Chromosome-wise Threshold Research Articles

A genome-wide association study reveals candidate genes for the supernumerary nipple phenotype in sheep (Ovis aries).

Genome-wide association studies (GWASs) have been widely applied in livestock to identify genes associated with traits of economic interest. Here, we conducted the first GWAS of the supernumerary nipple phenotype in Wadi sheep, a native Chinese sheep breed, based on Ovine Infinium HD SNP BeadChip genotypes in a total of 144 ewes (75 cases with four teats, including two normal and two supernumerary teats, and 69 control cases with two teats). We detected 63 significant SNPs at the chromosome-wise threshold. Additionally, one candidate region (chr1: 170.723-170.734Mb) was identified by haplotype-based association tests, with one SNP (rs413490006) surrounding functional genes BBX and CD47 on chromosome 1 being commonly identified as significant by the two mentioned analyses. Moreover, Gene Ontology enrichment for the significant SNPs identified by the GWAS analysis was functionally clustered into the categories of receptor activity and synaptic membrane. In addition, pathway mapping revealed four promising pathways (Wnt, oxytocin, MAPK and axon guidance) involved in the development of the supernumerary nipple phenotype. Our results provide novel and important insights into the genetic mechanisms underlying the phenotype of supernumerary nipples in mammals, including humans. These findings may be useful for future breeding and genetics in sheep and other livestock.

Genomic breeding value prediction and QTL mapping of QTLMAS2010 data using Bayesian Methods

BackgroundBayesian methods allow prediction of genomic breeding values (GEBVs) using high-density single nucleotide polymorphisms (SNPs) covering the whole genome with effective shrinkage of SNP effects using appropriate priors. In this study we applied a modification of the well-known BayesA and BayesB methods to estimate the proportion of SNPs with zero effects (π) and a common variance for non-zero effects. The method, termed BayesCπ, was used to predict the GEBVs of the last generation of the QTLMAS2010 data. The accuracy of GEBVs from various methods was estimated by the correlation with phenotypes in the last generation. The methods were BayesCPi and BayesB with different π values, both with and without polygenic effects, and best linear unbiased prediction using an animal model with a genomic or numerator relationship matrix. Positions of quantitative trait loci (QTLs) were identified based on the variances of GEBVs for windows of 10 consecutive SNPs. We also proposed a novel approach to set significance thresholds for claiming QTL in this specific case by using pedigree-based simulation of genotypes. All analyses were focused on detecting and evaluating QTL with additive effects.ResultsThe accuracy of GEBVs was highest for BayesCπ, but the accuracy of BayesB with π equal to 0.99 was similar to that of BayesCπ. The accuracy of BayesB dropped with a decrease in π. Including polygenic effects into the model only had marginal effects on accuracy and bias of predictions. The number of QTL identified was 15 when based on a stringent 10% chromosome-wise threshold and increased to 21 when a 20% chromosome-wise threshold was used.ConclusionsThe BayesCπ method without polygenic effects was identified to be the best method for the QTLMAS2010 dataset, because it had highest accuracy and least bias. The significance criterion based on variance of 10-SNP windows allowed detection of more than half of the QTL, with few false positives.

A quantitative trait locus for faecal worm egg and blood eosinophil counts on chromosome 23 in Australian goats

Three microsatellite markers on goat chromosome 23 adjacent to the MHC were used to test for quantitative trait loci (QTL) affecting faecal worm egg count (WEC) and leukocyte traits in ten Australian Angora and twelve Australian Cashmere half-sib families (n = 16-57 per family). Data were collected from 280 Angora and 347 Cashmere kids over a 3- and 4-year period. A putative QTL affecting trichostrongyle WEC was found in two small families at the 5% chromosome-wise threshold level. The biggest QTL effect for WEC of 1.65 standard deviations (sigma(p)) was found within the region of OarCP73-BM1258. A significant QTL affecting blood eosinophil counts at the 1% chromosome-wise threshold level was detected at marker BM1258 (at 26 cM) in two Angora and Cashmere families. The magnitude of the putative QTL was 0.69 and 0.85 sigma(p) in Angora and Cashmere families, respectively. Due to the comparatively low power of the study these findings should be viewed as indicative rather than definitive.

