* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download The Chicken Gene Map
Behavioural genetics wikipedia , lookup
Genetic testing wikipedia , lookup
Neocentromere wikipedia , lookup
X-inactivation wikipedia , lookup
Transposable element wikipedia , lookup
Gene expression programming wikipedia , lookup
Medical genetics wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
Population genetics wikipedia , lookup
Non-coding DNA wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Microsatellite wikipedia , lookup
Pathogenomics wikipedia , lookup
Human genetic variation wikipedia , lookup
Minimal genome wikipedia , lookup
Whole genome sequencing wikipedia , lookup
Genetic engineering wikipedia , lookup
Designer baby wikipedia , lookup
Human genome wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
History of genetic engineering wikipedia , lookup
Genomic library wikipedia , lookup
Microevolution wikipedia , lookup
Public health genomics wikipedia , lookup
Genome editing wikipedia , lookup
Human Genome Project wikipedia , lookup
Quantitative trait locus wikipedia , lookup
The Chicken Gene Map David W. Burt and Hans H. Cheng INTRODUCTION Most efforts to map the genomes of birds have concentrated almost exclusively on the domesticated chicken (Gallus gallus) and on very few other species. Two reasons for this bias are the importance of chicken as a major source of meat and egg products and as a model of vertebrate development. The first genetic linkage map of the chicken was published in 1936 by Hutt (1936) and represented the first map reported for any domestic farm animal species. Updates of this classical map have been published periodically, with the most recent being that of Bitgood and Somes (1993). The small size of the chicken genome (1.2 billion base-pairs; Bloom and others 1993) and the ability to isolate DNA from nucleated red blood cells (note: red blood cells in mammals lack nuclei) make it well suited for gene mapping. Despite these advantages, 6 decades of genetic linkage mapping have produced a limited map. International collaborative efforts to produce a molecular map of the chicken genome have been established only in the last 5 yr (Burt and others 1995,1997). REASONS FOR MAPPING THIS SPECIES The chicken genome is being mapped to discover genetic markers of traits of economic value (such as meat and egg production), to discover animal models for quantitative traits, genetic disease, and developmental defects, and to aid studies on the evolution of the vertebrate genome (such as chromosome evolution and speciation). Most economically important traits in poultry, such as weight, fatness, and disease resistance, are controlled by many genes located at quantitative trait loci (QTLs1). The study of such traits requires crosses between lines that show extreme differences in phenotypes and large pedigrees (such as 500 or more progeny of an F 2 intercross). These types of studies are extremely difficult in David W. Burt, Ph.D., is Principal Investigator in the Division of Molecular Biology, Roslin Institute of Edinburgh, Midlothian, United Kingdom. Hans H. Cheng, Ph.D., is Principal Investigator in the Avian Disease and Oncology Laboratory of the US Department of Agriculture Agricultural Research Center, East Lansing, Michigan. 'Abbreviations used in this paper: ADW, autosomal dwarfism; BAC, bacterial artificial chromosome; FISH, fluorescence in situ hybridization; HMG1C, high mobility group protein I-C; QTL, quantitative trait locus; WL, White Leghorn; WWW, World Wide Web; YAC, yeast artificial chromosome. Volume 39, Numbers 2 and 3 1998 humans. However, many QTL mapping projects are under way in poultry (Burt and others 1997), and when linkage is established, candidate genes may be identified. Like any other chromosomal region, QTLs and the genes encoded within them are likely to be conserved across species. So, for example, QTLs for growth and fatness in poultry are likely to control similar phenotypes in humans and other vertebrates. Currently, more than 300 mutants have been described in the chicken (Crawford 1990), and more than 80 have been mapped. The localization and characterization of these QTLs will increase our understanding of the basic mechanisms of development, physiology, and oncogenesis, as well as identify new animal models of human disease. A particular advantage of data on the chicken genome is the evolutionary depth of comparisons between birds and mammals, groups that diverged 350 million yr ago (Andersson and others 1996). Sufficient data have now accumulated on the gene maps (see section below, Comparative Gene Maps) to