A second-generation genetic linkage map of the baboon (Papio hamadryas) genome

Construction of genetic linkage maps for nonhuman primate species provides information and tools that are useful for comparative analysis of chromosome structure and evolution and facilitates comparative analysis of meiotic recombination mechanisms. Most importantly, nonhuman primate genome linkage maps provide the means to conduct whole genome linkage screens for localization and identification of quantitative trait loci that influence phenotypic variation in primate models of common complex human diseases such as atherosclerosis, hypertension, and diabetes. In this study we improved a previously published baboon whole genome linkage map by adding more loci. New loci were added in chromosomal regions that did not have sufficient marker density in the initial map. Relatively low heterozygosity loci from the original map were replaced with higher heterozygosity loci. We report in detail on baboon chromosomes 5, 12, and 18 for which the linkage maps are now substantially improved due to addition of new informative markers.     

Second-generation integrated genetic linkage/radiation hybrid maps of the domestic cat (Felis catus)

We report construction of second-generation integrated genetic linkage and radiation hybrid (RH) maps in the domestic cat (Felis catus) that exhibit a high level of marker concordance and provide near-full genome coverage. A total of 864 markers, including 585 coding loci (type I markers) and 279 polymorphic microsatellite loci (type II markers), are now mapped in the cat genome. We generated the genetic linkage map utilizing a multigeneration interspecies backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis). Eighty-one type I markers were integrated with 247 type II markers from a first-generation map to generate a map of 328 loci (320 autosomal and 8 X-linked) distributed in 47 linkage groups, with an average intermarker spacing of 8 cM. Genome coverage spans approximately 2,650 cM, allowing an estimate for the genetic length of the sex-averaged map as 3,300 cM. The 834-locus second-generation domestic cat RH map was generated from the incorporation of 579 type I and 255 type II loci. Type I markers were added using targeted selection to cover either genomic regions underrepresented in the first-generation map or to refine breakpoints in human/feline synteny. The integrated linkage and RH maps reveal approximately 110 conserved segments ordered between the human and feline genomes, and provide extensive anchored reference marker homologues that connect to the more gene dense human and mouse sequence maps, suitable for positional cloning applications.     

A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms

A first-generation genetic linkage map of the baboon (Papio hamadryas) genome was developed for use in biomedical and evolutionary genetics. Pedigreed baboons (n = 694) were selected from the breeding colony maintained by the Southwest Foundation for Biomedical Research. To facilitate comparison with the human genome, the baboon linkage map consists primarily of human microsatellite loci amplified using published human PCR primers. Genotypes for 325 human microsatellites and 6 novel baboon microsatellites were used in linkage analyses performed with the MultiMap expert system. The resulting sex-averaged meiotic recombination map covers all 20 baboon autosomes, with average spacing among loci of 7.2 cM. Direct comparison among homologous (orthologous) loci reveals that, for 7 human autosomes, locus order is conserved between humans and baboons. For the other 15 autosomes, one or more rearrangements distinguish the two genomes. The total centimorgan distances among homologous markers are 28.0% longer in the human genome than in the baboon, suggesting that rates of recombination may be higher in humans. This baboon linkage map is the first reported for any nonhuman primate species and creates opportunities for mapping quantitative trait loci in baboons, as well as for comparative evolutionary analyses of genome structure.     

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     

An initial genetic linkage map of the rhesus macaque (Macaca mulatta) genome using human microsatellite loci

Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate species in biomedical research. To create new opportunities for genetic and genomic studies using rhesus monkeys, we constructed a genetic linkage map of the rhesus genome. This map consists of 241 microsatellite loci, all previously mapped in the human genome. These polymorphisms were genotyped in five pedigrees of rhesus monkeys totaling 865 animals. The resulting linkage map covers 2048 cM including all 20 rhesus autosomes, with average spacing between markers of 9.3 cM. Average heterozygosity among those markers is 0.73. This linkage map provides new comparative information concerning locus order and interlocus distances in humans and rhesus monkeys. The map will facilitate whole-genome linkage screens to locate quantitative trait loci (QTLs) that influence individual variation in phenotypic traits related to basic primate anatomy, physiology, and behavior, as well as QTLs relevant to risk factors for human disease.     

Piggy-BACing the human genome II. A high-resolution, physically anchored, comparative map of the porcine autosomes

Using the INRA-Minnesota porcine radiation hybrid panel, we have constructed a human-pig comparative map composed of 2274 loci, including 206 ESTs and 2068 BAC-end sequences, assigned to 34 linkage groups. The average spacing between comparative anchor loci is 1.15 Mb based on human genome sequence coordinates. A total of 51 conserved synteny groups that include 173 conserved segments were identified. This radiation hybrid map has the highest resolution of any porcine map to date and its integration with the porcine linkage map (reported here) will greatly facilitate the positional cloning of genes influencing complex traits of both agricultural and biomedical interest. Additionally, this map will provide a framework for anchoring contigs generated through BAC fingerprinting efforts and assist in the selection of a BAC minimal tiling path and assembly of the first sequence-ready map of the porcine genome.     

