SPECIAL FEATURE target of 1 CM. One of the major efforts in this direction in the laboratory of Copeland and Jenkins (NCI, Frederick) resulted in reports of a current 800 loci mapped with an average resolution of 2 CM. Establishment of the genetic location of new markers is guaranteed on such a densely mapped cross. A second major effort (Seldin, Duke) has established 255 loci spanning 1200 CM of the mouse genome with an average spacing of 4.7 CM. A further genome-wide map has been constructed with an interspecific backcross carried out at the Pasteur Institute, Paris (Guenet). A European-based lOOO-animal interspecific backcross is underway with work carried out concurrently at two centers: the UK Medical Research Council Resource Centre, London, and the Institut Pasteur, Paris. At present, the anchor map is being laid down for this backcross. The European backcross will provide the resources for fine genetic mapping in individual chromosome regions as well as offer a facility to both mouse and human geneticists for localizing new probes. Microsatellite mapping: Simple sequence polymorphisms are having a major impact on genome-wide mapping. In addition to the use of classical probe technology for genetic mapping, mouse geneticists, like human geneticists, have turned to the use of microsatellites as a new tool for rapidly producing genetic maps. In mouse, the most common dinucleotide repeat, CA, is spaced, on average, every 18 kb. Although such markers are highly variant in interspecific crosses (>90%), they are also highly variant in intraspecific crosses so that for crosses involving different inbred strains, around half of the markers vary between the two parental strains. Two major efforts have been devoted to establishing genome-wide microsatellite maps. Bill Dietrich (Whitehead) reported the analysis of 310 microsatellite markers through a C57BL/6 X Mus castaneus cross (Friedman, Rockefeller); 98% of the markers are linked, providing an average marker spacing of 6 CM. John Todd (Oxford) has also localized over 100 microsatellites in the mouse genome. In addition to microsatellites, a new class of markersRAPDs (random amplified polymorphic DNAs)-generated by PCR with short random IO-nucleotide oligomers has been shown to be highly variable not only between species but also between laboratory strains (Elliott, Buffalo; Montagutelli, Paris; Sudweeks and Woodward, Utah) and represents an additional large source of markers for genome mapping. Integration of genetic mapping efforts: Reference loci. The full value of the detailed probe and microsatellite maps under construction will be realized only if the maps are crossreferenced. Chromosome committees (see below) have already determined for each chromosome a number of reference loci (spaced at intervals of lo-20 CM) that are to act as common anchor points for the various backcross mapping programs. It is a common aim that each cross should incorporate such reference loci that, in general, represent conserved genie loci that have already been characterized in a number of crosses. In addition, the cross-referencing of the various genetic mapping efforts in the mouse will enable the better use of the raw data within the newly developed database software for compilation of mouse genetic maps (see below).