enable comparison of the arrangements of genes on human and chicken genomes. In the past, one could only speculate on map homologies based on morphological characteristics. Information from recent maps of the chicken genome has led to the surprising conclusion that there is considerable similarity to the human genome (Andersson and others 1996; Burt and others 1995, 1997). CURRENT MAP STATUS, APPROACHES USED TO GENERATE THE MAP, AND ANTICIPATED FUTURE CONTRIBUTIONS OF THE MAP International Reference Families International collaborations to map the chicken genome have been based mostly on 2 reference mapping populations, 1 in the United States (East Lansing, Michigan) and the other in the United Kingdom (Compton). To generate the East Lansing mapping family, a single male from the inbred UCD001 Jungle Fowl line was mated to a single female from the inbred UCD-003 White Leghorn (WL1) line to produce F, progeny (Crittenden and others 1993). Two ¥{ males were individually backcrossed to 10 and 8 UCD-003 WL females to produce 208 and 192 progeny, respectively. Large quantities of blood and DNA from each animal were stored away in aliquots. A subset of 52 progeny (1 F t male x 4 WL females) forms the basic East Lansing mapping panel. 229 To generate the Compton mapping family, a single line 151 male was mated to a single line N female to produce progeny (Bumstead and Palyga 1992). Unlike the East Lansing mapping family, a single F, female individual was backcrossed to a line 151 male to generate the mapping family. The consequence of using an Fj female instead of a male in the backcross is that the Z chromosome cannot be mapped in the Compton mapping family; however, the pseudoautosomal region of the W chromosome can be mapped. DNA from a panel of 56 individuals forms the primary mapping panel. Recently, a third chicken reference family was produced in Wageningen, The Netherlands, by a collaborative effort between Martien Groenen and Euribrid, a European poultry breeding company. Using 2 commercial broiler lines, 10 F2 families containing a total of 456 progeny were produced (Crooijmans and others 1996; M. A. M. Groenen, Wageningen University, personal communication, 1998). The DNA of this mapping family is not yet publicly available. Genetic Markers TABLE 1 Laboratories associated with the Chicken Genome Project Laboratory Director Institution Bernard Benkel Centre for Food & Animal Research, Ottawa, Ontario, Canada INRA Centre de Recherche de Jouy-en-Josas, France Institute for Animal Health, Compton, UK University of Leicester, Leicester, UK Roslin Institute (Edinburgh), Midlothian, Scotland, UK Avian Disease & Oncology Laboratory, East Lansing, Ml, USA Michigan State University, East Lansing, Ml, USA Michigan State University, East Lansing, Ml, USA Technical University of Munich, Freising, Germany Wageningen Agricultural University, The Netherlands The Hebrew University of Jerusalem, Rehovot, Israel Iowa State University, Ames, IA, USA University of Minnesota, St. Paul, MN,USA Beckman Research Institute of the City of Hope, Duarte, CA, USA Avian Disease & Oncology Laboratory, East Lansing, Ml, USA The Hebrew University of Jerusalem, Jerusalem, Israel National Institute of Agrobiological Resources, Ibaraki, Japan INRA Centre de Recherche de Toulouse, Castenet Tolosan, France Michele Tixier-Boicharda Nat Bumsteada Terry Burkea Dave Burta Hans Cheng Lyman Crittenden Jerry Dodgson Ruedi Friesa Genetic markers comprise the other major component required to build a genetic map. Since map development is additive when multiple laboratories genotype markers on a common mapping family, an early decision was made to distribute the DNAs from the internationally recognized mapping families (East Lansing and Compton) to interested groups. In Table 1, the major laboratories associated with the Chicken Genome Project are listed. Each group genotypes their markers on the reference family and sends the data to the map curator (Hans Cheng for East Lansing and Nat Bumstead for Compton) for marker placement. The information is then made publicly available through the chicken genome database, Arkdb-CHICK (D. W. Burt, http://www.ri.bbsrc.ac.uk/). The reference mapping populations have been typed using markers for expressed genes (that is, cloned genes and anonymous cDNAs) and anonymous markers (random genomic clones, endogenous retroviruses, short interspersed repeats [SINEs], or chicken repeat 1 [CR1] repeats, random amplified polymorphic DNAs [RAPDs], minisatellites or variable number tandem repeats [VNTRs], and microsatellites). Approximately 1200 marker genes have been mapped on the