Genome-wide mapping with biallelic markers in Arabidopsis thaliana.

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.     

Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 相似文献   

Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia

We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.     

Abdominal obesity and metabolic syndrome

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.     

Vegetation and soil zonation associated with Juniperus pinchotii Sudw. trees

Herbaceous vegetation pattern and soil properties around individual Juniperus pinchotii Sudw. trees were studied on a grazed and a relict grassland in western Texas. Herb standing crop and soil samples were obtained under the canopy, at canopy edge, and beyond the canopy edge of three to five trees on each of four dates. Standing crop was lowest midway between the bole and canopy edge. Soil organic matter was highest under juniper canopies on both sites. Soil pH and P were not related to distance from tree bole on either site. Herbaceous pattern from under the canopy to canopy edge apparently depended primarily on individual tree size. However, trees had little influence on herbaceous vegetation pattern 3-5 m beyond canopy edge, a response attributed to distance-independent interaction between J. pinchotii and herbaceous vegetation. Given a shallow soil underlain by indurated caliche and tree densities ranging from 288 (relict size) to 2123 (grazed site) trees/ha, the interaction between J. pinchotii and herbaceous vegetation did not change over a distance of 3-5 m from tree canopy edge in our study area.     

水分和热胁迫对5种苗木生长及生物量的影响

以杉木、马尾松、花旗松、北美乔柏和扭叶松为对象，研究了水分和热胁迫对苗木生长期间生长和生物量的影响。结果表明：(1)水分胁迫对杉木、马尾松、花旗松、北美乔柏和扭叶松5个树种的苗高增长量和增长率均有显影响，但影响的程度因树种而异；(2)热胁迫对苗高增长量和增长率也有一定影响，但不如水分胁迫的影响大。热胁迫对北美乔柏和花旗松的苗高增长量及增长率有显影响，对其它树种的影响较小；(3)水分胁迫对杉苗生物量的影响不大，热胁迫对杉苗生物量指标的各部分干重有显影响；热和水分胁迫对马尾松苗木3个生物量指标均有显影响；热胁迫对花旗松、北美乔柏和扭叶松苗木生物量指标的影响均大于水分胁迫；(4)5个受试树种的根茎比受热和水分胁迫的影响都不大。     

La dualité des « Prolans » urinaires

Conclusions La préhypophyse sécrète deux hormones, l'auxogène et la crinogène. On peut, en détruisant ou éliminant le crinogène, obtenir des extraits à effet auxogène pur. L'urine de femme castrée ne contient que le principe auxogène: la lutéinisation, observée dans certains cas, est un effet secondaire dû à l'intervention de l'hypophyse de l'animal traité.L'urine de femme enceinte contient deux prolans: un principe crinogène identique à celui de l'hypophyse et agissant, comme ce dernier, directement sur l'ovaire; un principe hypophysotrope, stimulant l'hypophyse de l'animal — dans la mesure où elle est présente ou capable de réponse — et se traduisant dans l'ovaire par un effet auxogène de type physiologique.Les deux principes de l'UFE peuvent être séparés ou l'un peut être détruit avec conservation partielle de l'autre. Les taux des deux prolans varient d'une urine à l'autre, pour une même urine au cours de la gestation ou au cours du chauffage.L'existence de ces deux principes est importante à considérer lorsqu'on utilise, dans la pratique médicale, des extraits d'UFE qui sont, en réalité, des mélanges variables de deux hormones, dont les effets physiologiques et, par suite, les indications thérapentiques ne sont certainement pas les mémes.     

Variation in genome-wide mutation rates within and between human families

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans. Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.     

Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia

The past decade has seen great advances in unraveling the biological basis of hereditary ataxias. Molecular studies of spinocerebellar ataxias (SCA) have extended our understanding of dominant ataxias. Causative genes have been identified for a few autosomal recessive ataxias: Friedreich's ataxia, ataxia with vitamin E deficiency, ataxia telangiectasia, recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1 (refs. 6,7) and type 2 (ref. 8). Nonetheless, genes remain unidentified for most recessive ataxias. Additionally, pure cerebellar ataxias, which represent up to 20% of all ataxias, remain poorly studied with only two causative dominant genes being described: CACNA1A (ref. 9) and SPTBN2 (ref. 10). Here, we report a newly discovered form of recessive ataxia in a French-Canadian cohort and show that SYNE1 mutations are causative in all of our kindreds, making SYNE1 the first identified gene responsible for a recessively inherited pure cerebellar ataxia.