Mining the 99 Lives Cat Genome Sequencing Consortium database implicates genes and variants for the Ticked locus in domestic cats (Felis catus).

Tabby patterns of fur coats are defining characteristics in wild and domestic felids. Historically, three autosomal alleles at one locus (Tabby): Abyssinian (Ta ; a.k.a. ticked), mackerel (Tm ; a.k.a. striped) and blotched (tb ; a.k.a. classic, blotched) were thought to control these patterns in domestic cats and their breeds. Currently, at least three loci influence cat tabby markings, two of which are designated Tabby and Ticked. The Tabby locus is laeverin (LVRN) and affects the mackerel and blotched patterns. The unidentified gene for the Ticked locus on cat chromosome B1 was suggested to control the presence or absence of the ticked pattern (Tabby - Abyssinian (Ta ; a.k.a. ticked). The cat reference genome (Cinnamon, the Abyssinian) has the ticked phenotype and the variant dataset and coat phenotypes from the 99 Lives Cat Genome Consortium (195 cats) were used to identify candidate genes and variants associated with the Ticked locus. Two strategies were used to find the Ticked allele(s), one considered Cinnamon with the reference allele or heterozygous (Strategy A) and the other considered Cinnamon as having the variant allele or heterozygous (Strategy B). For Strategy A, two variants in Dickkopf Wnt Signaling Pathway Inhibitor 4 (DKK4), a p.Cys63Tyr (B1:41621481, c.188G>A) and a less common p.Ala18Val (B1:42620835, c.53C>T) variant are suggested as two alleles influencing the Ticked phenotype. Bioinformatic and molecular modeling analysis suggests that these changes disrupt a key disulfide bond in the Dkk4 cysteine-rich domain 1 or Dkk4 signal peptide cleavage respectively. All coding variants were excluded as Ticked alleles using Strategy B.

Standardization of a SNP panel for parentage verification and identification in the domestic cat (Felis silvestris catus).

The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, population and breed structure relationships, and individual identification for forensic and registration purposes. The International Society of Animal Genetics (ISAG) hosts the Applied Genetics in Companion Animals Workshop, which supports the standardization of genetic marker panels and genotyping for the identification of cats via comparison testing. SNP panels have been in development for many species, including the domestic cat. An ISAG approved core panel of SNPs for use in cat identification and parentage analyses is presented. SNPs (n = 121) were evaluated by different university-based and commercial laboratories using 20 DNA samples as part of the ISAG comparison testing procedures. Different SNP genotyping technologies were examined, including DNA arrays, genotyping-by-sequencing and mass spectroscopy, to select a robust and efficient panel of 101 SNPs as the ISAG core panel for cats. The SNPs are distributed across all chromosomes including two on the X chromosome and an XY pseudo-autosomal sexing marker (zinc-finger XY; ZFXY). A population study demonstrated that the markers have an average polymorphic information content of 0.354 and a power of exclusion greater than 0.9999. The SNP panel should keep testing affordable while also allowing for the development of additional panels to monitor health, phenotypic traits, hybrid cats and highly inbred cats.

Mocha tyrosinase variant: a new flavour of cat coat coloration.

A novel coloration named 'mocha' has been identified in the Burmese cat breed from Thailand. Tyrosinase (TYR) mutations are known to be associated with coat coloration in cats, such as the sable Burmese, the points of the Siamese and albino cats. Additionally, sable Burmese that produced mocha-colored cats had unexpected genotypes for TYR. Therefore, TYR was considered a candidate gene for mocha in cats. Sanger sequencing for genomic DNA revealed NC_018732.3:chromosome D1:45 898 609_45 898 771dup in exon 2 and intron 2 of TYR. Transcription analysis using cDNA detected c.820_936delinsAATCTC (p.I274_L312delinsNL), which caused a 111-bp (37 amino acid) deletion in the reading frame of TYR. The identified variant was concordant with the phenotype and segregated with TYR variants in a pedigree of 12 Burmese cats. This findings of this study suggest that TYR is associated with the mocha coloration in cats. The new color variant adds to the allelic series for TYR (C > cb  = cs  > c, c2 ) and is recessive to full color (C); however, interactions with the cb and cs alleles are unclear due to the temperature-sensitivity of the alleles.

