Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles

We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.     

Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies

Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin. Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to new therapeutic approaches. Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006     

植物标签技术

传统的正向遗传学主要用于克隆表型或功能已确定的基因。转座子标签突变体可用随机标签法从带有活性转座子的自交后代中筛选得到,或用定向标签法从杂交一代中筛选得到,即用目的基因的隐性突变统合体与具高度活性转座号的统合体杂交,极大多数的FI个体为正常表型,但其中会有极少量的表现隐性性状的转庄子插入突变体。正向基因标签和克隆法在利用异源和低拷贝数品系时尤其有用。采用反向fCR或热不对称交替PCR（TAIL－PCR）且很容易从单拷贝或低拷贝数品系中获得插入于两侧的基因组序列。TAIL－PCR由三轮连续的半巢式PCR组成,所…     

Mixtures of Autoregressions with an Improper Component for Panel Data

An EM algorithm for fitting mixtures of autoregressions of low order is constructed and the properties of the estimators are explored on simulated and real datasets. The mixture model incorporates a component with an improper density, which is intended for outliers. The model is proposed as an alternative to the search for the order of a single-component autoregression. The methods can be adapted to other patterns of dependence in panel data. An application to the monthly records of income of the outlets of a retail company is presented.     

Transthyretin: a review from a structural perspective

Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism of amyloid formation and detecting the variant gene in individuals at risk. Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001     

Equilibrating metal-oxide cluster ensembles for oxidation reactions using oxygen in water.

Although many enzymes can readily and selectively use oxygen in water-the most familiar and attractive of all oxidants and solvents, respectively-the design of synthetic catalysts for selective water-based oxidation processes utilizing molecular oxygen remains a daunting task. Particularly problematic is the fact that oxidation of substrates by O2 involves radical chemistry, which is intrinsically non-selective and difficult to control. In addition, metallo-organic catalysts are inherently susceptible to degradation by oxygen-based radicals, while their transition-metal-ion active sites often react with water to give insoluble, and thus inactive, oxides or hydroxides. Furthermore, pH control is often required to avoid acid or base degradation of organic substrates or products. Unlike metallo-organic catalysts, polyoxometalate anions are oxidatively stable and are reversible oxidants for use with O2 (refs 8,9,10). Here we show how thermodynamically controlled self-assembly of an equilibrated ensemble of polyoxometalates, with the heteropolytungstate anion [AIVVW11O40]6- as its main component, imparts both stability in water and internal pH-management. Designed to operate at near-neutral pH, this system facilitates a two-step O2-based process for the selective delignification of wood (lignocellulose) fibres. By directly monitoring the central Al atom, we show that equilibration reactions typical of polyoxometalate anions keep the pH of the system near 7 during both process steps.     

Individual recognition in mice mediated by major urinary proteins.

The ability to recognize individuals is essential to many aspects of social behaviour, such as the maintenance of stable social groups, parent-offspring or mate recognition, inbreeding avoidance and the modulation of competitive relationships. Odours are a primary mediator of individuality signals among many mammals. One source of odour complexity in rodents, and possibly in humans, resides in the highly polymorphic major histocompatibility complex (MHC). The olfactory acuity of mice and rats allows them to distinguish between the urinary odours of congenic strains differing only in single genes within the MHC, although the chemical mediators or odorants are unknown. However, rodent urine also contains a class of proteins, termed major urinary proteins (MUPs), that bind and release small volatile pheromones. We have shown that the combinatorial diversity of expression of MUPs among wild mice might be as great as for MHC, and at protein concentrations a million times higher. Here we show in wild house mice (Mus domesticus) that urinary MUPs play an important role in the individual recognition mechanism.