East Lansing and Compton maps (Table 2). Genetic Linkage Maps The status of each genetic map is continually changing, but at the time of this writing (October 1998), the status is as follows (Table 3). On the East Lansing map, 98% of loci are linked to at least 1 other locus containing 830 loci in 39 linkage groups, for a total length of 4061 cM with an average marker spacing of 5 cM. On the Compton map, 96% of loci are linked to at least 1 other locus containing 420 loci in 36 linkage groups, and the total length is 4262 cM with an aver230 Martien Groenena Jossi Hillel Susan Lamont Abel Ponce de Leon Marcia Miller Eugene Smith Morris Soller Hideaki Takahashi Alain Vignala 'Members of the European CHICKMAP group. age marker spacing of 10 cM. On the Wageningen map, 98% loci are linked to at least 1 other locus containing 471 microsatellite loci in 28 linkage groups, and the total length is 3682 cM with an average marker spacing of 8 cM. The total genetic length of each map was estimated (D. W. Burt unpublished) from a summation of the genetic distance between loci (recombination fractions were converted to genetic distance using the method of Kosambi 1944) and using an end correction to adjust for failure to sample telomeric regions (Morton 1991). Cytological data suggest that the total genetic length of the chicken genome is 2800 to 3300 cM (Bitgood and Shoffner 1990; Rodionov and others 1992). ILAR Journal TABLE 2 Genetic markers on the chicken mapa Marker type Total SINES'3 or CR1fa repeats Endogenous retroviruses VNTRsb or minisatellites Random genomic clones RAPDsb Classical genes cDNAs of unknown function cDNAs of known function Microsatellites associated with genes Total number of genes Anonymous microsatellites Total number of microsatellites Total number of markers 45 37 52 109 68 10 37 92 43 182 634 677 1127 netic maps of the 2 sexes can be compared in the Wageningen map; and as in other species, the genetic map of the heterogametic sex (female in birds) is shorter than the genetic map of the homogametic sex (male in birds), but only by 1% (M. A. M. Groenen, Wageningen University, personal communication, 1998). A second major goal is to isolate and map sufficient microsatellite markers to cover the entire genome for whole genome mapping studies. So far, 677 microsatellites have been mapped, at an average spacing of 9 cM and with a range of 6 to 20 cM (Cheng and Crittenden 1994; Cheng and others 1995; Crooijmans and others 1996, 1997; Gibbs and others 1997). Physical Maps and Resources a Data from Arkdb-CHICK, October 1998. b CR1, chicken repeat 1; RAPD, random amplified polymorphic DNA; SINES, short interspersed elements; VNTR, variable number of tandem repeats. Thus, the current genetic maps are almost complete, although there is still some uncertainty due to problems associated with microchromosomes. One goal is to assign sufficient common markers to enable cross-comparison between maps. Significant progress has already been made with 28 consensus linkage groups defined from an expected total of 39, with 46 linkage groups in total (Table 4). However, many small linkage groups remain to be associated—7 on the Compton map and 12 on the East Lansing map. The order of markers on all maps is in general agreement, although the Compton map is larger than either the East Lansing map or the Wageningen map. Ge- Physical maps show the location of markers on individual chromosomes and provide landmarks for the assignment and orientation of linkage groups to specific chromosomes. Integration of the physical and genetic maps helps to support marker order, resolve discrepancies, and determine the coverage of maps. Chicken chromosomes are very numerous (2n=78) and are classified into macrochromosomes or microchromosomes based on their size. The larger macrochromosomes are easy to differentiate based on their morphology; however, the microchromosomes are too small to be recognized individually using current banding techniques. The Z and W chromosomes are the sex chromosomes. A standard G-banded karyotype was developed by a committee consisting of J. Bitgood (United States), K. Ladjadi (France), F. A. Ponce de Leon (United States), and M. Tixier-Boichard (France) as an aid for comparing physical maps of the macrochromosomes (Ponce de Leon and others 1993). Some linkage groups have been assigned to specific chromosomes by TABLE 3 Size of genetic linkage groups on the international reference maps East Lansing, M l , size (cM) Linkage group No. of markers 1 2 3 4 5 6 7 8 Z 155 103 76 57 47 31 26 26 57 522 497 338 218 211 122 146 103 222 12.9 12.2 8.3 5.4 5.2 3.0 3.6 2.5 