MEETING REPORT
The Mouse Genome Project and Human Genetics A Report from the 5th International Mouse Genome Mapping Workshop, Lunteren, Holland STEPHEN
D. M. BROWN
Department of Biochemistry and Molecular Genetics, St. Mary’s Hospital Medical School, London W2 lPG, United Kingdom The mapping of the mouse genome is an integral part of the Human Genome Project. Decades of genetic mapping in the mouse allied with more recent advances in molecular mapping have provided a dense genetic map of the mouse genome. With a concomitant expansion in the human genetic map, it has been possible to characterize the bulk of conserved linkage groups between the mouse and the human genomes. This has given human geneticists unparalleled opportunity to search for mouse mutants that may be homologous to human disease genes, to identify candidate genes in the mouse that may be homologous to human disease genes, or to relate the mapping of candidate gene sequences in humans to mutant loci in the mouse. Where a homologous locus or mutation has been identified in the mouse, it provides an excellent vehicle for further studies of the genetics, pathophysiology, and potential therapy of human diseases with a genetic component. New mutations at mouse loci can be generated by a variety of techniques-radiation and chemical mutagenesis or gene targeting. The presence of deletion mutations is not only an aid to understanding the structure-function relationships at a particular locus but also an aid to mapping in the region. Furthermore, the development of rapid genetic mapping techniques in the mouse provides an efficient alternative route to human geneticists to determine map location of conserved sequences. The growing emphasis on the mouse as an important tool for the characterization and mapping of disease genes was underlined strongly at the recent 5th Mouse Genome Mapping Workshop held at Lunteren, Holland in October 1991. The Genetic
Map
Genome-wide mapping efforts are approaching a 1 -CM map of the mouse genome. The development of interspecific backcrosses as a genetic mapping tool in the mouse was an important turning point in the rapid development of a molecular map of the mouse genome. The divergence of the parental strains in interspecific backcrosses allows the mapping of every DNA marker; the crosses are multipoint and gene order is determined by a simple haplotype analysis. The fruits of this now standard technology were presented at this meeting: a number of genome-wide genetic maps have been developed at a number of centers using largely classical probe technology, and the density of mapped probes is rapidly approaching a
GENOMICS
13,
490-492
(1992)
490 All
Copyright ID 1992 rights of reproduction
0888-7543/92 $5.00 by Academic Press. Inc. in any form reserved.
SPECIAL FEATURE Genome-wide mapping efforts, in particular with the use of microsatellites, are aiding the localization of disease loci in the mouse genome. The powerful uses of dense genetic maps of the mouse genome have been most acutely demonstrated recently by the localization of a number of new loci involved with disease; in particular, these developments have been accelerated by the use of the genome-wide maps of rapidly usable, microsatellite loci. John Todd (Oxford) described the location of a number of loci involved with insulin-dependent (Type I) diabetes. A susceptibility gene had already been identified at the H-2 region on mouse Chromosome 17. Analysis of backcross progeny from a cross using the NOD (nonobese diabetic) strain of mouse with microsatellite loci covering most of the mouse genome has identified new susceptibility loci on mouse Chromosomes 1, 3, and 11 and defined the likely location of homologous loci in the human genome. Interestingly, the susceptibility gene on mouse Chromosome 1 is linked to the Lsh locus, which is involved with susceptibility to bacterial and parasitic infections and, like Type I diabetes, could have a macrophage involvement. Eric Lander (Whitehead) reported the use of his microsatellite map to locate the Min gene involved with multiple intestinal neoplasia to Chromosome 18. Furthermore, a major modifying locus on Chromosome 4 has been identified. Microsatellite analysis has also been used to analyze the segregation of loci involved with hypertension in a cross between the strokeprone spontaneously hypertensive rat and the normotensive WKY strain. A new library of microsatellites from the rat genome has been used to locate a major blood pressure gene (BPl) to Chromosome 10. Intriguingly, the BP1 gene is closely linked to the angiotensin-converting enzyme (ACE) gene. Microsatellite analysis of recombinant congenic strains segregating susceptibility to colon cancer has indicated the presence of two predisposing genes, Ssc-1 and Ssc-2, on Chromosome 2 and Chromosome 7, respectively (Moens and Demant, Amsterdam). Neither of these genes is synonymous with oncogenes or tumor-suppressor genes previously implicated in colon tumorigenesis. The Physical
Map
