircon is directionally spread in rock, and the long axis direction of its crystal is identical to that of stretching lineation, representing the direction of tectonic stress in the process of the strike-slip. 40Ar-39Ar age of the directional growth hornblende in the same mylonite sample measured is 223-226 Ma. The above geological and chronological data prove that the syntectonic anatexis occurred during Indo-Chinese Epoch, showing that the strong strike-slip movement occurred in the Altyn Tagh fault zone at least as early as Indo-Chinese Epoch.