Targeted genotyping by sequencing: a new way to genome profile the cat.

Targeted GBS is a recent approach for obtaining an effective characterization for hundreds to thousands of markers. The high throughput of next-generation sequencing technologies, moreover, allows sample multiplexing. The aims of this study were to (i) define a panel of single nucleotide polymorphisms (SNPs) in the cat, (ii) use GBS for profiling 16 cats, and (iii) evaluate the performance with respect to the inference using standard approaches at different coverage thresholds, thereby providing useful information for designing similar experiments. Probes for sequencing 230 variants were designed based on the Felis_catus_8.0. 8.0 genome. The regions comprised anonymous and non-anonymous SNPs. Sixteen cat samples were analysed, some of which had already been genotyped in a large group of loci and one having been whole-genome sequenced in the 99_Lives Cat Genome Sequencing Project. The accuracy of the method was assessed by comparing the GBS results with the genotypes already available. Overall, GBS achieved good performance, with 92-96% correct assignments, depending on the coverage threshold used to define the set of trustable genotypes. Analyses confirmed that (i) the reliability of the inference of each genotype depends on the coverage at that locus and (ii) the fraction of target loci whose genotype can be inferred correctly is a function of the total coverage. GBS proves to be a valid alternative to other methods. Data suggested a depth of less than 11× is required for greater than 95% accuracy. However, sequencing depth must be adapted to the total size of the targets to ensure proper genotype inference.

First genome-wide CNV mapping in FELIS CATUS using next generation sequencing data.

BACKGROUND: Copy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still missing in Felis catus. The present work is the first CNV mapping from a large data set of Next Generation Sequencing (NGS) data in the domestic cat, performed within the 99 Lives Consortium. RESULTS: Reads have been mapped on the reference assembly_6.2 by Maverix Biomics. CNV detection with cn.MOPS and CNVnator detected 592 CNVs. These CNVs were used to obtain 154 CNV Regions (CNVRs) with BedTools, including 62 singletons. CNVRs covered 0.26% of the total cat genome with 129 losses, 19 gains and 6 complexes. Cluster Analysis and Principal Component Analysis of the detected CNVRs showed that breeds tend to cluster together as well as cats sharing the same geographical origins. The 46 genes identified within the CNVRs were annotated. CONCLUSION: This study has improved the genomic characterization of 14 cat breeds and has provided CNVs information that can be used for studies of traits in cats. It can be considered a sound starting point for genomic CNVs identification in this species.

Not another type of potato: MC1R and the russet coloration of Burmese cats.

The Burmese is a breed of domestic cat that originated in Southeast Asia and was further developed in the United States. Variants in melanocortin 1 receptor (MC1R) causes common coat colour phenotypes in a variety of mammalian species but only limited colour variation in the domestic cat. Known as the extension (E) locus, melanocortin 1 receptor (MC1R) interacts with the agouti locus to produce the eumelanin and pheomelanin pigments. Recently, a novel reddish coloration, which is termed russet, was identified in the Burmese cat breed. Because this russet Burmese coloration changes with aging, MC1R was suggested as candidate gene. The similar colouration in specific lineages of Norwegian Forest cat known as amber (e) (c.250G>A; p.Asp84Asn) was excluded for this Burmese phenotype. The complete 954-bp coding region of MC1R was directly sequenced in russet Burmese and suspected carriers. A 3-bp deletion (c.439_441del) associated with the deletion of a phenyalanine (p.Phe146del) in the protein sequence was identified. All russet coloured cats were homozygous for the variant, and all obligate carriers were heterozygous, confirming that the deletion segregated concordantly with colouring in Burmese cats from the New Zealand foundation lineage. The variant was not identified in 442 cats from 26 different breeds and random-bred cats. Twenty-six Burmese from the USA did not have the variant. This MC1R variant defines a unique coloration and the second breed-specific MC1R variant in cats. The interactions of the two recessive feline MC1R alleles (E  >  e, er ) is unknown.

Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand.

AIMS To determine the frequency of the FAS-ligand gene (FASLG) variant associated with feline autoimmune lymphoproliferative syndrome (FALPS) and the proportion of carriers of the variant in three British shorthair (BSH) breeding catteries in New Zealand. METHODS Buccal swabs were collected from all cats in two BSH breeding catteries from the South Island and one from the North Island of New Zealand. DNA was extracted and was tested for the presence of the FASLG variant using PCR. Cats with the FASLG variant were identified and the frequency of the FASLG variant allele calculated. Pedigree analysis was performed and inbreeding coefficients were calculated for cats with the FASLG variant. RESULTS Of 32 BSH cats successfully tested for the presence of the FASLG variant, one kitten (3%) was homozygous (FALPS-affected), and seven (22%) cats were heterozygous (carriers) for the FASLG variant allele, and 24 (75%) cats were homozygous for the wild type allele. The overall frequency of the FASLG variant allele in these 32 cats was 0.14. Cats carrying the FASLG variant were from all three breeding catteries sampled, including two catteries that had not previously reported cases of FALPS. Pedigree analysis revealed common ancestry of FALPS-affected and carrier cats within six generations, as well as frequent inbreeding, with inbreeding coefficients >0.12 for five cats with the FASLG variant. CONCLUSIONS AND CLINICAL RELEVANCE There was a high frequency of the FASLG variant allele (0.14) in this small sample of BSH cats, with 22% of healthy cats identified as carriers of the FASLG variant. For an inherited disease, lethal at a young age, in a small population in which inbreeding is common, these results are significant. To prevent future cases of disease and stop further spread of the FASLG variant allele within the BSH population in New Zealand, it is recommended that all BSH and BSH-cross cats be tested for the presence of the FASLG variant before mating. Cats identified as carriers of the variant allele should be desexed and not used for breeding. Results support the need for further investigations of the true frequency of the FASLG variant allele and occurrence of FALPS in the wider population of BSH cats in New Zealand.

A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats.

OBJECTIVE: Scottish fold cats, named for their unique ear shape, have a dominantly inherited osteochondrodysplasia involving malformation in the distal forelimbs, distal hindlimbs and tail, and progressive joint destruction. This study aimed to identify the gene and the underlying variant responsible for the osteochondrodysplasia. DESIGN: DNA samples from 44 Scottish fold and 54 control cats were genotyped using a feline DNA array and a case-control genome-wide association analysis conducted. The gene encoding a calcium permeable ion channel, transient receptor potential cation channel, subfamily V, member 4 (TRPV4) was identified as a candidate within the associated region and sequenced. Stably transfected HEK293 cells were used to compare wild-type and mutant TRPV4 expression, cell surface localisation and responses to activation with a synthetic agonist GSK1016709A, hypo-osmolarity, and protease-activated receptor 2 stimulation. RESULTS: The dominantly inherited folded ear and osteochondrodysplasia in Scottish fold cats is associated with a p.V342F substitution (c.1024G>T) in TRPV4. The change was not found in 648 unaffected cats. Functional analysis in HEK293 cells showed V342F mutant TRPV4 was poorly expressed at the cell surface compared to wild-type TRPV4 and as a consequence the maximum response to a synthetic agonist was reduced. Mutant TRPV4 channels had a higher basal activity and an increased response to hypotonic conditions. CONCLUSIONS: Access to a naturally-occurring TRPV4 mutation in the Scottish fold cat will allow further functional studies to identify how and why the mutations affect cartilage and bone development.

Toward a genome-wide approach for detecting hybrids: informative SNPs to detect introgression between domestic cats and European wildcats (Felis silvestris).