Some regions of the mouse genome have a very high marker to gedensity aiding physical mapping efforts. In addition nome-wide mapping efforts, there have been several major efforts, also employing interspecific backcrosses, to provide very detailed genetic maps in a number of defined regions of the mouse genome, in particular those harboring interesting mutations. In many cases, the backcross has included the mutation of interest to identify closely linked start points for the physical mapping and characterization of the mutant gene. In many cases, these detailed regional maps have a marker density of 1 CM or less (corresponding to 2 Mb or less) and allow the linkup of adjacent markers using pulsed-field gel electrophoresis to provide physical maps encompassing substantial megabase regions of the mouse genome. Three major regions of the central span of the mouse X chromosome have been physically linked-a 3-Mb region extending from the Gabra.3 to Cf-8 loci (Faust and Herman, Houston); a 1.5-Mb region distal to the T16H breakpoint and in the vicinity of the Zfx
locus (Hamvas and Brown, London); and a l-Mb region surrounding the Xist locus (Brockdorff and Rastan, London; Simmler and Avner, Paris). Other regions that have beenphysically mapped include major portions of the t-complex region of mouse Chromosome 17 (Silver, Princeton; Little, London); major portions of the albino deletion complex including a 4.5Mb region surrounding the alf/hsdr-1 locus (Kelsey, Heidelberg; Rinchik, Oak Ridge); a l-Mb region covering the diluteshort ear region of mouse Chromosome 9 (Kingsley, Stanford); and a large region surrounding the gld mutation on Chromosome 1 (Seldin, Duke). Each of these physical maps provides a framework for the establishment of overlying maps of YAC contigs, which will supply access to all of the underlying sequences. Whereas genome-wide approaches to YAC contig mapping probably have some way to go before fruition, the first major mapping efforts toward the establishment of YAC contigs in the mouse are likely to be in regions already saturated with markers and where rudimentary physical maps are in place. Access A number of mouse YAC libraries are now available. to mouse YAC libraries is a key issue for the development of not only the mouse genome program but that of human as well-the need to isolate mouse YAC clones homologous to human disease genes is an important step in beginning the genetic and, possibly, transgenic analysis in the mouse. Three YAC libraries have been constructed in the mouse-all are partial EcoRI libraries constructed with the pYAC4 vector: 1. Princeton (Tilghman)-C57BL/GJ female; >2 genomic equivalents; average size, 250 kb. 2. ICRF (Lehrach)-C3H male; 3 genomic equivalents; average size, 700 kb. 3. St. Mary’s (Brown)-C57BL/lO female; 3 genomic equivalents; average size, 250 kb and constructed in a rad52 mutant strain of yeast. The ICRF reference library system expects to be distributing library filters from both the ICRF and St. Mary’s libraries shortly. Recombination-deficient yeast strains carrying the rad52 mutation have been shown to stabilize certain YAC inserts, particularly those carrying repetitive sequences. Francois Chartier (London) reported the construction of the mouse rad52 library and discussed the possibility that the rad52 mutation may lower chimerism rates if chimerism is a function principally of recombination rather than coligation (see Green et al., 1991, Genomics 11: 658). The investigation of the library-wide effects of rad mutations may be an important step in improving mammalian YAC libraries to facilitate genomewide contiging strategies that are confounded by the presence of high levels of chimeric YAC clones. YAC contigs are being constructed in some well-mapped regions of the mouse genome. Embryonic YAC contigs have been constructed in various regions of the mouse genome notably across l the t-complex tle, London).
491
on Chromosome
17 (Silver,
Princeton;
Lit-
SPECIAL FEATURE l in the vicinity of the Zfx locus on the X chromosome (Hamvas, London). l around the Hba-ps4 gene, which lies close to the fused (Fu) locus on Chromosome 17 (Rossi, Princeton). l in the vicinity of the Xist locus on the X chromosome (Simmler and Avner, Paris). l in the region of the brown (b) locus on Chromosome 4 (Jackson, Edinburgh). l in the region of the quaking (qk) gene and extending into the Tme region on Chromosome 17 (Cox, Barlow, and Lehrach, London).
of Mammalian Genome (1: Sl-534). Aside from individual committee reports, the issue also includes listings of mouse DNA clones and probes and a chapter devoted to comparative mapping information of mouse and human genomes. This substantial text, which is to be updated annually, uncovers a wealth of experimentation over the entire mouse genome and will be a required lab compendium for all mouse and human geneticists, as well as provide comparative insights with the maps of other species. It represents a welcome addition to the Genome Project literature. In addition, it is envisaged that the chromosome committees will become responsible for verifying and editing mapping information input to the Mouse Genome Database. Direct access for chromosome committees to the Mouse Genome Database and associated software tools will enhance the preparation of future reports.