Construction of a genetic linkage map in man using restriction fragment length polymorphisms.

We describe a new basis for the construction of a genetic linkage map of the human genome. The basic principle of the mapping scheme is to develop, by recombinant DNA techniques, random single-copy DNA probes capable of detecting DNA sequence polymorphisms, when hybridized to restriction digests of an individual's DNA. Each of these probes will define a locus. Loci can be expanded or contracted to include more or less polymorphism by further application of recombinant DNA technology. Suitably polymorphic loci can be tested for linkage relationships in human pedigrees by established methods; and loci can be arranged into linkage groups to form a true genetic map of "DNA marker loci." Pedigrees in which inherited traits are known to be segregating can then be analyzed, making possible the mapping of the gene(s) responsible for the trait with respect to the DNA marker loci, without requiring direct access to a specified gene's DNA. For inherited diseases mapped in this way, linked DNA marker loci can be used predictively for genetic counseling.     

Development and applications of a molecular genetic linkage map of the mouse genome

Interspecific mouse backcrosses provide almost limitless genetic variation for gene mapping. We have used interspecific backcrosses to develop the first comprehensive molecular genetic linkage map of the mouse genome. More than 600 loci have been positioned on the map; the current average map resolution is less than 3 cM. Since all loci were mapped using a single backcross panel, gene order can be determined unambiguously. With this level of resolution, it is now possible to position any new locus on the linkage map with virtually 100% certainty. In this article, we review how interspecific linkage maps are constructed, the salient features of our linkage map, and some of the many applications of interspecific linkage maps, in general, for future research.     

A predicted microsatellite map of the passerine genome based on chicken-passerine sequence similarity

Abstract We present a predicted passerine genome map consisting of 196 microsatellite markers distributed across 25 chromosomes. The map was constructed by assigning chromosomal locations based on the sequence similarity between 550 publicly available passerine microsatellites and the draft chicken genome sequence published by the International Chicken Genome Sequencing Consortium. We compared this passerine microsatellite map with a recently published great reed warbler (Acrocephalus arundinaceus) linkage map derived from the segregation of marker alleles in a pedigree of a natural population. Twenty-four microsatellite markers were shared between the two maps, distributed across ten chromosomes. Synteny was maintained between the predicted passerine microsatellite map and the great reed warbler linkage map, confirming the validity and accuracy of our approach. Possible applications of the predicted passerine microsatellite map include genome mapping; quantitative trait locus (QTL) discovery; understanding heterozygosity-fitness correlations; investigating avian karyotype evolution; understanding microsatellite mutation processes; and for identifying loci conserved in multiple species, unlinked loci for use in genotyping sets and sex-linked markers.     

An integrated and comparative genetic map of the turkey genome

An integrated genetic linkage map was developed for the turkey (Meleagris gallopavo) that combines the genetic markers from the three previous mapping efforts. The UMN integrated map includes 613 loci arranged into 41 linkage groups. An additional 105 markers are tentatively placed within linkage groups based on two-point LOD scores and 19 markers remain unlinked. A total of 210 previously unmapped markers has been added to the UMN turkey genetic map. Markers from each of the 20 linkage groups identified in the Roslin map and the 22 linkage groups of the Nte map are incorporated into the new integrated map. Overall map distance contained within the 41 linkage groups is 3,365 cM (sex-averaged) with the largest linkage group (94 loci) measuring 533.1 cM. Average marker interval for the map was 7.86 cM. Sequences of markers included in the new map were compared to the chicken genome sequence by 'BLASTN'. Significant similarity scores were obtained for 95.6% of the turkey sequences encompassing an estimated 91% of the chicken genome. A physical map of the chicken genome based on positions of the turkey sequences was built and 36 of the 41 turkey linkage groups were aligned with the physical map, five linkage groups remain unassigned. Given the close similarities between the turkey and chicken genomes, the chicken genome sequence could serve as a scaffold for a genome sequencing effort in the turkey.     

