Comparative genomics has its roots in Aristotle, who understood that the commonalities among species would facilitate comprehension of the underlying “differentiae” that distinguish animals with common features. More than 1500 years later, after Mendel expounded the principles of inheritance and Darwin provided the intellectual framework for revealing a common molecular ancestry among species, the first example of linkage conservation in vertebrates was found among mice and rats for the albino coat color allele and pink eye dilution (Feldman 1924). Hence, mammalian form and physiology were understood to have common evolutionary origins arising from chromosome phylogeny. The historical threads to the present detailed gene maps of mammals run through a series of technical breakthroughs, from the use of isozymes, to somatic cell hybrid genetics, to the current explosion in gene mapping brought about by radiation hybrid (RH) technology (Cox et al. 1990). This progress is best represented by > 30,000 mapped human genes (Deloukas et al. 1998) and 2983 mouse–human gene homologies (Mouse Genome Database, Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine; http://www.informatics.jax.org, February, 2000). The development of RH cell panels for a number of species has led to a renaissance in comparative mapping that will soon erase the lead of “model organisms” in genes mapped, thereby revolutionizing our understanding of mammalian chromosome evolution (O'Brien et al. 1999). The phylogenomic approach to studying comparative genome organization and evolution (Eisen 1998; Bouzat et al., 2000) will eventually extend down the Woesian Tree of Life (Woese et al. 1990) until the commonalities among species are reduced to life's essentials and the “differentiae” of earth's biota are understood in molecular terms.

Among mammals, cattle have well-developed synteny and linkage maps (Eggen and Fries 1995; Womack and Kata 1995). There are now nearly 500 structural genes with cattle chromosome assignments (U.S. Bovine ArkDB http://bos.cvm.tamu.edu/bovgbase.html). Most of these genes have been mapped by physical methods, such as somatic cell hybrid analysis and in situ hybridization, leading to the identification of conserved synteny among a diverse spectrum of vertebrate genomes (Wakefield and Graves 1996; O'Brien et al. 1999). Interspecies chromosome painting has been applied to comparative mapping of human and cattle chromosomes (Solinas-Toldo et al. 1995), thus marking the major boundaries of conserved synteny on a genome-wide basis. Although chromosome painting provides a general view of comparative chromosome organization, the ability to draw meaningful inference about chromosomal evolution is limited by a paucity of ordered structural genes on the cattle gene map, i.e., there are < 200 genes on all the published cattle linkage maps (Ma et al. 1996; Barendse et al. 1997; Kappes et al. 1997). Adding genes to an ordered cattle gene map is critically important for the eventual isolation and characterization of genes affecting economically important traits of livestock and for understanding the evolution of vertebrate genomes (Womack and Kata 1995).

Mass production of expressed sequence tags (ESTs) is a powerful method for gene identification (Adams et al. 1991), and the combination of ESTs with RH mapping has proven invaluable for the development of a human gene map (Deloukas et al. 1998). Similarly, the development of a 5000 rad cattle–hamster RH panel opened the door to large-scale gene mapping in cattle (Womack et al. 1997). We recently demonstrated the power of RH mapping of cattle ESTs for comparative genomics (Band et al. 1998; Ma et al. 1998; Ozawa et al. 2000) and have shown that existing knowledge of comparative chromosome organization can be used to predict the map location of ESTs accurately in the cattle genome in silico. This in silico method for comparative genome analysis was termed comparative mapping by annotation and sequence similarity (COMPASS). The COMPASS approach differs from other approaches for comparative mapping, such as comparative anchor tagged sequences (CATS: Lyons et al. 1997), in that COMPASS relies on generating homologous DNA sequence information (e.g., ESTs), followed by similarity search to identify putative orthologs, and then predicting the chromosome location of the sequences on the basis of existing comparative maps. By contrast, CATs utilizes available sequence data. Using the combined approach of COMPASS and RH mapping of ESTs on bovine chromosome 5, we have shown COMPASS to be a useful predictive approach for gene mapping (Ozawa et al. 2000).

Herein, we used ESTs derived from cattle ovary and spleen cDNA libraries and sequences of cattle genes in public domain databases to create a whole-genome RH map. A COMPASS software tool facilitated the map-building process. The whole-genome cattle RH map was anchored with microsatellite markers from the existing cattle linkage maps. Construction of RH maps for all bovine autosomes and the X chromosome allowed us to create detailed cattle–human comparative maps. Our goals were to reveal the spectrum of chromosome rearrangements as compared with the human genome, and to create practical resources for the livestock genomics community. The whole-genome cattle–human comparative map will serve as a cornerstone for efforts to identify genes of agricultural importance and as an essential resource for understanding genome evolution in vertebrates.