The construction of YAC contigs will be measurably improved by rapid techniques to identify overlapping clones-Segre (Whitehead) reported the use of various simple dimer, trimer, and tetramer repeat probes for YAC fingerprinting. Finally, preliminary work reported at the meeting by Bill Strauss (Whitehead) demonstrated the feasibility of manufacturing transgenic mice carrying YAC clones via the ES cell route. Successful introduction of a YAC clone containing a full-length collagen gene into ES cells has been achieved, and, subsequently, chimeric mice carrying the modified ES cells have been created. The availability of YAC clones to disease genes and their manipulation through transgenic systems are important end points of the Genome Project.
International
Genome
Society
Finally, Lunteren was the venue for the inauguration of the International Mammalian Genome Society (IMGS) and the first meeting of an elected secretariat. IMGS will be responsible for organizing the annual mapping workshops through a central office (at the moment situated in Buffalo, NY). IMGS will help coordinate the activities of chromosome committees and advise on database developments. IMGS will also act to help foster relationships with HUGO through the HUGO Mouse Genome Committee.
Informatics The goal of establishing a unitary database of mouse mapping information is well underway. A major program of database development directed and implemented by The Jackson Laboratory has begun and was described by Janan Eppig. This project under the title Mouse Genome Informatics, is not only developing a fundamental Mouse Genome Database but also creating software tools for the analysis and display of mouse mapping information. At present, the Mouse Genome Database includes the Genomic Database of the Mouse (GBASE), Homology Database (HMDP), and the Mouse Cytogenetic Database (MCD). In addition, Geneview, a software package for a wide variety of map presentations, has been developed at Harwell (Peters). A Mouse Gene Mapping Consortium, including all the major centers working on genome-wide mapping in the mouse, has been proposed. This consortium would have a pivotal role in maintaining the Mouse Genome Database and integrating genome-wide map information. Version 1.0 of the database has been released and is available on disk from The Jackson Laboratory. Chromosome
Mammalian
Summary l Genome-wide mapping efforts are moving toward the establishment of a ~-CM genetic map of the entire mouse genome. l The bulk of linkage groups conserved between the mouse and the human genomes has been identified. l Microsatellite mapping has had a major impact on the development of genome-wide genetic maps and, in particular, on genome-wide searches for polygenic disease loci. l Some substantial regions of the mouse genome have a marker density of 1 CM or less and many of these regions are now physically mapped. l Embryonic YAC contigs have been established in some physically mapped regions. l A unitary, global mouse mapping database-the Mouse Genome Database-is under development along with associated software tools. l Chromosome committees are having a major impact on the establishment and verification of chromosome maps through the preparation of published annual reports.
Committees
At the 4th Mouse Genome Mapping Workshop, committees were established for each chromosome. The task of each chromosome committee was to prepare a full report including a chromosome map and locus list as well as assign reference loci for each chromosome (see above). The successful fruits of these labors are presented in a recently published special issue
492
ACKNOWLEDGMENTS I thank all the members and the IMGS Secretariat article.