5.5 252 830 1682 4061 41.4 100.0 (%a) w MIC C Total Exp % male genome b 20.5 14.7 11.2 8.8 5.2 3.4 3.3 2.4 8.2 0.0 22.3 100.0 No. of markers Compton, UK, size (cM) (%a) 69 58 51 38 26 9 20 5 738 462 331 433 171 120 149 162 17.3 10.8 7.8 10.2 4.0 2.8 3.5 3.8 12 132 420 95 1601 4262 2.2 37.6 100.0 Exp % female genomefa 20.8 15.1 11.5 9.1 5.3 3.5 3.4 2.5 4.2 1.4 23.2 100.0 ••Percentage of the total genome. b Expected percentage of DNA content based on direct measures of fluorescence (Smith and Burt 1998) (data from Arkdb-CHICK, October 1998). C MIC, microchromosomes. Volume 39, Numbers 2 and 3 1998 231 TABLE 4 Comparison of East Lansing, Ml, and Compton, UK, genetic linkage groups Linkage group East Lansing size (cM) Z 222 w 1 2 3 4 5 6 7 8 16 C21 C22 C24 C26 C30 C32 C34 E04 El 7 E24 E32 E38 E41 a 522 497 338 218 211 122 146 103 48 21 8 0 4 35 74 Compton size (cM) 95 738 462 331 433 171 120 149 162 80 31 0 0 4 84 11 11 0 Chr. type Linkage group East Lansing size (cM) MAC a MIC MAC MAC MAC MAC MAC MAC MAC MAC MIC MIC? MIC? MIC? MIC? MIC? MIC? MIC? MIC? MIC? MIC? MIC MICa? MIC E47 E52 E54 E56 E57 E58 E16C17 E18C15 E22C19 E25C31 E26C13 E27C36 E29C09 E30C14 E31C25 E35C18 E36C06 E40C29 E46C08 E48C28 E49C20 E50C23 E53C34 E59C35 14 54 107 8 14 24 52 38 88 45 62 50 85 63 117 39 117 35 83 90 90 39 105 47 Compton size (cM) 68 50 81 42 0 40 65 5 92 171 22 142 186 16 58 66 48 33 124 73 Chr. type MIC? MIC MIC? MIC? MIC? MIC? MIC? MIC MIC? MIC? MIC? MIC? MIC MIC MIC MIC MIC MIC? MIC MIC MIC MIC? MIC MIC MAC, macrochromosomes; MIC, microchromosomes. in situ hybridization. In particular, linkage groups have now been assigned to macrochromosomes 1 through 8, Z, and W. Specific physical clones (that is, cosmid, PI bacteriophage artificial chromosome, and bacterial artificial chromosome [BAC1] clones) are being used to integrate the genetic and physical maps of microchromosomes. Using 2-color fluorescent in situ hybridization (FISH1), it has been possible to differentiate 16 of the 30 microchromosomes (Fillon and others 1996a,b). It should be possible to define all microchromosomes using a set of reference probes within the next 3 yr. A World Wide Web (WWW1) page is maintained at the Roslin Institute (Edinburgh, United Kingdom) as part of the European CHICKMAP project to share information and probes for physical mapping (Jacqueline Smith, http://www.ri.bbsrc.ac.uk/). This site currently contains information on more than 214 physically mapped clones. It is our aim to assign and orient all genetic linkage groups to specific macro- or microchromosomes. An example is the integration of the genetic and physical maps of chromosome 5 shown in Figure 1. Numerous laboratories around the world have or are in the process of developing physical resources for physical map building and gene isolation as shown in Table 5. The yeast artificial chromosome (YAC1) and cosmid clones are 232 available on gridded nylon filters from the Berlin Genome Centre (http://www.rpd.de/). Comparative Gene Map The ultimate map is the DNA sequence itself. In the Human Genome Project, the entire DNA sequence of the human genome is expected to be complete by 2003. Sequencing the entire genome is not a priority in poultry and other livestock species; however, comparisons between human and poultry maps will provide links to the human DNA sequence. With many genes now mapped in the chicken, it is possible to make comparisons between the maps of chickens and mammals (Andersson and others 1996; Burt and others 1995, 1997; Girard-Santosuosso and others 1997; Jones and others 1997; Smith and others 1996, 1997). An example is a comparison of chicken chromosome 3 and its human and mouse homologous chromosomes (Table 6). Such comparisons will make it possible both to deduce the evolution of the vertebrate genome and to infer gene assignments to specific chromosomes. At the time of this writing, 220 conserved genes have been mapped in the chicken, and the following comparative data have been recorded (D. W. Burt, Roslin InstiILAR Journal 1.1 COM0016 COM0015 LEI0082-RDL0247 RDL0253 RDI_0008- f 1 S U 0 0 0 1 COM0013-LE10077^riCU0038 COM0012-.COri0156 HUJ0007 RYR3-LEI0109=fiDL0312COM0089E COri0070 MCU0029 COM0089E RDL0233-DNCL« MCW0081-DNCL-RDL0233 MCU0026 RDL0166 -COri0125E FIGURE 1 Integration of genetic and physical maps of chromosome 5 (Arkdb-CHICK, October 1998). tute, 1998, unpublished): 69 human-chicken and 92 mousechicken chromosome homologies (1 or more loci); 44 human-chicken and 46 mouse-chicken conserved syntenies (2 or more loci); 44 human-chicken and 22 mouse-chicken conserved segments (2 or more uninterrupted loci). Using