Endemic gene pools have been severely endangered by human-mediated hybridization, which is posing new challenges in the conservation of several vertebrate species. The endangered European wildcat is an example of this problem, as several natural populations are suffering introgression of genes from the domestic cat. The implementation of molecular methods for detecting hybridization is crucial for supporting appropriate conservation programs on the wildcat. In this study, genetic variation at 158 single-nucleotide polymorphisms (SNPs) was analyzed in 139 domestic cats, 130 putative European wildcats and 5 captive-bred hybrids (N=274). These SNPs were variable both in wild (HE=0.107) and domestic cats (HE=0.340). Although we did not find any SNP that was private in any population, 22 SNPs were monomorphic in wildcats and pairwise FCT values revealed marked differences between domestic and wildcats, with the most divergent 35 loci providing an average FCT>0.74. The power of all the loci to accurately identify admixture events and discriminate the different hybrid categories was evaluated. Results from simulated and real genotypes show that the 158 SNPs provide successful estimates of admixture, with 100% hybrid individuals (two to three generations in the past) being correctly identified in STRUCTURE and over 92% using the NEWHYBRIDS' algorithm. None of the unclassified cats were wrongly allocated to another hybrid class. Thirty-five SNPs, showing the highest FCT values, provided the most parsimonious panel for robust inferences of parental and first generations of admixed ancestries. This approach may be used to further reconstruct the evolution of wildcat populations and, hopefully, to develop sound conservation guidelines for its legal protection in Europe.

Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed.

Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2-bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty-seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4. Fifty-six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A(P) (be) ) and domestic cat non-agouti (a) haplotypes. Twenty-four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non-agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats.

Variation of cats under domestication: genetic assignment of domestic cats to breeds and worldwide random-bred populations.

Both cat breeders and the lay public have interests in the origins of their pets, not only in the genetic identity of the purebred individuals, but also in the historical origins of common household cats. The cat fancy is a relatively new institution with over 85% of its 40-50 breeds arising only in the past 75 years, primarily through selection on single-gene aesthetic traits. The short, yet intense cat breed history poses a significant challenge to the development of a genetic marker-based breed identification strategy. Using different breed assignment strategies and methods, 477 cats representing 29 fancy breeds were analysed with 38 short tandem repeats, 148 intergenic and five phenotypic single nucleotide polymorphisms. Results suggest the frequentist method of Paetkau (single nucleotide polymorphisms = 0.78, short tandem repeats = 0.88) surpasses the Bayesian method of Rannala and Mountain (single nucleotide polymorphisms = 0.56, short tandem repeats = 0.83) for accurate assignment of individuals to the correct breed. Additionally, a post-assignment verification step with the five phenotypic single nucleotide polymorphisms accurately identified between 0.31 and 0.58 of the misassigned individuals raising the sensitivity of assignment with the frequentist method to 0.89 and 0.92 for single nucleotide polymorphisms and short tandem repeats respectively. This study provides a novel multistep assignment strategy and suggests that, despite their short breed history and breed family groupings, a majority of cats can be assigned to their proper breed or population of origin, that is, race.

Anchored reference loci for comparative genome mapping in mammals.

Recent advances in gene mapping technologies have led to increased emphasis in developing representative genetic maps for several species, particularly domestic plants and animals. These maps are being compiled with two distinct goals: to provide a resource for genetic analysis, and to help dissect the evolution of genome organization by comparing linkage relationships of homologous genes. We propose here a list of 321 reference anchor loci suitable for comparative gene mapping in mammals and other vertebrate classes. We selected cloned mouse and human functional genes spaced an average of 5-10 centiMorgans throughout their respective genomes. We also attempted to include loci that are evolutionarily conserved and represented in comparative gene maps in other mammalian orders, particularly cattle and the domestic cat. We believe that the map may provide the basis for a unified approach to comparative analysis of mammalian species genomes.

Comparative anchor tagged sequences (CATS) for integrative mapping of mammalian genomes.

Precise comparisons of mammalian gene maps require common anchor loci as landmarks for conserved chromosomal segments. Using a computer script that automates DNA sequence database alignments, we designed 410 evolutionarily conserved primer pair sequences which are specific for anchor locus gene amplification from any mammalian species' DNA. Primer pairs were designed to span introns for polymorphism ascertainment, and to include sufficient exonic sequence (25-400 bp) to allow for gene identification. A total of 318 primer pairs were optimized for domestic cats, and 86% of the sequenced feline PCR products showed homology to the gene of primer origin. A screen of 20 mammals from 11 orders revealed that 35-52% of the 318 primers yielded a single PCR product without further optimization suggesting that nearly 75% can be optimized for any eutherian mammal.