of the HUGO for reviewing
Mouse and
Genome commenting
Committee on this
MEETING REPORT
The Mouse Genome Project and Human Genetics A Report from the 5th International Mouse Genome Mapping Workshop, Lunteren, Holland STEPHEN
D. M. BROWN
Department of Biochemistry and Molecular Genetics, St. Mary’s Hospital Medical School, London W2 lPG, United Kingdom The mapping of the mouse genome is an integral part of the Human Genome Project. Decades of genetic mapping in the mouse allied with more recent advances in molecular mapping have provided a dense genetic map of the mouse genome. With a concomitant expansion in the human genetic map, it has been possible to characterize the bulk of conserved linkage groups between the mouse and the human genomes. This has given human geneticists unparalleled opportunity to search for mouse mutants that may be homologous to human disease genes, to identify candidate genes in the mouse that may be homologous to human disease genes, or to relate the mapping of candidate gene sequences in humans to mutant loci in the mouse. Where a homologous locus or mutation has been identified in the mouse, it provides an excellent vehicle for further studies of the genetics, pathophysiology, and potential therapy of human diseases with a genetic component. New mutations at mouse loci can be generated by a variety of techniques-radiation and chemical mutagenesis or gene targeting. The presence of deletion mutations is not only an aid to understanding the structure-function relationships at a particular locus but also an aid to mapping in the region. Furthermore, the development of rapid genetic mapping techniques in the mouse provides an efficient alternative route to human geneticists to determine map location of conserved sequences. The growing emphasis on the mouse as an important tool for the characterization and mapping of disease genes was underlined strongly at the recent 5th Mouse Genome Mapping Workshop held at Lunteren, Holland in October 1991. The Genetic
Map
Genome-wide mapping efforts are approaching a 1 -CM map of the mouse genome. The development of interspecific backcrosses as a genetic mapping tool in the mouse was an important turning point in the rapid development of a molecular map of the mouse genome. The divergence of the parental strains in interspecific backcrosses allows the mapping of every DNA marker; the crosses are multipoint and gene order is determined by a simple haplotype analysis. The fruits of this now standard technology were presented at this meeting: a number of genome-wide genetic maps have been developed at a number of centers using largely classical probe technology, and the density of mapped probes is rapidly approaching a
GENOMICS
13,
490-492
(1992)
490 All
Copyright ID 1992 rights of reproduction
0888-7543/92 $5.00 by Academic Press. Inc. in any form reserved.
SPECIAL FEATURE Genome-wide mapping efforts, in particular with the use of microsatellites, are aiding the localization of disease loci in the mouse genome. The powerful uses of dense genetic maps of the mouse genome have been most acutely demonstrated recently by the localization of a number of new loci involved with disease; in particular, these developments have been accelerated by the use of the genome-wide maps of rapidly usable, microsatellite loci. John Todd (Oxford) described the location of a number of loci involved with insulin-dependent (Type I) diabetes. A susceptibility gene had already been identified at the H-2 region on mouse Chromosome 17. Analysis of backcross progeny from a cross using the NOD (nonobese diabetic) strain of mouse with microsatellite loci covering most of the mouse genome has identified new susceptibility loci on mouse Chromosomes 1, 3, and 11 and defined the likely location of homologous loci in the human genome. Interestingly, the susceptibility gene on mouse Chromosome 1 is linked to the Lsh locus, which is involved with susceptibility to bacterial and parasitic infections and, like Type I diabetes, could have a macrophage involvement. Eric Lander (Whitehead) reported the use of his microsatellite map to locate the Min gene involved with multiple intestinal neoplasia to Chromosome 18. Furthermore, a major modifying locus on Chromosome 4 has been identified. Microsatellite analysis has also been used to analyze the segregation of loci involved with hypertension in a cross between the strokeprone spontaneously hypertensive rat and the normotensive WKY strain. A new library of microsatellites from the rat genome has been used to locate a major blood pressure gene (BPl) to Chromosome 10. Intriguingly, the BP1 gene is closely linked to the angiotensin-converting enzyme (ACE) gene. Microsatellite analysis of recombinant congenic strains segregating susceptibility to colon cancer has indicated the presence of two predisposing genes, Ssc-1 and Ssc-2, on Chromosome 2 and Chromosome 7, respectively (Moens and Demant, Amsterdam). Neither of these genes is synonymous with oncogenes or tumor-suppressor genes previously implicated in colon tumorigenesis. The Physical
