A Set of STS Assays Targeting the Chromosome 22 Physical Framework Markers

The widespread use of the sequence-tagged site (STS) as a quick, efficient, and reproducible assay for comparing physical and genetic map information promises to facilitate greatly long-range goals of time mapping of the human genome. We have designed 21 STS assays for loci on human chromosome 22. These assays primarily tag the physical framework markers of the long arm of 22, but additional assays have been designed from known genes and loci in the neurofibromatosis 2 (NF2) region. The availability of these assays will make these loci available to the research community without physical transfer of materials and will serve as start points for further efforts to physically map chromosome 22 with yeast artificial chromosome clones.     

Detailed comparative gene map of rat chromosome 1 with mouse and human genomes and physical mapping of an evolutionary chromosomal breakpoint

We report the localization of 92 new gene-based markers assigned to rat chromosome 1 by linkage or radiation hybrid mapping. The markers were chosen to enrich gene mapping data in a region of the rat chromosome known to contain several of the principal quantitative trait loci in rodent models of human multifactorial disease. The composite map reported here provides map information on a total of 139 known genes, including 80 that have been localized in mouse and 109 that have been localized in human, and integrates the gene-based markers with anonymous microsatellites. The evolutionary breakpoints identifying 16 segments that are homologous regions in the human genome are defined. These data will facilitate genetic and comparative mapping studies and identification of novel candidate genes for the quantitative trait loci that have been localized to the region.     

畜禽生产性状主效基因定位技术与方法研究进展

鉴定畜禽重要生产性状形成的关键遗传因子,揭示其产生的分子遗传机制,对动物新品种的培育及特色遗传资源的开发利用具有重要意义。高通量分析技术诞生前,标记数量性状位点(quantitative trait loci,QTL)连锁分析和候选基因分析法作为鉴定畜禽生产性状QTL和主效基因主要方法,但由于其技术局限性,性状因果基因鉴定的效率并不高。人类基因组计划(human genome project, HGP)开启了以大数据为特征的生命科学研究的序幕,在HGP完成后的20余年间,快速发展的高通量分析技术使人们研究生物学问题的思路和方法发生了巨大改变。本综述就近年来被广泛用于畜禽重要性状的候选基因定位的方法与技术进行了较全面的综述,以期为同行提供参考。     

Advances in the human genome project – A review

While celebrating its fifth official birthday last year it seems that the Human Genome Project (HGP) has and will continue to yield important biochemical information to mankind. It is exhilarating to think about the transition from studying genome structure to understanding genome function. The collective actions of information dessimination, technology development for efficient and faster sequencing, high-volume sequencing and developing model organisms has led to its success sofar. Various genome-wide STS-based human maps were completed in 1995, including a genetic map, a YAC map, a RH map with, and an integrated YAC-RH genetic map. These maps provide comprehensive frameworks for positioning additional loci, with the current genetic and RH maps spanning essentially 100% of the human genome and the YAC maps covering 95%. Few genes, however, have yet been localized on these framework maps. To date the Human Genome Project has experienced gratifying success. The technology and data produced by the genome project will provide a strong stimulus to broad areas of biological research and biotechnology. However, enormous challenges remain.     

Identification and Applications of Repetitive Probes for Gene Mapping in the Mouse

Interspecific mouse hybrids that are viable and fertile provide a wealth of genetic variation that is useful for gene mapping. We are using this genetic variation to develop multilocus linkage maps of the mouse genome. As an outgrowth of this work, we have identified three repetitive probes that collectively identify 28 loci dispersed on 16 of the 19 mouse autosomes and the X chromosome. These loci establish a skeleton linkage map that can be used to detect linkage over much of the mouse genome. The molecular probes are derived from the mouse mammary tumor virus envelope gene, the ornithine decarboxylase gene, and the triose phosphate isomerase gene. The ability to scan the mouse genome quickly and efficiently in an interspecific cross using these three repetitive probes makes this system a powerful tool for identifying the chromosomal location of mutations that have yet to be cloned, mapping multigenic traits, and identifying recessive protooncogene loci associated with murine neoplastic disease. Ultimately, interspecific hybrids in conjunction with repetitive and single-copy probes will provide a rapid means to access virtually any gene of interest in the mouse genome at the molecular level.     