A high-resolution 15,000(Rad) radiation hybrid panel for the domestic cat.

The current genetic and recombination maps of the cat have fewer than 3,000 markers and a resolution limit greater than 1 Mb. To complement the first-generation domestic cat maps, support higher resolution mapping studies, and aid genome assembly in specific areas as well as in the whole genome, a 15,000(Rad) radiation hybrid (RH) panel for the domestic cat was generated. Fibroblasts from the female Abyssinian cat that was used to generate the cat genomic sequence were fused to a Chinese hamster cell line (A23), producing 150 hybrid lines. The clones were initially characterized using 39 short tandem repeats (STRs) and 1,536 SNP markers. The utility of whole-genome amplification in preserving and extending RH panel DNA was also tested using 10 STR markers; no significant difference in retention was observed. The resolution of the 15,000(Rad) RH panel was established by constructing framework maps across 10 different 1-Mb regions on different feline chromosomes. In these regions, 2-point analysis was used to estimate RH distances, which compared favorably with the estimation of physical distances. The study demonstrates that the 15,000(Rad) RH panel constitutes a powerful tool for constructing high-resolution maps, having an average resolution of 40.1 kb per marker across the ten 1-Mb regions. In addition, the RH panel will complement existing genomic resources for the domestic cat, aid in the accurate re-assemblies of the forthcoming cat genomic sequence, and support cross-species genomic comparisons.

Comparative fertility of freshly collected vs frozen-thawed semen with laparoscopic oviductal artificial insemination in domestic cats.

Artificial insemination (AI) is potentially invaluable as an adjunct to natural breeding for the conservation management of non-domestic felid populations. The efficacy of AI, however, must be substantially improved for applied use, especially when using frozen semen. Our recent advances in using laparoscopic oviductal AI (LO-AI) with low sperm numbers and freezing of cat semen in a soy lecithin-based cryoprotectant medium suggest that combining these two approaches might improve pregnancy outcomes with frozen-thawed spermatozoa. In this study, our objectives were to (i) assess the effect of two gonadotropin dosages (100 vs 150 IU eCG) on ovarian response in domestic cats and (ii) compare the relative fertility of frozen-thawed and fresh semen in vivo following LO-AI. All 16 females ovulated after gonadotropin treatment and were inseminated with fresh semen from one male and frozen-thawed semen from a second male. There were no differences between gonadotropin dosages in CL number, pregnancy percentage or litter size. Half (8/16) of the females conceived, with seven females giving birth to a total of 36 offspring. Paternity analysis showed that more kittens resulted from LO-AI with fresh (28/36, 78%) than frozen-thawed (8/36, 22%) semen, possibly due to impaired motility and longevity of thawed sperm. These results demonstrated that viable offspring can be produced by AI using semen frozen in a soy lecithin-based medium. Insemination with greater numbers of frozen-thawed spermatozoa, combined with further refinement of cat sperm cryopreservation methods, may be necessary to optimize pregnancy success with LO-AI in domestic and nondomestic cats.

A case of SRY-positive 38,XY true hermaphroditism (XY sex reversal) in a cat.

Investigation of abnormal sexual development in companion animals can allow for the elimination of inherited disorders from breeding populations while contributing to the understanding of the complex process of mammalian sexual development and differentiation. A 1-year-old mixed-breed cat, presented for neutering, was tentatively diagnosed as a male with bilateral cryptorchidism. During surgery, the surgeon identified gonads in an ovarian position and a complete bicornuate uterus. Both testicular and ovarian architecture in the gonads and Mullerian and Wolffian duct derivatives were identified histologically. The karyotype was that of a normal male (38,XY), and no causative mutation was identified in the feline SRY coding sequence amplified from genomic DNA. All features of the case were compatible with a diagnosis of SRY-positive 38,XY sex reversal, true hermaphrodite phenotype. To the authors' knowledge, this is the first report of this disorder in a domestic cat.

Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST.

Chediak-Higashi Syndrome (CHS) is a well-characterized, autosomal recessively inherited lysosomal disease caused by mutations in lysosomal trafficking regulator (LYST). The feline model for CHS was originally maintained for ~20 years. However, the colonies were disbanded and the CHS cat model was lost to the research community before the causative mutation was identified. To resurrect the cat model, semen was collected and cryopreserved from a lone, fertile,  CHS carrier male. Using cryopreserved semen, laparoscopic oviductal artificial insemination was performed on three queens, two queens produced 11 viable kittens. To identify the causative mutation, a fibroblast cell line, derived from an affected cat from the original colony, was whole genome sequenced. Visual inspection of the sequence data identified a candidate causal variant as a ~20 kb tandem duplication within LYST, spanning exons 30 through to 38 (NM_001290242.1:c.8347-2422_9548 + 1749dup). PCR genotyping of the produced offspring demonstrated three individuals inherited the mutant allele from the CHS carrier male. This study demonstrated the successful use of cryopreservation and assisted reproduction to maintain and resurrect biomedical models and has defined the variant causing Chediak-Higashi syndrome in the domestic cat.

Resources for genetic management and genomics research on non-human primates at the National Primate Research Centers (NPRCs).

The National Primate Research Centers (NPRCs) established Working Groups (WGs) for developing resources and mechanisms to facilitate collaborations among non-human primate (NHP) researchers. Here we report the progress of the Genome Banking and the Genetics and Genomics WGs in developing resources to advance the exchange, analysis and comparison of NHP genetic and genomic data across the NPRCs. The Genome Banking WG has established a National NHP DNA bank comprising 1250 DNA samples from unrelated animals and family trios from the 10 NHP species housed within the NPRC system. The Genetics and Genomics WG is developing SNP arrays that will provide a uniform, highly informative, efficient and low-cost method for rhesus and long-tailed macaque genotyping across the eight NPRCs. This WG is also establishing a Biomedical Informatics Research Network-based portal for shared bioinformatics resources including vital statistics, genotype and population data and information on the National NHP DNA bank.

A 4,103 marker integrated physical and comparative map of the horse genome.

A comprehensive second-generation whole genome radiation hybrid (RH II), cytogenetic and comparative map of the horse genome (2n = 64) has been developed using the 5000rad horse x hamster radiation hybrid panel and fluorescence in situ hybridization (FISH). The map contains 4,103 markers (3,816 RH; 1,144 FISH) assigned to all 31 pairs of autosomes and the X chromosome. The RH maps of individual chromosomes are anchored and oriented using 857 cytogenetic markers. The overall resolution of the map is one marker per 775 kilobase pairs (kb), which represents a more than five-fold improvement over the first-generation map. The RH II incorporates 920 markers shared jointly with the two recently reported meiotic maps. Consequently the two maps were aligned with the RH II maps of individual autosomes and the X chromosome. Additionally, a comparative map of the horse genome was generated by connecting 1,904 loci on the horse map with genome sequences available for eight diverse vertebrates to highlight regions of evolutionarily conserved syntenies, linkages, and chromosomal breakpoints. The integrated map thus obtained presents the most comprehensive information on the physical and comparative organization of the equine genome and will assist future assemblies of whole genome BAC fingerprint maps and the genome sequence. It will also serve as a tool to identify genes governing health, disease and performance traits in horses and assist us in understanding the evolution of the equine genome in relation to other species.

Comparative genomics: lessons from cats.

The genomics era, spear headed by dazzling technological developments in human and mouse gene mapping, has additionally provoked extensive comparative gene mapping projects for domestic species of several vertebrate orders. As the human genome project promises a one dimensional string of 100,000 genes and sequences, comparative mapping will extend that inference to a second dimension representing index species of the 20 living mammalian orders and to a third dimension by phylogenetic description of the genomes of mammal ancestors. We review here the remarkable extent of genome homology conservation among mammals illustrated by technology applications in the feline genome project.