Map
Some regions of the mouse genome have a very high marker to gedensity aiding physical mapping efforts. In addition nome-wide mapping efforts, there have been several major efforts, also employing interspecific backcrosses, to provide very detailed genetic maps in a number of defined regions of the mouse genome, in particular those harboring interesting mutations. In many cases, the backcross has included the mutation of interest to identify closely linked start points for the physical mapping and characterization of the mutant gene. In many cases, these detailed regional maps have a marker density of 1 CM or less (corresponding to 2 Mb or less) and allow the linkup of adjacent markers using pulsed-field gel electrophoresis to provide physical maps encompassing substantial megabase regions of the mouse genome. Three major regions of the central span of the mouse X chromosome have been physically linked-a 3-Mb region extending from the Gabra.3 to Cf-8 loci (Faust and Herman, Houston); a 1.5-Mb region distal to the T16H breakpoint and in the vicinity of the Zfx
locus (Hamvas and Brown, London); and a l-Mb region surrounding the Xist locus (Brockdorff and Rastan, London; Simmler and Avner, Paris). Other regions that have beenphysically mapped include major portions of the t-complex region of mouse Chromosome 17 (Silver, Princeton; Little, London); major portions of the albino deletion complex including a 4.5Mb region surrounding the alf/hsdr-1 locus (Kelsey, Heidelberg; Rinchik, Oak Ridge); a l-Mb region covering the diluteshort ear region of mouse Chromosome 9 (Kingsley, Stanford); and a large region surrounding the gld mutation on Chromosome 1 (Seldin, Duke). Each of these physical maps provides a framework for the establishment of overlying maps of YAC contigs, which will supply access to all of the underlying sequences. Whereas genome-wide approaches to YAC contig mapping probably have some way to go before fruition, the first major mapping efforts toward the establishment of YAC contigs in the mouse are likely to be in regions already saturated with markers and where rudimentary physical maps are in place. Access A number of mouse YAC libraries are now available. to mouse YAC libraries is a key issue for the development of not only the mouse genome program but that of human as well-the need to isolate mouse YAC clones homologous to human disease genes is an important step in beginning the genetic and, possibly, transgenic analysis in the mouse. Three YAC libraries have been constructed in the mouse-all are partial EcoRI libraries constructed with the pYAC4 vector: 1. Princeton (Tilghman)-C57BL/GJ female; >2 genomic equivalents; average size, 250 kb. 2. ICRF (Lehrach)-C3H male; 3 genomic equivalents; average size, 700 kb. 3. St. Mary’s (Brown)-C57BL/lO female; 3 genomic equivalents; average size, 250 kb and constructed in a rad52 mutant strain of yeast. The ICRF reference library system expects to be distributing library filters from both the ICRF and St. Mary’s libraries shortly. Recombination-deficient yeast strains carrying the rad52 mutation have been shown to stabilize certain YAC inserts, particularly those carrying repetitive sequences. Francois Chartier (London) reported the construction of the mouse rad52 library and discussed the possibility that the rad52 mutation may lower chimerism rates if chimerism is a function principally of recombination rather than coligation (see Green et al., 1991, Genomics 11: 658). The investigation of the library-wide effects of rad mutations may be an important step in improving mammalian YAC libraries to facilitate genomewide contiging strategies that are confounded by the presence of high levels of chimeric YAC clones. YAC contigs are being constructed in some well-mapped regions of the mouse genome. Embryonic YAC contigs have been constructed in various regions of the mouse genome notably across l the t-complex tle, London).