Fine mapping quantitative trait loci for feed intake and feed efficiency in beef cattle1

Feed intake and feed efficiency are economically important traits in beef cattle because feed is the greatest variable cost in production. Feed efficiency can be measured as feed conversion ratio (FCR, intake per unit gain) or residual feed intake (RFI, measured as DMI corrected for BW and growth rate, and sometimes a measure of body composition, usually carcass fatness, RFI(bf)). The goal of this study was to fine map QTL for these traits in beef cattle using 2,194 markers on 24 autosomes. The animals used were from 20 half-sib families originating from Angus, Charolais, and University of Alberta Hybrid bulls. A mixed model with random sire and fixed QTL effect nested within sire was used to test each location (cM) along the chromosomes. Threshold levels were determined at the chromosome and genome levels using 20,000 permutations. In total, 4 QTL exceeded the genome-wise threshold of P < 0.001, 3 exceeded at P < 0.01, 17 at P < 0.05, and 30 achieved significance at the chromosome-wise threshold level (at least P < 0.05). No QTL were detected on BTA 8, 16, and 27 above the 5% chromosome-wise significance threshold for any of the traits. Nineteen chromosomes contained RFI QTL significant at the chromosome-wise level. The RFI(bf) QTL results were generally similar to those of RFI, the positions being similar, but occasionally differing in the level of significance. Compared with RFI, fewer QTL were detected for both FCR and DMI, 12 and 4 QTL, respectively, at the genome-wise thresholds. Some chromosomes contained FCR QTL, but not RFI QTL, but all DMI QTL were on chromosomes where RFI QTL were detected. The most significant QTL for RFI was located on BTA 3 at 82 cM (P = 7.60 x 10(-5)), for FCR on BTA 24 at 59 cM (P = 0.0002), and for DMI on BTA 7 at 54 cM (P = 1.38 x 10(-5)). The RFI QTL that showed the most consistent results with previous RFI QTL mapping studies were on BTA 1, 7, 18, and 19. The identification of these QTL provides a starting point to identify genes affecting feed intake and efficiency for use in marker-assisted selection and management.

Investigating the genetic component of fatty acid content in sheep milk

The fatty acid (FA) profile of milk fat may affect the nutritional and market value of sheep dairy products. In this study we present repeatability estimates and results of quantitative trait loci (QTL) detection analyses for FA profile of sheep milk obtained by a genome scan approach applied to an experimental Sardinian × Lacaune back-cross population. The experimental flock was constituted by 967 daughters of 10 F1 sires corresponding to a classical daughter design for QTL detection. Fatty acid contents were determined twice in the middle of 2nd (847 records) and 3rd lactation (795 records) by gas chromatography. Means, standard deviations as well as raw correlations were calculated for the 17 most abundant fatty acids, their sums and ratios, based on 1454 records from 727 ewes with two samplings. A repeated measurement model including, as a fixed effect, the year of production by management group interaction and the random effects of sire and animal within sire was applied to all the analysed variables. For each trait R 2 statistics associated with the fixed part of the model, the sire and the animal within sire components of the total variation were estimated. The genotypes at 146 microsatellite markers spanning the 26 ovine autosomes were available. The individual solutions for the 727 ewes with two records were used as phenotypes for QTL analyses. An across-family single trait QTL analysis was carried out by within-family linear regression. Chromosome locations significant at least at the 5% chromosome-wise level were retained. The overall pattern of raw correlations showed that FA profile is a very complex system resulting from numerous inter-relationships between basic FA. The portion of variation absorbed by the fixed part of the model differed markedly across variables, as showed by R 2 statistics which ranged from 11.3% to 78.3%. FA showed large variability in terms of repeatability estimates, which ranged between 14.1% for C18:3 and 57.3% for C4. The most repeatable FA were C4, C14:1 and C17. For almost all the analysed variables, significant genome locations were found. Only for C4 was no genome region affecting the trait variability identified. The highest number of significant locations was found for C14_1 and its ratio with C14. The most significant QTL were detected for C14 and C16 on OAR 11 and for monounsaturated FA (MUFA) on OAR 6. A total of 82 locations significant at least at the 5% chromosome-wise threshold were detected. The present study suggests that for fatty acid profile of sheep milk both classical quantitative genetic approach and genomic information based selection approaches will be realistic options in the future.