this sample of conserved linkage data, we have estimated the expected number of conserved segments to be 79 to 116 human-chicken, 120 to 204 mouse-chicken, and 176 mousehuman (D. W. B., Roslin Institute, 1998, unpublished data; DeBry and Seldin 1996). Given that 20 to 24 chromosome pairs are so frequently found in fish and mammals (Morizot 1994), we assume that the ancestral vertebrate genome probably had a karyotype consisting of approximately 24 chromosome pairs. If true, then we can estimate the number of chromosome rearrangements since a common ancestor to be 71 human-chicken, 131 mouse-chicken, and 152 mousehuman. These results suggest that there have been extensive rearrangements during the evolution of rodent genomes at a rate far greater than that found in birds or other mammals (Andersson and others 1996; D. W. Burt, Roslin Institute, 1998, unpublished). This apparent stability of the avian genome is supported by early work on the conservation of the TABLE 5 Physical mapping resources Laboratory Country Type of library Reference Nat Bumstead Rima Zoorob CHICKMAPb UK France European Union YACa BACa, PACa BAC, cosmid Ann Gibbins Canada BAC Toye and others 1997 Zoorob and others 1996 R. Fries and M. A. M. Groenen, personal communication, 1997, 1998 Zimmer and Gibbins 1997 a BAC, bacterial artificial chromosome; PAC, P1 bacteriophage artificial chromosome; YAC, yeast artificial chromosome. As part of the European CHICKMAP project. b Volume 39, Numbers 2 and 3 1998 233 Genetic Markers TABLE 6 Conservation of synteny, segments, and gene order MYCN ODC1 GSTA2 BMP5 EEF1A FYN PLN ESR TCP! T Chicken Human Mouse 3 3 3 3 3 3 3 3 3 3 2 2 6 6 6 6 6 6 6 6 12 12 9 9 4 10 10 10 17 17 46 55 76 86 95 117 125 157 158 161 p24.3 p25 pi 2 q12-q13 q14 q21 q22.1 q25.1 q25-q27 q27 4 6 43 42 Sa 23 S 10 8 4 S, mapped using synteny data. avian karyotype (Tegelstrom and others 1983). The high degree of conservation found between the gene maps of the human and the chicken has great practical and evolutionary significance for the chicken and other vertebrate genomes. Recently, Groenen and coworkers (Ruyter-Spira and others forthcoming) have taken advantage of the comparative map to identify a candidate gene for a single gene mutation, autosomal dwarfism (ADW1), a recessive mutation that results in reduced adult body weight. Using bulked segregant analysis with microsatellite markers, the ADW locus was localized to chromosome 1. This particular region shares a conserved segment with mouse chromosome 10, which is significant because in mouse, a mutant phenotype, pygmy, is similar and maps to this region. Since the pygmy phenotype is the result of a mutation in the high mobility group protein I-C (HMGI-C1), it is a very good candidate gene for the ADW chicken mutant. This hypothesis is supported by physical mapping of the chicken HMGI-C gene to the same location as the microsatellite that is linked to ADW. Another example of using comparative QTL mapping is the recent, published study on Salmonella resistance in species as distantly related as mouse and chicken (Hu and others 1997). This study identified the genes NRAMP1 and TNC as genes that could account for one third of the early differential resistance to infection with Salmonella in the chicken. A realistic goal for the next 5 yr is to achieve an average marker density of 1 to 2 cM. The accomplishment of this goal will require 3000 or more markers to be placed on a framework map. With more than 1500 unique markers already scored on 1 or more of the chicken genetic maps, we are already halfway toward this goal. In addition to increasing the number of markers, the selected markers should have a high level of utility (greater than 70% heterozygosity). One common problem of all the maps is that of marker order. To resolve this dilemma, markers must be pooled into "bins." The order of the bins can be determined, and hopefully, increases in the number of meiotic breakpoints (for genetic linkage mapping) or radiation-induced breakpoints (for radiation hybrids) will minimize the size of these bins for greater accuracy. The large resource populations currently being used for QTL mapping with 500 to 2000 progeny will also help to resolve these closely linked markers. Microsatellite markers are ideal for whole genome scans; however, their numbers are limited in birds and are often 10fold less abundant than in humans (Primmer and others 1997). For high-resolution mapping, it will be necessary to use other marker types, such as amplified fragment length polymorphisms (Vos and others 1995) and single nucleotide polymorphisms (Kruglyak 