Linkage disequilibrium on the bovine X chromosome: Characterization and use in quantitative trait locus mapping

in Genetics (2006), 173(3), 1777-1786

We herein demonstrate that in the Holstein-Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between ... [more ▼]

We herein demonstrate that in the Holstein-Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between these markers is higher on the X chromosome than on the autosomes. The latter observation is not compatible with the small male-to-female ratio that prevails in this population and results in a higher gonosomal than autosomal effective population size. It suggests that the X chromosome undergoes distinct selective or mutational forces. We describe and characterize a novel Markovian approach to exploit this linkage disequilibrium to compute the probability that two chromosomes are identical-by-descent conditional on flanking marker data. We use the ensuing probabilities in a restricted maximum-likelihood approach to search for quantitative trait loci (QTL) affecting 48 traits of importance to the dairy industry and provide evidence for the presence of QTL affecting 5 of these traits on the bovine X chromosome. [less ▲]

Results of a whole-genome quantitative trait locus scan for growth, carcass composition and meat quality in a porcine four-way cross.

in Animal Genetics (2006), 37(6), 543-53

A whole-genome quantitative trait locus (QTL) scan for 31 phenotypes related to growth, carcass composition and meat quality was conducted using 1187 progeny of a commercial four-way cross. Animals were ... [more ▼]

A whole-genome quantitative trait locus (QTL) scan for 31 phenotypes related to growth, carcass composition and meat quality was conducted using 1187 progeny of a commercial four-way cross. Animals were genotyped for 198 microsatellite markers that spanned the entire porcine genome. QTL analysis was conducted to extract information from paternal and maternal meioses separately using a rank-based nonparametric approach for half-sib designs. Nine QTL exceeded genome-wide significance: one QTL affecting growth (average daily gain on SSC1), two QTL influencing carcass composition (fatness on SSC3 and muscle mass on SSC15) and six QTL influencing meat quality (tenderness on SSC4 and SSC14; colour on SSC5, SSC6 and SSCX; and conductivity on SSC16). All but one of these coincided with previously reported QTL. In addition, we present evidence for 78 suggestive QTL with a combined false discovery rate of 40%. [less ▲]

Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition

in Proceedings of the National Academy of Sciences of the United States of America (2004), 101(8), 2398-2403

We recently used a positional cloning approach to identify a nonconservative lysine to alanine substitution (K232A) in the bovine DGAT1 gene that was proposed to be the causative quantitative trait ... [more ▼]

We recently used a positional cloning approach to identify a nonconservative lysine to alanine substitution (K232A) in the bovine DGAT1 gene that was proposed to be the causative quantitative trait nucleotide underlying a quantitative trait locus (QTL) affecting milk fat composition, previously mapped to the centromeric end of bovine chromosome 14. We herein generate genetic and functional data that confirm the causality of the DGAT1 K232A mutation. We have constructed a high-density single-nucleotide polymorphism map of the 3.8-centimorgan BULGE30-BULGE9 interval containing the QTL and show that the association with milk fat percentage maximizes at the DGAT1 gene. We provide evidence that the K allele has undergone a selective sweep. By using a baculovirus expression system, we have expressed both DGAT1 alleles in Sf9 cells and show that the K allele, causing an increase in milk fat percentage in the live animal, is characterized by a higher V-max in producing triglycerides than the A allele. [less ▲]

Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition.

in Genetics (2003), 163(1), 253-66

We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome ... [more ▼]

We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome 20 marker map and by exploiting linkage disequilibrium using two distinct approaches, we provide strong evidence that a chromosome segment including the gene coding for the growth hormone receptor accounts for at least part of the chromosome 20 QTL effect. By sequencing individuals with known QTL genotype, we identify an F to Y substitution in the transmembrane domain of the growth hormone receptor gene that is associated with a strong effect on milk yield and composition in the general population. [less ▲]

Simultaneous mining of linkage and linkage disequilibrium to fine map quantitative trait loci in outbred half-sib pedigrees: Revisiting the location of a quantitative trait locus with major effect on milk production on bovine chromosome 14

in Genetics (2002), 161(1), 275-287

A maximum-likelihood QTL mapping method that simultaneously exploits linkage and linkage disequilibrium and that is applicable in outbred half-sib pedigrees is described. The method is applied to fine map ... [more ▼]

A maximum-likelihood QTL mapping method that simultaneously exploits linkage and linkage disequilibrium and that is applicable in outbred half-sib pedigrees is described. The method is applied to fine map a QTL with major effect on milk fat content in a 3-cM marker interval on proximal BTA14. This proximal location is confirmed by applying a haplotype-based association method referred to as recombinant ancestral haplotype analysis. The origin of the discrepancy between the QTL position derived in this work and that of a previous analysis is examined and shown to be due to the existence of distinct marker haplotypes associated with QTL alleles having large substitution effects. [less ▲]

Convenient Genotyping of Six Myostatin Mutations Causing Double-Muscling in Cattle Using a Multiplex Oligonucleotide Ligation Assay

in Animal Genetics (2000), 31(6), 396-9

We herein describe a procedure that allows for simultaneous genotyping of six loss-of-function mutations in the bovine myostatin gene associated with the double-muscling phenotype. The proposed method ... [more ▼]

We herein describe a procedure that allows for simultaneous genotyping of six loss-of-function mutations in the bovine myostatin gene associated with the double-muscling phenotype. The proposed method relies on a multiplex oligonucleotide ligation assay and detection of the fluorescently labelled products using automatic sequencers. [less ▲]

Fine-Mapping of Quantitative Trait Loci by Identity by Descent in Outbred Populations: Application to Milk Production in Dairy Cattle

in Proceedings of the National Academy of Sciences of the United States of America (1999), 96(16), 9252-9257

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 ... [more ▼]

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. [less ▲]

The great-grand-daughter design: a simple strategy to increase the power of a grand-daughter design for QTL mapping

in Genetical Research (1999), 74

A Rank-Based Nonparametric Method for Mapping Quantitative Trait Loci in Outbred Half-Sib Pedigrees: Application to Milk Production in a Granddaughter Design

in Genetics (1998), 149(3), 1547-55

We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated ... [more ▼]

We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated on a simulated dataset and its efficiency compared with interval mapping by using regression. It was shown that the rank-based approach is slightly inferior to regression when the residual variance is homoscedastic normal; however, in three out of four other scenarios envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed, and homoscedastic positively kurtosed, the latter outperforms the former one. Both methods were applied to a real data set analyzing the effect of bovine chromosome 6 on milk yield and composition by using a 125-cM map comprising 15 microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires. [less ▲]

A Qtl with Major Effect on Milk Yield and Composition Maps to Bovine Chromosome 14

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (1998), 9(7), 540-4

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 ... [more ▼]

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. [less ▲]