1998～2003年:美国人类基因组计划的新目标

在1993～1998的5年计划中，人类基因组计划成功地完成了既定的所有重要目标。我们提出了一项新的1998～2003年的计划，人类DNA测序是其重中之重。一项旨在2003年底前完成整个人类基因组的测序的雄心勃勃的计划已经投入实施、在此过程中，一幅人类基因组序列的“工作草图”将在2001年底产生。此项计划的目标还包括：测序技术的开发；人类基因组序列变异的研究；功能基因组学技术的开发；完成美丽隐杆线虫和黑腹果蝇的测序并启动小鼠基因组的测序；研究基因组研究带来的伦理学、法律和社会学影响；生物信息学和计算生物学研究；以及基因组科学家的培养。     

Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays.

Here we report the application of high-density oligonucleotide array (DNA chip)-based analysis to determine the distant history of single nucleotide polymorphisms (SNPs) in current human populations. We analysed orthologues for 397 human SNP sites (identified in CEPH pedigrees from Amish, Venezuelan and Utah populations) from 23 common chimpanzee, 19 pygmy chimpanzee and 11 gorilla genomic DNA samples. From this data we determined 214 proposed ancestral alleles (the sequence found in the last common ancestor of humans and chimpanzees). In a diverse human population set, we found that SNP alleles with higher frequencies were more likely to be ancestral than less frequently occurring alleles. There were, however, exceptions. We also found three shared human/pygmy chimpanzee polymorphisms, all involving CpG dinucleotides, and two shared human/gorilla polymorphisms, one involving a CpG dinucleotide. We demonstrate that microarray-based assays allow rapid comparative sequence analysis of intra- and interspecies genetic variation.     

Trading zones and interactional expertise

The phrase ‘trading zone’ is often used to denote any kind of interdisciplinary partnership in which two or more perspectives are combined and a new, shared language develops. In this paper we distinguish between different types of trading zone by asking whether the collaboration is co-operative or coerced and whether the end-state is a heterogeneous or homogeneous culture. In so doing, we find that the voluntary development of a new language community—what we call an inter-language trading zone—represents only one of four possible configurations. In developing this argument we show how different modes of collaboration result in different kinds of trading zone, how different kinds of trading zone may be ‘nested’ inside each other and discuss how a single collaboration might move between different kinds of trading zone over time. One implication of our analysis is that interactional expertise is a central component of at least one class of trading zone.     

Experiments with interactional expertise

‘Interactional expertise’ is developed through linguistic interaction without full scale practical immersion in a culture. Interactional expertise is the medium of communication in peer review in science, in review committees, and in interdisciplinary projects. It is also the medium of specialist journalists and of interpretative methods in the social sciences. We describe imitation game experiments designed to make concrete the idea of interactional expertise. The experiments show that the linguistic performance of those well socialized in the language of a specialist group is indistinguishable from those with full blown practical socialization but distinguishable from those who are not well socialized. The imitation game can also be used to indicate whether an individual can enter an esoteric domain and master the interactional expertise, a skill required by interpretative sociologists of science, anthropologists, ethnographers, and the like.     

运用RAPD技术鉴定澳大利亚油橄榄品种的研究

由于早期引种记录的丢失、栽培品种的错命名和重命名、品种间的杂交等原因，澳洲现有的油橄榄品种形态变化较大，同名异物和同物异名现象比较普遍，使品种间的鉴定十分困难．运用随机扩增多态DNA技术，在筛选引物的基础上，分别对2种待鉴定样品和9个已知油橄榄品种的RAPD指纹进行比较分析，经UPG—MA聚类分析，在鉴定待测样品上取得了理想效果．     

Exclusion of DNA changes in the beta-subunit of the c-GMP phosphodiesterase gene as the cause for Huntington's disease.

To identify expressed sequences within candidate regions for the Huntington's disease (HD) gene in 4p16.3, we isolated the gene encoding the beta subunit of the human cGMP phosphodiesterase (PDEB). We formally assessed this as a candidate gene for HD based on it's expression in brain, the demonstration of linkage disequilibrium between intragenic DNA markers and HD, and the demonstration that mice with a mutation in this gene have a reduction of neurons in particular brain regions. We investigated all 22 exons of PDEB and 5'-flanking region for point mutations in 16 HD patients of different ethnic origins using single strand conformational polymorphism analysis. The underlying DNA changes found initially exclusively in HD patients were excluded as the cause for HD.