Numerous potentially functional but non-genic conserved sequences on human chromosome 21

The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.     

人染色体17q12区雨330kb范围内表达顺序的筛选

用定位于人染色体17q12区带的长约330kbYAC克隆500D09（取自法国人类多态性研究中心YAC库）作为杂交探针，筛选人骨髓、胎脑、胎肾、骨骼肌和睾丸等五种组织的cDNA库（2×105～3×105pfu／库），从中获得102个初级阳性克隆．初级克隆经PCR扩增，分别与人基因组DNA、酵母基因组DNA和人rDNA探针作dotblot杂交分析，排除其中假阳性克隆后，复筛得到32个候选克隆．对其中2个候选克隆B4511和S5511分别测定143bp和147bp序列．经查新和同源性分析，这两个片段与已知基因的同源性均小于50％，提示它们可能是来自于新基因的表达顺序．     

人类显带染色体的图象分割的研究

染色体图象分割是染色体图象分析与识别的重要内容之一。文中提出了关于一场景多个人类显带染色体的自动分割算法ｍｏｓｇｔｅｔ，该算法充分考虑了每个视野中分割目标（染色体）的数量大以及人类显带染色体被明暗交迭的带纹分割为若干不连续的片段等特点，自动调整分割阈值，既保证了完整地分割单条显带染色体，又能快速分割出一幅图象中９６％～１００％的染色体。该分割算法被有效地运用在自行开发的人类显带染色体的图象分析与识别系统中。     

Regional localization of sex-specific Bkm-related sequences on proximal chromosome 17 of mice

Development and fertility in the mouse are known to be influenced by loci mapped to the T/t complex of chromosome 17. Recent evidence suggests that one or more genes near this region may also be associated with sex determination. Washburn and Eicher recently reported partial to complete sex reversal with the Thp deletion on some genetic backgrounds and suggest that this result may be due to a primary sex-determining locus (Tas) that is closely linked to, or a part of, the T locus. Sex-specific, Bkm (banded Krait minor satellite DNA)-related sequences are known to have autosomal as well as heterogametic sex chromosomal copies, but specific regions of autosomal localization have not been described. We now demonstrate the presence of chromosome Y-related DNA sequences on proximal chromosome 17 in Sex-reversed (Sxr) and normal mice using in situ hybridization of mitotic chromosomes with 3H-labelled pCS316 (ref. 4), a probe that shows major hybridization to the proximal portion of the mouse chromosome Y. These data, and those of Washburn and Eicher, argue for a gene(s) related to sex determination or differentiation within the proximal portion of mouse chromosome 17.     

A high-resolution map of human chromosome 12

Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical maps for entire genomes.     

The DNA sequence of human chromosome 22

Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.     

An SNP map of human chromosome 22

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.