A comparative genetic map of the turkey genome

Genetic markers (microsatellites and SNPs) were used to create and compare maps of the turkey and chicken genomes. A physical map of the chicken genome was built by comparing sequences of turkey markers with the chicken whole-genome sequence by BLAST analysis. A genetic linkage map of the turkey genome (Meleagris gallopavo) was developed by segregation analysis of genetic markers within the University of Minnesota/Nicholas Turkey Breeding Farms (UMN/NTBF) resource population. This linkage map of the turkey genome includes 314 loci arranged into 29 linkage groups. An additional 40 markers are tentatively placed within linkage groups based on two-point LOD scores and 16 markers remain unlinked. Total map distance contained within linkage groups is 2,011 cM with the longest linkage group (47 loci) measuring 413.3 cM. Average marker interval over the 29 linkage groups was 6.4 cM. All but one turkey linkage group could be aligned with the physical map of the chicken genome. The present genetic map of the turkey provides a comparative framework for future genomic studies.     

A genetic linkage map of microsatellites in the domestic cat (Felis catus)

Of the nonprimate mammalian species with developing comparative gene maps, the feline gene map (Felis catus, Order Carnivora, 2N = 38) displays the highest level of syntenic conservation with humans, with as few as 10 translocation exchanges discriminating the human and feline genome organization. To extend this model, a genetic linkage map of microsatellite loci in the feline genome has been constructed including 246 autosomal and 7 X-linked loci. Two hundred thirty-five dinucleotide (dC. dA)n. (dG. dT)n and 18 tetranucleotide repeat loci were identified and genotyped in a two-family, 108-member multigeneration interspecies backcross pedigree between the domestic cat (F. catus) and the Asian leopard cat (Prionailurus bengalensis). Two hundred twenty-nine loci were linked to at least one other marker with a lod score >/=3.0, identifying 34 linkage groups. Representative markers from each linkage group were assigned to specific cat chromosomes by somatic cell hybrid analysis, resulting in chromosomal assignments to 16 of the 19 feline chromosomes. Genome coverage spans approximately 2900 cM, and we estimate a genetic length for the sex-averaged map as 3300 cM. The map has an average intragroup intermarker spacing of 11 cM and provides a valuable resource for mapping phenotypic variation in the species and relating it to gene maps of other mammals, including human.     

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.     

A Genetic Linkage Map for Cattle

We report the most extensive physically anchored linkage map for cattle produced to date. Three-hundred thirteen genetic markers ordered in 30 linkage groups, anchored to 24 autosomal chromosomes (n = 29), the X and Y chromosomes, four unanchored syntenic groups and two unassigned linkage groups spanning 2464 cM of the bovine genome are summarized. The map also assigns 19 type I loci to specific chromosomes and/or syntenic groups and four cosmid clones containing informative microsatellites to chromosomes 13, 25 and 29 anchoring syntenic groups U11, U7 and U8, respectively. This map provides the skeletal framework prerequisite to development of a comprehensive genetic map for cattle and analysis of economic trait loci (ETL).     

Construction of an oilseed rape (Brassica napus L.) genetic map with SSR markers

We constructed a Brassica napus genetic map with 240 simple sequence repeats (SSR) primer pairs from private and public origins. SSR, or microsatellites, are highly polymorphic and efficient markers for the analysis of plant genomes. Our selection of primer pairs corresponded to 305 genetic loci that we were able to map. In addition, we also used 52 sequence-characterized amplified region primer pairs corresponding to 58 loci that were developed in our lab. Genotyping was performed on six F2 populations, corresponding to a total of 574 F2 individual plants, obtained according to an unbalanced diallel cross design involving six parental lines. The resulting consensus map presented 19 linkage groups ranging from 46.2 to 276.5 cM, which we were able to name after the B. napus map available at , thus enabling the identification of the A genome linkage groups originating from the B. rapa ancestor and the C genome linkage groups originating from the B. oleracea ancestor in the amphidiploid genome of B. napus. Some homoeologous regions were identified between the A and the C genomes. This map could be used to identify more markers, which would eventually be linked to genes controlling important agronomic characters in rapeseed. Furthermore, considering the good genome coverage we obtained, together with an observed homogenous distribution of the loci across the genome, this map is a powerful tool to be used in marker-assisted breeding. Electronic Supplementary Material Supplementary material is available for this article at     

A molecular linkage map of olive (Olea europaea L) based on RAPD, microsatellite, and SCAR markers.