The Genetics of a Small Autosomal Region of DROSOPHILA MELANOGASTER Containing the Structural Gene for Alcohol Dehydrogenase. II. Lethal Mutations in the Region

Forty-seven lethal mutations and alleles of nine visible loci (including alcohol dehydrogenase) have been mapped by both deficiency mapping and, in most cases, by recombination mapping to a small region (34D-35C) of chromosome arm 2L of Drosophila melanogaster. The lethals fall into approximately 21 complementation groups, and we estimate that the total number of lethal plus visible complementation groups within the 34-band deficiency, Df(2L)64j, is approximately 34, a remarkable numerical coincidence. The possible genetic significance of this coincidence is discussed. Lethals mapping close to the structural gene for alcohol dehydrogenase, both distally and proximally, have been identified and will be used for the construction of selective crosses for the study of exchange within this locus. Despite many abnormal cytological features (e.g., ectopic pairing, weak points) region 35 of chromosome arm 2L does not display any unusual genetic features; indeed, in terms of the amount of recombination per band and the average map distance between adjacent loci, this region is similar to that between zeste and white on the X chromosome.     

A maize map standard with sequenced core markers, grass genome reference points and 932 expressed sequence tagged sites (ESTs) in a 1736-locus map.

We have constructed a 1736-locus maize genome map containing1156 loci probed by cDNAs, 545 probed by random genomic clones, 16 by simple sequence repeats (SSRs), 14 by isozymes, and 5 by anonymous clones. Sequence information is available for 56% of the loci with 66% of the sequenced loci assigned functions. A total of 596 new ESTs were mapped from a B73 library of 5-wk-old shoots. The map contains 237 loci probed by barley, oat, wheat, rice, or tripsacum clones, which serve as grass genome reference points in comparisons between maize and other grass maps. Ninety core markers selected for low copy number, high polymorphism, and even spacing along the chromosome delineate the 100 bins on the map. The average bin size is 17 cM. Use of bin assignments enables comparison among different maize mapping populations and experiments including those involving cytogenetic stocks, mutants, or quantitative trait loci. Integration of nonmaize markers in the map extends the resources available for gene discovery beyond the boundaries of maize mapping information into the expanse of map, sequence, and phenotype information from other grass species. This map provides a foundation for numerous basic and applied investigations including studies of gene organization, gene and genome evolution, targeted cloning, and dissection of complex traits.     

70个水稻微卫星标记染色体位置的更正

微卫星标记(SSR)因其操作简单和稳定可靠的特点而成为一种重要的分子标记,被广泛应用于遗传作图和种质鉴定等方面。但其在染色体上位置的正确性将直接影响到基因定位的正确性和后续研究的方向。利用美国国家生物信息技术中心(NCBI)网站的Blast程序,将2740个SSR标记的前后引物序列与水稻粳稻品种日本晴基因组进行比对,共发现70个标记位于另一条染色体,对这70个标记重新锚定的染色体进行了更正。这将有助于今后水稻分子标记遗传连锁图的正确构建。     

A genetic linkage map and comparative genome analysis of common carp (Cyprinus carpio L.) using microsatellites and SNPs

A genetic linkage map is a powerful research tool for mapping traits of interest and is essential to understanding genome evolution. The aim of this study is to provide an expanded genetic linkage map of common carp to effectively carry out quantitative trait loci analysis and conduct comparative mapping analysis between lineages. Here, we constructed a genetic linkage map of common carp (Cyprinus carpio L.) using microsatellite and single-nucleotide polymorphism (SNP) markers in a 159 sibling family. A total of 246 microsatellites and 306 SNP polymorphic markers were genotyped in this family. Linkage analysis using JoinMap 4.0 organized 427 markers (186 microsatellites and 241 SNPs) to 50 linkage groups, ranging in size from 1.4 to 130.1 cM. Each group contained 2-30 markers. The linkage map covered a genetic distance of 2,039.2 cM and the average interval for markers within the linkage groups was approximately 6.4 cM. In addition, comparative genome analysis within five model teleost fish revealed a high percentage (74.7%) of conserved loci corresponding to zebrafish chromosomes. In most cases, each zebrafish chromosome comprised two common carp linkage groups. The comparative analysis also revealed independent chromosome rearrangements in common carp and zebrafish. The linkage map will be of great assistance in mapping genes of interest and serve as a reference to approach comparative mapping and enable further insights into the comprehensive investigations of genome evolution of common carp.     