1997). Comparative Map A natural outcome of mapping more type I markers onto the genetic map will be a higher resolution comparative map. A realistic goal in the next 5 yr is to map at least 2000 markers of genes with human homologues. Faster ways of mapping genes are needed and might result, for example, in increased use of FISH and radiation hybrids. In addition, the use of fiber-FISH may help to resolve gene order on the microchromosomes, often difficult by genetic linkage because of the large number of progeny needed to detect the rare recombinants on these small chromosomes. Comparative maps between different avian species should be possible by ZOOFISH, using sorted or microdissected chromosomes. It may even be possible to compare chicken and human chromosomes by ZOO-FISH. ANTICIPATED FUTURE CONTRIBUTIONS OF THE MAP Integration of Genetic and Physical Maps The chicken is an ideal livestock species for QTL studies since the relatively short generation time, the ability to produce large families, and the relatively low rearing costs are all very favorable characteristics. With the development of the first generation molecular maps, large-insert libraries, and databases, the chicken genome project has made significant progress in spite of the limited number of investigators and limited monetary resources. However, despite initial successes, much remains to be accomplished. Efforts will continue to integrate the East Lansing, Compton, and Wageningen genetic maps. All the data are or will be available on Arkdb-CHICK (http://www.ri.bbsrc.ac.uk/). Determination of genetic map completeness and identification of the microchromosome-associated linkage groups must come from the integration of the physical and genetic maps. Extended physical contig maps may be achievable for some portions of the map given the expected 3000 or more markers on the genetic map. If we assume that each cM is -400 kb 234 ILAR Journal or 1 YAC in length, then many regions may have marker densities of 1 cM or less that are amenable to contig building. Physical Resources Gridded bacterial artificial chromosome (BAC1) libraries have been produced and are now available (contact: Martien [email protected] or http://www.zod.wau.nl/ vf/chickensite/chicken.html). Chromosome-specific libraries produced by chromosome sorting or microdissection will be available for marker isolation and ZOO-FISH studies. Efforts are under way to create radiation hybrid panels for high throughput gene mapping. Bioinformatics Access to marker and map information will continue to be provided by the ARKdb-CHICK genome database. This site is under continuous development and will provide access to other marker and map types, such as radiation hybrid maps and physical contigs based on YAC and BAC clones. Links to sequence databases will be improved to provide database searches for gene homologies. Genetic Maps of Other Avian Species A project to produce a microsatellite map of the turkey genome began in April 1997 as a collaboration between the Roslin Institute and British United Turkeys. This map will be made available to interested groups in the same way as has been done with the chicken reference families (DNA, databases, and so forth). We hope that maps on other species (such as quail and ducks) will also be started for developing comparative maps among avian species. USES OF THE MAP AND ACCESSIBILITY Genome projects are inherently more efficient when they are the result of group effort, coordinated primarily through formal projects, shared resources and information, and joint meetings. In Europe, the Economic Community has funded a CHICKMAP project, started in early 1996 under the coordination of Dave Burt (Roslin Institute). This group aims to develop tools and resources for QTL mapping in poultry (genetic markers and maps, physical maps and resources, comparative maps, and genome databases), as well as to integrate the strengths of many laboratories involved in chicken genomics. Information on genetic markers, genetic maps, physical maps, and so forth are provided free from the CHICKMAP WWW pages (http://www.ri.bbsrc.ac.uk). Physical resources such as filters of gridded cosmid and YAC clones are being distributed by the Berlin Genome Centre Volume 39, Numbers 2 and 3 1998 (http://www.rzpd.de/). A gridded BAC library is also available (address provided in Physical Resources). In the United States, East Lansing serves as the Poultry Coordination Center of the National Animal Genome Research Program. Besides distributing the East Lansing reference family, microsatellite primer kits are also distributed. Currently, there is a "Population