Extensive genome-wide linkage disequilibrium in cattle.

A genome-wide linkage disequilibrium (LD) map was generated using microsatellite genotypes (284 autosomal microsatellite loci) of 581 gametes sampled from the dutch black-and-white dairy cattle population. LD was measured between all marker pairs, both syntenic and nonsyntenic. Analysis of syntenic pairs revealed surprisingly high levels of LD that, although more pronounced for closely linked marker pairs, extended over several tens of centimorgan. In addition, significant gametic associations were also shown to be very common between nonsyntenic loci. Simulations using the known genealogies of the studied sample indicate that random drift alone is likely to account for most of the observed disequilibrium. No clear evidence was obtained for a direct effect of selection ("Bulmer effect"). The observation of long range disequilibrium between syntenic loci using low-density marker maps indicates that LD mapping has the potential to be very effective in livestock populations. The frequent occurrence of gametic associations between nonsyntenic loci, however, encourages the combined use of linkage and linkage disequilibrium methods to avoid false positive results when mapping genes in livestock.

Fine-mapping of quantitative trait loci by identity by descent in outbred populations: application to milk production in dairy cattle.

We previously mapped a quantitative trait locus (QTL) affecting milk production to bovine chromosome 14. To refine the map position of this QTL, we have increased the density of the genetic map of BTA14q11-16 by addition of nine microsatellites and three single nucleotide polymorphisms. Fine-mapping of the QTL was accomplished by a two-tiered approach. In the first phase, we identified seven sires heterozygous "Qq" for the QTL by marker-assisted segregation analysis in a Holstein-Friesian pedigree comprising 1,158 individuals. In a second phase, we genotyped the seven selected sires for the newly developed high-density marker map and searched for a shared haplotype flanking an hypothetical, identical-by-descent QTL allele with large substitution effect. The seven chromosomes increasing milk fat percentage were indeed shown to carry a common chromosome segment with an estimated size of 5 cM predicted to contain the studied QTL. The same haplotype was shown to be associated with increased fat percentage in the general population as well, providing additional support in favor of the location of the QTL within the corresponding interval.

A QTL affecting milk yield and composition maps to bovine chromosome 20: a confirmation.

As part of a whole genome scan undertaken to detect quantitative trait loci (QTL) affecting milk yield and composition, we have genotyped a granddaughter design comprising 1152 sons for six microsatellite markers spanning bovine chromosome 20. An analysis performed across families provided strong evidence (experiment-wise P-values < 0.01) for the presence of a QTL affecting primarily protein percentage towards the telomeric end of the chromosome. A founder sire, shown in a previous study to segregate for a similar QTL in the corresponding chromosome region, was characterized by 29 and 57 sons and maternal grandsons, respectively, in the present design. Sorting corresponding sons and grandsons by paternal or grandpaternal allele provided significant evidence for the segregation of a QTL on chromosome 20. Altogether these results confirm the location of a QTL affecting milk production on bovine chromosome 20.

A QTL with major effect on milk yield and composition maps to bovine chromosome 14.

A whole genome scan was undertaken in a granddaughter design comprising 1158 progeny-tested bulls in order to map QTL influencing milk yield and composition. In this paper we report the identification of a locus on the centromeric end of bovine Chromosome (Chr) 14, with major effect on fat and protein percentage as well as milk yield. The genuine nature of this QTL was verified using the grand2-daughter design, that is, by tracing the segregating QTL alleles from heterozygous grandsires to their maternal grandsons and confirming the predicted QTL allele substitution effect.

Identity-by-descent mapping of recessive traits in livestock: application to map the bovine syndactyly locus to chromosome 15.

Twelve animals affected with syndactyly or mulefoot were sampled in the Dutch black-and-white cattle population. Analysis of the pedigree data reveal that all of these individuals traced back to a single acknowledged carrier founder individual. Between seven and nine generations separated the founder from its 12 affected descendents. The 12 affected offspring were genotyped for a battery of 213 microsatellites spanning the 29 bovine autosomes. The resulting genotypes were analyzed using a maximum likelihood approach searching for shared homozygous haplotypes among affected individuals. Three candidate regions for the syndactyly locus emerged from this initial screening. syndactyly was shown to map to one of these candidate regions on chromosome 15 by genotyping 29 additional individuals linking founder and affected offspring and performing a conventional linkage analysis with the LINKAGE programs. This study illustrates the potential of identity-by-descent mapping in livestock populations.

The mh gene causing double-muscling in cattle maps to bovine Chromosome 2.

While the hereditary nature of the "double-muscling" phenotype (a generalized muscular hypertrophy documented in several cattle breeds) is well established, its precise segregation mode has remained controversial. Both monogenic models (autosomal dominant or recessive) and oligogenic models have been proposed. Using a panel of 213 bovine microsatellite markers, and an experimental pedigree obtained by backing "double-muscled (Belgian Blue) x conventional (Friesian)"1 dams to double-muscle sire, we have mapped a locus on bovine Chromosome (CHr) 2 that accounts for all the phenotypic variance in the backcross generation. This locus, referred to as mh (muscular hypertrophy), has been positioned with respects to a map composed of seven Chr 2-specific microsatellites, at 2 cM from the closet marker. This result confirms the validity in the Belgian Blue population of the monogenic model involving an autosomal mh locus, characterized by a wild-type "+" and a recessive "mh" allele, causing the double-muscling phenotype in the homozygous condition. The linkage relationship between the mh locus and the Chr 2 markers was confirmed in three informative pedigrees collected from the general Belgian Blue Cattle population, reinforcing the notice of genetic homogeneity of the double-muscling trait in this breed. This work paves the way towards marker-assisted selection for or against the double muscling trait, and towards positional cloning of the corresponding gene.

Comparison of argyrophilic nucleolar organizer regions by counting and image analysis in canine mammary tumors.

Two techniques for evaluating argyrophilic nucleolar organizer regions (AgNOR) were compared on 74 canine mammary tumors to discriminate between benign and malignant lesions. For each lesion, direct counting of AgNOR on at least 100 cell nuclei was compared with area, perimeter, and integrated optical density AgNOR dot values determined by image analysis. Significant differences between benign and malignant tumors were observed with both methods; however, lesions determined as aggressive or proliferative by histologic evaluation were only singled out by image analysis measurements. Image analysis, in our hands, was a reliable, precise, and convenient technique to characterize malignancy in canine mammary tumors.