A high-resolution radiation hybrid map of the proximal portion of mouse chromosome 5

Radiation hybrid (RH) mapping of the mouse genome provides a useful tool in the integration of existing genetic and physical maps, as well as in the ongoing effort to generate a dense map of expressed sequence tags. To facilitate functional analysis of mouse Chromosome 5, we have constructed a high-resolution RH map spanning 75 cM of the chromosome. During the course of these studies, we have developed RHBase, an RH data management program that provides data storage and an interface to several RH mapping programs and databases. We have typed 95 markers on the T31 RH panel and generated an integrated map, pooling data from several sources. The integrated RH map ranges from the most proximal marker, D5Mit331 (Chromosome Committee offset, 3 cM), to D5Mit326, 74.5 cM distal on our genetic map (Chromosome Committee offset, 80 cM), and consists of 138 markers, including 89 simple sequence length polymorphic markers, 11 sequence-tagged sites generated from BAC end sequence, and 38 gene loci, and represents average coverage of approximately one locus per 0.5 cM with some regions more densely mapped. In addition to the RH mapping of markers and genes previously localized on mouse Chromosome 5, this RH map places the alpha-4 GABA(A) receptor subunit gene (Gabra4) in the central portion of the chromosome, in the vicinity of the cluster of three other GABA(A) receptor subunit genes (Gabrg1-Gabra2-Gabrb1). Our mapping effort has also defined a new cluster of four genes in the semaphorin gene family (Sema3a, Sema3c, Sema3d, and Sema3e) and the Wolfram syndrome gene (Wfs1) in this region of the chromosome.     

An integrative approach for the identification of quantitative trait loci

The genetic dissection of complex traits is one of the most difficult and most important challenges facing science today. We discuss here an integrative approach to quantitative trait loci (QTL) mapping in mice. This approach makes use of the wealth of genetic tools available in mice, as well as the recent advances in genome sequence data already available for a number of inbred mouse strains. We have developed mapping strategies that allow a stepwise narrowing of a QTL mapping interval, prioritizing candidate genes for further analysis with the potential of identifying the most probable candidate gene for the given trait. This approach integrates traditional mapping tools, fine mapping tools, sequence-based analysis, bioinformatics and gene expression.     

Mapping the bovine genome: methodological aspects and strategy*

Summary
The mapping of genes that control traits of economic importance will ultimately lead to the unravelling of the molecular basis of genetic variation. The main prerequisite for mapping of the unknown genes is a sufficient number of highly polymorphic marker loci which are evenly distributed along the chromosomes. The establishment of such a marker map in cattle and other species is based on methods used in human gene mapping. Comparative mapping facilitates saturation of the chromosomes with markers by utilizing the high degree of conservation of synteny among mammalian species. Comparative mapping will also allow access to the detailed mapping data and to extensive sequence information expected from the human genome initiative.     

Genetic analysis and genome mapping in Raphanus.

The first genetic map of the Raphanus genome was developed based on meiosis in a hybrid between Raphanus sativus (cultivated radish) and Raphanus raphanistrum (wild radish). This hybrid was used to produce a BC1 population of 54 individuals and an F2 population of 85 individuals. A total of 236 marker loci were assayed in these populations using a set of 144 informative Brassica RFLP probes previously used for genetic mapping in other crucifer species. The genetic maps derived from the BC1 and F2 populations were perfectly collinear and were integrated to produce a robust Raphanus map. Cytological observations demonstrated strict bivalent pairing in the R. sativus x R. raphanistrum hybrids. Productive pairing along the length of each chromosome was confirmed by the identification of nine extensive linkage groups and the lack of clustering of marker loci. Indeed, the distributions of both marker loci and crossovers was more random than those reported for other crop species. The genetic markers and the reference map of Raphanus will be of considerable value for future trait mapping and marker-assisted breeding in this crop, as well as in the intergenomic transfer of Raphanus genes into Brassica crops. The future benefits of comparative mapping with Arabidopsis and Brassica species are also discussed.     

Advances in pig genomics and functional gene discovery

Advances in pig gene identification, mapping and functional analysis have continued to make rapid progress. The porcine genetic linkage map now has nearly 3000 loci, including several hundred genes, and is likely to expand considerably in the next few years, with many more genes and amplified fragment length polymorphism (AFLP) markers being added to the map. The physical genetic map is also growing rapidly and has over 3000 genes and markers. Several recent quantitative trait loci (QTL) scans and candidate gene analyses have identified important chromosomal regions and individual genes associated with traits of economic interest. The commercial pig industry is actively using this information and traditional performance information to improve pig production by marker-assisted selection (MAS). Research to study the co-expression of thousands of genes is now advancing and methods to combine these approaches to aid in gene discovery are under way. The pig's role in xenotransplantation and biomedical research makes the study of its genome important for the study of human disease. This review will briefly describe advances made, directions for future research and the implications for both the pig industry and human health.     