Tester Kit" containing fluorescently labeled primers to amplify 9 highly polymorphic microsatellites and intended for use in other avian species or first-time users of microsatellite markers. The ability to obtain informative markers in other avian species has been variable and is probably dependent on the genetic distance from chicken. Additionally, 3 "Comprehensive Mapping Kits" contain fluorescently labeled primers for more than 500 microsatellite markers roughly spaced over the entire chicken genome. Databases are the main vehicles for sharing scientific information. The bioinformatics group at the Roslin Institute has developed a generic livestock genome database, ARKdb (Archibald and others 1996), with the chicken as one of the represented species. Using the Internet, researchers can access information on maps, markers, sequences, references, and so forth through a graphic interface (http:// www.ri.bbsrc.ac.uk/). The Roslin site is linked to the East Lansing site, which also maintains a WWW site (http:// poultry.mph.msu.edu) that contains the latest East Lansing map and other marker information. These 2 sites, as well as many others, are linked and are readily accessed on the WWW. Regular meetings (such as the 1998 Plant and Animal Genome meeting in San Diego, California, and the 1998 International Society of Animal Genetics meeting in New Zealand), newsletters (such as Poultry Genome Newsletter), and electronic bulletin boards (such as ANGENMAP) also provide effective sources of information. CONCLUSION The chicken genome project has achieved its initial goals, and it appears that the momentum will continue in the foreseeable future. ACKNOWLEDGMENTS We thank the many colleagues and sponsors engaged in the various multinational collaborations to map the genomes of poultry. Genome research at the Roslin Institute is supported by funds from the Ministry of Agriculture, Fisheries and Food, the Biotechnology Sciences Research Council, and the Commission of the European Communities. H. H. C. is supported by the US Department of Agriculture (USDA) Agricultural Research Service and grants from the USDA, the US-Israel Binational Research and Development Fund, and the US-Israel Binational Science Foundation. The USDA also provides financial support for public resources. 235 REFERENCES Andersson L, Ashburner M, Audun S, Barendse W, Bitgood J, Bottema C, Broad T, Brown S, Burt D, Charleir C, Copeland N, Davis S, Davisson M, Edwards J, Eggene A, Elgar G, Eppig J, Franklin I, Grewe P, Gill T, Graves J, Hawken R, Hetzel J, Hillyard A, Jacob H, Jaswinska L, Jenkins N, Kunz H, Levan G, Lie O, Lyons L, Maccarone P, Mellersh C, Montgomery G, Moore S, Moran C, Morizot D, Neff M, Nicholas F, O'Brien S, Parsons Y, Peters J, Postlethwait J, Raymond M, Rothschild M, Schook L, Sugimoto Y, Szpirer C, Tate M, Taylor J, VandeBerg J, Wakefield M, Weinberg J, Womack J. 1996. Comparative Genome Organization of Vertebrates: The First International Workshop on Comparative Genome Organization. Mamm Genome 7:717-734. Archibald AL, Hu J, Mungall C, Hillyard AL, Burt DW, Law AS, Nicholson D. 1996. A generic single species genome database. Proceedings of the 25th International Conference on Animal Genetics, Tours, 21-25 July, Abstract COOL Bitgood JJ, Shoffner RN. 1990. Cytology and cytogenetics. In: Crawford RD, editor. Poultry Breeding and Genetics. Amsterdam: Elsevier. p 401-427. Bitgood JJ, Somes Jr RG. 1993. Gene map of the chicken {Gallus gallus or G. domesticus). In: O'Brien SJ, editor. Genetic Maps, 6th edition. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, p 4.332-4.342. Bloom SE, Delany ME, Muscarella DE. 1993. Constant and variable features of avian chromosomes. In: Etches RJ, Gibbins AMV, editors. Manipulation of the Avian Genome. Florida: CRC Press, p 39-59. Bumstead N, Palyga J. 1992. A preliminary linkage map of the chicken genome. Genomics 13:690-697. Burt DW, Bumstead N, Bitgood JJ, Ponce de Leon FA, Crittenden LB. 1995. Chicken genome mapping: A new era in avian genetics. Trends Genet 11:190-194. Burt DW, Bumstead N, Burke T, Fries R, Groenen MAM, Tixier-Boichard M, Vignal A. 1997. Current status of poultry genome mapping—June 1997. Proceedings of the 12th AVIAGEN Symposium: Current Problems in Avian Genetics, p 33-45. Cheng HH, Crittenden LB. 1994. Microsatellite markers for genetic mapping in the chicken. Poult Sci 73:539-546. Cheng HH, Levin I, Vallejo RL, Khatib H, Dodgson JB, Crittenden LB, Hillel J. 1995. Development of a genetic map of the chicken with markers of high utility. Poult Sci 74:1855-1874. Crawford RD. 1990. Poultry Breeding and Genetics. Amsterdam: Elsevier. Crittenden LB. Provencher L, Santangelo L, Levin I, Abplanalp H, Briles RW, Briles WE, Dodgson JB. 1993. Characterization of a Red Jungle Fowl by White Leghorn backcross reference population for molecular mapping of the chicken genome. Poult Sci 72:334-348. Crooijmans RPMA, Van Oers PAM, Strijk JA, Van Der Poel JJ, Groenen MAM. 1996. Preliminary linkage map of the chicken {Gallus domesticus) genome based on microsatellite markers: 77 new markers mapped. Poult Sci 75:746-754. Crooijmans RPMA, Dijkhof RJM, van der Poel JJ, Groenen MAM. 1997. New microsatellite markers in chicken optimized for automated fluorescent genotyping. Anim Genet 28:427-437. DeBry RW, Seldin MF. 1996. Human/mouse homology relationships. Genomics 33:337-351. Fillon V, Morisson M, Zoorob R, Auffray C, Douaire M, Vignal A. 1996a. Labelling of chicken microchromosomes by molecular markers using two-color fluorescence in situ hybridization (FISH). Arch Zootec 45:303-307. Fillon V, Zoorob R, Yerle M, Auffray C, Vignal A. 1996b. Mapping of the genetically independent chicken major histocompatibility complexes B® and RFP-Y® to the same microchromosome by two-color fluorescent in 236 situ hybridization. Cytogenet Cell Genet 75:7-9. Gibbs M, Dawson DA, McCamley C, Wardle AF, Armour JAL, Burke T. 1997. Chicken microsatellite markers isolated from libraries enriched for simple tandem repeats. Anim Genet 28:401-417. Girard-Santosuosso O, Bumstead N, Lantier I, Protais J, Colin P, Guillot JF, Beaumont C, Malo D, Lantier F. 1997. Partial conservation of the mammalian NRAMP1 syntenic group on chicken chromosome 7. Mamm Genome 8:614-616. Hu J, Bumstead N, Barrow P, Sebastiani G, Olien L, Morgan K, Malo D. 1997. Resistance to salmonellosis in the chicken is linked to NRAMP1 and TNC. Genome Res 7:693-704. Hutt FB. 1936. Genetics of the fowl. VI. A tentative chromosome map. Neue Forsch Tiersucht Abstain (Duerst Festschrift), p 105-112. Jones CT, Morrice DR, Paton IR, Burt DW. 1997. Gene homologues on human chromosome 15q21 -q26 and a chicken microchromosome identify a new conserved segment. Mamm Genome 8:436-440. Kosambi DD. 1944. The estimation of the map distance from recombination values. Ann Eugen 12:172-175. Kruglyak L. 1997. The use of a genetic map of biallelic markers in linkage studies. Nat Genet 17:21-24. Morizot DC. 1994. Reconstructing the gene map of the vertebrate ancestor. Anim Biotechnol 5:113-122. Morton NE. 1991. Parameters of the human genome. Proc Natl Acad Sci U S A 88:7474-7476. Ponce de Leon FA, Bitgood JJ, Ladjadi K, Tixier-Boichard M. 1993. International Committee for the Standardization of the Avian (ICSAK) Karyotype. 8th North American Colloquium on Domestic Animals Cytogenetics and Gene Mapping, Guelph, Ontario, Canada, July 12-16. Primmer CR, Raudsepp T, Chowdhary BP, Moller AP, Ellegren H. 1997. Low frequency of microsatellites in the avian genome. Genome Res 7:471-482. Rodionov AV, Myakoshina YA, Chelysheva LA, Solovei IV, Gaginskaya ER. 1992. Chiasmata on lampbrush chromosomes of Gallus gallus domesticus: A cytogenetic study of recombination frequency and linkage group lengths. Genetika 28:53-63. Ruyter-Spira CP, de Groof AJ, van der Poel JJ, Herbergs J, Masabanda J, Fries R, Groenen MA. 1998. The HMGl-C gene is a likely candidate for the autosomal dwarf locus in the chicken. J Hered 89:295-300. Smith EJ, Cheng HH, Vallejo RL. 1996. Mapping functional chicken genes: An alternative approach. Poult Sci 75:642-647. Smith EJ, Lyons LA, Cheng HH, Suchyta SP. 1997. Comparative mapping of the chicken genome using the East Lansing reference population. Poult Sci 76:743-747. Smith J, Burt DW. 1998. Parameters of the chicken genome (Gallus gallus). Anim Genet 29:290-294. Tegelstrom H, Ebenhard T, Ryttman H. 1983. Rate of karyotype evolution and speciation in birds. Hereditas 98:235-239. Toye AA, Schalkwyk L, Lehrach H, Bumstead N. 1997. A yeast artificial chromosome (YAC) library containing 10 haploid chicken genome equivalents. Mamm Genome 8:274-276. Vos P, Hogers R, Bleeker M, Reijans M, Van de Lee T, Homes M, Frijters A, Pot J, Peleman J, Kuiper M, Zabeau M. 1995. AFLP: A new technique for DNA fingerprinting. Nucleic Acids Res 21:4407-4414. Zimmer R, Gibbins AMV. 1997. Construction and characterization of a large-fragment chicken bacterial artificial chromosome library. Genomics 42:217-226. Zoorob R, Billault A, Severac V, Fillon V, Vignal A, Auffray C. 1996. Two chicken genomic libraries in the PAC and BAC cloning systems: Organization and characterization. Proceedings of the 25th International Conference on Animal Genetics, Tours, 21-25 July, Abstract C055. ILAR Journal