491
on Chromosome
17 (Silver,
Princeton;
Lit-
SPECIAL FEATURE l in the vicinity of the Zfx locus on the X chromosome (Hamvas, London). l around the Hba-ps4 gene, which lies close to the fused (Fu) locus on Chromosome 17 (Rossi, Princeton). l in the vicinity of the Xist locus on the X chromosome (Simmler and Avner, Paris). l in the region of the brown (b) locus on Chromosome 4 (Jackson, Edinburgh). l in the region of the quaking (qk) gene and extending into the Tme region on Chromosome 17 (Cox, Barlow, and Lehrach, London).
of Mammalian Genome (1: Sl-534). Aside from individual committee reports, the issue also includes listings of mouse DNA clones and probes and a chapter devoted to comparative mapping information of mouse and human genomes. This substantial text, which is to be updated annually, uncovers a wealth of experimentation over the entire mouse genome and will be a required lab compendium for all mouse and human geneticists, as well as provide comparative insights with the maps of other species. It represents a welcome addition to the Genome Project literature. In addition, it is envisaged that the chromosome committees will become responsible for verifying and editing mapping information input to the Mouse Genome Database. Direct access for chromosome committees to the Mouse Genome Database and associated software tools will enhance the preparation of future reports.
The construction of YAC contigs will be measurably improved by rapid techniques to identify overlapping clones-Segre (Whitehead) reported the use of various simple dimer, trimer, and tetramer repeat probes for YAC fingerprinting. Finally, preliminary work reported at the meeting by Bill Strauss (Whitehead) demonstrated the feasibility of manufacturing transgenic mice carrying YAC clones via the ES cell route. Successful introduction of a YAC clone containing a full-length collagen gene into ES cells has been achieved, and, subsequently, chimeric mice carrying the modified ES cells have been created. The availability of YAC clones to disease genes and their manipulation through transgenic systems are important end points of the Genome Project.
International
Genome
Society
Finally, Lunteren was the venue for the inauguration of the International Mammalian Genome Society (IMGS) and the first meeting of an elected secretariat. IMGS will be responsible for organizing the annual mapping workshops through a central office (at the moment situated in Buffalo, NY). IMGS will help coordinate the activities of chromosome committees and advise on database developments. IMGS will also act to help foster relationships with HUGO through the HUGO Mouse Genome Committee.
Informatics The goal of establishing a unitary database of mouse mapping information is well underway. A major program of database development directed and implemented by The Jackson Laboratory has begun and was described by Janan Eppig. This project under the title Mouse Genome Informatics, is not only developing a fundamental Mouse Genome Database but also creating software tools for the analysis and display of mouse mapping information. At present, the Mouse Genome Database includes the Genomic Database of the Mouse (GBASE), Homology Database (HMDP), and the Mouse Cytogenetic Database (MCD). In addition, Geneview, a software package for a wide variety of map presentations, has been developed at Harwell (Peters). A Mouse Gene Mapping Consortium, including all the major centers working on genome-wide mapping in the mouse, has been proposed. This consortium would have a pivotal role in maintaining the Mouse Genome Database and integrating genome-wide map information. Version 1.0 of the database has been released and is available on disk from The Jackson Laboratory. Chromosome
Mammalian
Summary l Genome-wide mapping efforts are moving toward the establishment of a ~-CM genetic map of the entire mouse genome. l The bulk of linkage groups conserved between the mouse and the human genomes has been identified. l Microsatellite mapping has had a major impact on the development of genome-wide genetic maps and, in particular, on genome-wide searches for polygenic disease loci. l Some substantial regions of the mouse genome have a marker density of 1 CM or less and many of these regions are now physically mapped. l Embryonic YAC contigs have been established in some physically mapped regions. l A unitary, global mouse mapping database-the Mouse Genome Database-is under development along with associated software tools. l Chromosome committees are having a major impact on the establishment and verification of chromosome maps through the preparation of published annual reports.
Committees
At the 4th Mouse Genome Mapping Workshop, committees were established for each chromosome. The task of each chromosome committee was to prepare a full report including a chromosome map and locus list as well as assign reference loci for each chromosome (see above). The successful fruits of these labors are presented in a recently published special issue
492
ACKNOWLEDGMENTS I thank all the members and the IMGS Secretariat article.
of the HUGO for reviewing
Mouse and
Genome commenting
Committee on this