/pdf/an-ordered-comparative-map-of-the-cattle-and-human-genomes-349ilskp69.pdf

An ordered comparative map of the cattle and human genomes.

A microsatellite-based high-density genetic map facilitates for fine mapping of hereditary traits of interest, characterization of meiosis, and providing a foundation for physical map construction. Here, we developed a comprehensive genetic map on the basis of >880,000 genotypes across the USDA MARC cattle reference families with a potential genetic resolution of 0.8 cM at the 95% confidence level (∼800 kb in the bovine genome). We incorporated 2325 microsatellites into the second-generation genetic map by linkage analysis based on sex-averaged two-point LOD scores (>3.0), of which 2293 were fine-mapped by multipoint linkage analysis. The new 3160-cM map comprised of 29 sex-averaged autosomal linkage groups and a sex-specific X-chromosome linkage group includes 3960 markers with 2389 positions, resulting in an average interval size of 1.4 cM. More than half (51%) of the total length of the map is covered with intervals of 2.0 cM or less, and the largest gap is a 10.2-cM interval on the X-linkage group. The new map should accelerate fine mapping and positional cloning of genes for genetic diseases and economically important traits in cattle, as well as related livestock species, such as sheep and goat.

/pdf/a-comprehensive-genetic-map-of-the-cattle-genome-based-on-10600tfwdr.pdf

A Comprehensive Genetic Map of the Cattle Genome Based on 3802 Microsatellites

A project of QTL detection was carried out in the French Holstein, Normande, and Montbeliarde dairy cattle breeds. This granddaughter design included 1 548 artificial insemination bulls distributed in 14 sire families and evaluated after a progeny-test for 24 traits (production, milk composition, persistency, type, fertility, mastitis resistance, and milking ease). These bulls were also genotyped for 169 genetic markers, mostly microsatellites. The QTL were analysed by within-sire linear regression of daughter yield deviations or deregressed proofs on the probability that the son receives one or the other paternal QTL allele, given the marker information. QTL were detected for all traits, including those with a low heritability. One hundred and twenty QTL with a chromosome-wise significance lower than 3% were tabulated. This threshold corresponded to a 15% false discovery rate. Amongst them, 32 were genome-wise significant. Estimates of their contribution to genetic variance ranged from 6 to 40%. Most substitution effects ranged from 0.6 to 1.0 genetic standard deviation. For a given QTL, only 1 to 5 families out of 14 were informative. The confidence intervals of the QTL locations were large and always greater than 20 cM. This experiment confirmed several already published QTL but most of them were original, particularly for non-production traits.

/pdf/detection-of-genes-influencing-economic-traits-in-three-30upj1itmj.pdf

Detection of genes influencing economic traits in three french dairy cattle breeds

A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) > or = 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of > 20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of > 1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community.

/pdf/an-enhanced-linkage-map-of-the-sheep-genome-comprising-more-2w3idinz54.pdf

An Enhanced Linkage Map of the Sheep Genome Comprising More Than 1000 Loci

https://aipl.arsusda.gov/publish/jds/2004/87_468.pdf

Detection of quantitative trait loci affecting milk production, health, and reproductive traits in Holstein cattle.

A cattle genetic linkage map was constructed which covers more than 95 percent of the bovine genome at medium density Seven hundred and forty six DNA polymorphisms were genotyped in cattle families which comprise 347 individuals in full sibling pedigrees Seven hundred and three of the loci are linked to at least one other locus All linkage groups are assigned to chromosomes, and all are orientated with regards to the centromere There is little overall difference in the lengths of the bull and cow linkage maps although there are individual differences between maps of chromosomes One hundred and sixty polymorphisms are in or near genes, and the resultant genome-wide comparative analyses indicate that while there is greater conservation of synteny between cattle and humans compared with mice, the conservation of gene order between cattle and humans is much less than would be expected from the conservation of synteny This map provides a basis for high-resolution mapping of the bovine genome with physical resources such as Yeast and Bacterial Artificial Chromosomes as well as providing the underpinning for the interpolation of information from the Human Genome Project

K. Easterday

Papers

A medium density genetic linkage map of the bovine genome