An integrated molecular linkage map of olive (Olea europaea L.) was constructed based on randomly amplified polymorphic DNA (RAPD), sequence characterized amplified region (SCAR), and microsatellite markers using the pseudo-testcross strategy. A mapping population of 104 individuals was generated from an F1 full-sib family of a cross between 'Frantoio' and 'Kalamata'. The hybridity of the mapping population was confirmed by genetic similarity and nonmetric multidimensional scaling. Twenty-three linkage groups were mapped for 'Kalamata', covering 759 cM of the genome with 89 loci and an average distance between loci of 11.5 cM. Twenty-seven linkage groups were mapped for 'Frantoio', covering 798 cM of the genome with 92 loci and an average distance between loci of 12.3 cM. For the integrated map, 15 linkage groups covered 879 cM of the genome with 101 loci and an average distance between loci of 10.2 cM. The size of the genomic DNA was estimated to be around 3000 cM. A sequence characterized amplified region marker linked to olive peacock disease resistance was mapped to linkage group 2 of the integrated map. These maps will be the starting point for studies on the structure, evolution, and function of the olive genome. When the mapping progeny pass through their juvenile phase and assume their adult characters, mapping morphological markers and identification of quantitative trait loci for adaptive traits will be the primary targets.     

A molecular linkage map of cultivated oat.

A molecular linkage map of cultivated oat composed of 561 loci has been developed using 71 recombinant inbred lines from a cross between Avena byzantina cv. Kanota and A. sativa cv. Ogle. The loci are mainly restriction fragment length polymorphisms detected by oat cDNA clones from leaf, endosperm, and root tissue, as well as by barley leaf cDNA clones. The loci form 38 linkage groups ranging in size from 0.0 to 122.1 cM (mean, 39 cM) and consist of 2-51 loci each (mean, 14). Twenty-nine loci remain unlinked. The current map size is 1482 cM and the total size, on the basis of the number of unlinked loci, is estimated to be 2932.0 cM. This indicates that this map covers at least 50% of the cultivated oat genome. Comparisons with an A-genome diploid oat map and between linkage groups exhibiting homoeology to each other indicate that several major chromosomal rearrangements exist in cultivated oat. This map provides a tool for marker-assisted selection, quantitative trait loci analyses, and studies of genome organization in oat.     

A radiation hybrid map of bovine X Chromosome (BTAX)

We present a comprehensive radiation hybrid map of the bovine X chromosome (Chr) containing 20 new markers, including both microsatellites and expressed genes. This study was conducted with a 5000-rad whole genome RH cell panel consisting of 90 hybrid cell lines. Retention frequencies of individual markers range from 7.8% for XIST to 31.1% for TGLA325. Statistical analysis with RHMAPPER placed all the loci into five linkage groups under a LOD score criterion of 6.0. These groups could be oriented relative to each other because they included multiple microsatellite loci from the consensus linkage map of the X Chr. Markers included in both this RH map and the bovine cytogenetic map were in a consistent order. The comparative bovine–human map thus generated consists of five blocks of genes, the order of which is conserved, although in the opposite direction when presented as ideograms with p and q arms. Inversions of three blocks account for the difference in gene order across the entirety of the two X Chrs.     

A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content

We have developed a new DH mapping population for oilseed rape, named TNDH, using genetically and phenotypically diverse parental lines. We used the population in the construction of a high stringency genetic linkage map, consisting of 277 loci, for use in quantitative genetic analysis. A proportion of the markers had been used previously in the construction of linkage maps for Brassica species, thus permitting the alignment of maps. The map includes 68 newly developed Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of A. thaliana. The use of these markers permits the alignment of our linkage map with the A. thaliana genome sequence. An additional 74 loci (31 newly developed STS markers and 43 loci defined by SSR and RFLP markers that had previously been used in published linkage maps) were added to the map. These markers increased the resolution of alignment of the newly constructed linkage map with existing Brassica linkage maps and the A. thaliana genome sequence. We conducted field trials with the TNDH population at two sites, and over 2 years, and identified reproducible QTL for seed oil content and erucic acid content. The results provide new insights into the genetic control of seed oil and erucic acid content in oilseed rape, and demonstrate the utility of the linkage map and population.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.D. Qiu and C. Morgan authors contributed equally to the work.     

Integration of the feline radiation hybrid and linkage maps

The recent development of genome mapping resources for the domestic cat provides a unique opportunity to study comparative medicine in this companion animal which can inform and benefit both veterinary and human biomedical concerns. We describe here the integration and order comparison of the feline radiation hybrid (RH) map with the feline interspecies backcross (ISB) genetic linkage map, constructed by a backcross of F₁ hybrids between domestic cat (Felis catus) and the Asian leopard cat (Prionailurus bengalensis). Of 253 microsatellite loci mapped in the ISB, 176 equivalently spaced markers were ordered among a framework of 424 Type I coding markers in the RH map. The integration of the RH and ISB maps resolves the orientation of multiple linkage groups and singleton loci from the ISB genetic map. This integrated map provides the foundation for gene mapping assessments in the domestic cat and in related species of the Felidae family. Received: 10 July 2000 / Accepted: 01 February 2001