A comparative map of wild rice (Zizania palustris L. 2n=2x=30)

We present the first genetic map of wild rice (Zizania palustris L., 2n=2x=30), a native aquatic grain of northern North America. This map is composed principally of previously mapped RFLP (restriction fragment length polymorphism) genetic markers from rice (Oryza sativa 2n=2x=24). The map is important as a foundation for genetic and crop improvement studies as well as a reference for genome organization comparisons among species of Gramineae. A comparative mapping approach with rice is especially useful because wild rice is grouped in the same subfamily, Oryzoideae, and no other mapping comparison has yet been made within the subfamily. As rice is the reference point for mapping and gene cloning in cereals, establishing a consensus map within the subfamily identifies conserved and unique regions. The genomes of wild rice and rice differ in total DNA content (wild rice has twice that of rice) and the number of chromosome pairs (wild rice=15 versus rice=12). The wild rice linkage map reported herein consists of 121 RFLP markers on 16 linkage groups spanning 1805 cM. Two linkage groups consist of only two markers. Colinear markers were found representing all rice linkage groups except #12. The majority of rice loci mapped to colinearly arranged arrays in wild rice (92 of 118). Features of the map include duplication of portions of three rice linkage groups and three possible translocations. The map gives basic information on the composition of the wild rice genome and provides tools to assist in the domestication of this important food source. Received: 25 August 1998 / Accepted: 20 February 1999     

Genomics and self-knowledge: implications for societal research and debate

Abstract

When the Human Genome Project (HGP) was launched, our genome was presented as our ‘blueprint’, a metaphor reflecting a genetic deterministic epistemology. Eventually, however, the HGP undermined rather than strengthened the understanding of genomes as blueprints and of genes as ultimate causal units. A symbolical turning point was the discovery that the human genome only contains～22,500 genes. Initially, this was seen as a narcissistic offence. Gradually, however, it strengthened the shift from traditional genetics and biotechnology (i.e., gene-oriented approaches) to genomics, i.e. genome-oriented or systems approaches, emphasizing complexity. The 20th century can be regarded as the century of biotechnology and of the gene. Its history demonstrated that the will to know (notably: to know ourselves) has never been a disinterested affair: it is driven by a will to improve (notably: to improve ourselves). In this article it is claimed that, as genomics takes us beyond a genetic deterministic understanding of life, this must have consequences for societal research and debate as well. Policies for self-improvement will increasingly rely on the use of complex interpretation. Therefore, the emphasis must shift from issues such as genetic manipulation and human enhancement to issues involved in governance of novel forms of information.     

A primary genetic map of markers of human chromosome 10

We have constructed a primary genetic map for human chromosome 10 from 13 polymorphic marker systems defining 11 loci, using a new gene mapping algorithm implemented in the computer program GMS. The loci form a continuous genetic map that spans approximately 116 cM in males and 170 cM in females. These loci provide regularly spaced anchor points for linkage studies, except for one interval that is 28 cM in males and 64 cM in females.     

The PiGMaP consortium linkage map of the pig (Sus scrofa)

A linkage map of the porcine genome has been developed by segregation analysis of 239 genetic markers. Eighty-one of these markers correspond to known genes. Linkage groups have been assigned to all 18 autosomes plus the X Chromosome (Chr). As 69 of the markers on the linkage map have also been mapped physically (by others), there is significant integration of linkage and physical map data. Six informative markers failed to show linkage to these maps. As in other species, the genetic map of the heterogametic sex (male) was significantly shorter (16.5 Morgans) than the genetic map of the homogametic sex (female) (21.5 Morgans). The sex-averaged genetic map of the pig was estimated to be 18 Morgans in length. Mapping information for 61 Type I loci (genes) enhances the contribution of the pig gene map to comparative gene mapping. Because the linkage map incorporates both highly polymorphic Type II loci, predominantly microsatellites, and Type I loci, it will be useful both for large experiments to map quantitative trait loci and for the subsequent isolation of trait genes following a comparative and candidate gene approach.     

A gene map of the rat derived from linkage analysis and related regions in the mouse and human genomes

We report the localization by linkage analysis in the rat genome of 148 new markers derived from 128 distinct known gene sequences, ESTs, and anonymous sequences selected in GenBank database on the basis of the presence of a repeated element. The composite linkage map of the rat contributed by our group integrates mapping information on a total of 370 different known genes, ESTs, and anonymous mouse or human sequences, and provides a valuable tool for comparative genome analysis. 206 and 254 homologous loci were identified in the mouse and human genomes respectively. Our linkage map, which combines both anonymous markers and gene markers, should facilitate the advancement of genetic studies for a wide variety of rat models characterized for complete phenotypes. The comparative genome mapping should define genetic regions in human likely to be homologous to susceptibility loci identified in rat and provide useful information for the identification of new potential candidates for genetic disorders. Received: 2 January 1999 / Accepted: 7 March 1999