Mapping of a Quantitative Trait Locus for Beef Marbling on Bovine Chromosome 9 in Purebred Japanese Black Cattle

The goal of this study is to detect quantitative trait loci (QTL) for carcass traits applicable for a DNA-based breeding system in a Japanese Black cattle population. A purebred paternal half-sib family from a commercial line composed of 65 steers was initially analyzed using 188 informative microsatellites giving a 16-cM average interval covering 29 autosomes. A significant QTL for marbling was detected in the centromeric portion of bovine chromosome (BTA) 9. After additional marker genotyping across a larger sample size composed of 169 individuals, this locus was refined to a 20-cM confidence interval between microsatellites BM1227 (24 cM) and DIK2741 (50 cM) at a 1% chromosome-wise threshold. The allele substitution effect between Q and q for a beef marbling standard score (1 to 12 range) on BTA9 was 1.0 (5.7% of total phenotypic variance in QTL contribution in this family). This result provides a primary platform for a marker-assisted selection system of the beef marbling trait within the Japanese Black (Wagyu) cattle population.

Identification of quantitative trait loci associated with bone traits and body weight in an F2 resource population of chickens*

Bone fractures at the end of lay are a significant problem in egg-laying strains of hens. The objective of the current study was to identify quantitative trait loci (QTL) associated with bone mineralization and strength in a chicken resource population. Layer (White Leghorn hens) and broiler (Cobb-Cobb roosters) lines were crossed to generate an F2 population of 508Â hens over seven hatches, and 26 traits related to bone integrity, including bone mineral density (BMD) and content (BMC), were measured. Genotypes of 120 microsatellite markers on 28 autosomal groups were determined, and interval mapping was conducted to identify QTL regions. Twenty-three tests representing three chromosomal regions (chromosomes 4, 10 and 27) contained significant QTL that surpassed the 5% genome-wise threshold, and 47 tests representing 15 chromosomes identified suggestive QTL that surpassed the 5% chromosome-wise threshold. Although no significant QTL influencing BMD and BMC were detected after adjusting for variation in body weight and egg production, multiple suggestive QTL were found. These results support previous experiments demonstrating an important genetic regulation of bone strength in chickens, but suggest the regulation may be due to the effects of multiple genes that each account for relatively small amounts of variation in bone strength.

Identification of quantitative trait loci associated with bone traits and body weight in an F2 resource population of chickens

Bone fractures at the end of lay are a significant problem in egg-laying strains of hens. The objective of the current study was to identify quantitative trait loci (QTL) associated with bone mineralization and strength in a chicken resource population. Layer (White Leghorn hens) and broiler (Cobb-Cobb roosters) lines were crossed to generate an F2 population of 508Â hens over seven hatches, and 26 traits related to bone integrity, including bone mineral density (BMD) and content (BMC), were measured. Genotypes of 120 microsatellite markers on 28 autosomal groups were determined, and interval mapping was conducted to identify QTL regions. Twenty-three tests representing three chromosomal regions (chromosomes 4, 10 and 27) contained significant QTL that surpassed the 5% genome-wise threshold, and 47 tests representing 15 chromosomes identified suggestive QTL that surpassed the 5% chromosome-wise threshold. Although no significant QTL influencing BMD and BMC were detected after adjusting for variation in body weight and egg production, multiple suggestive QTL were found. These results support previous experiments demonstrating an important genetic regulation of bone strength in chickens, but suggest the regulation may be due to the effects of multiple genes that each account for relatively small amounts of variation in bone strength.

Quantitative Trait Loci Mapping of Functional Traits in the German Holstein Cattle Population

A whole-genome scan to detect quantitative trait loci (QTL) for functional traits was performed in the German Holstein cattle population. For this purpose, 263 genetic markers across all autosomes and the pseudoautosomal region of the sex chromosomes were genotyped in 16 granddaughter-design families with 872 sons. The traits investigated were deregressed breeding values for maternal and direct effects on dystocia (DYSm, DYSd) and stillbirth (STIm, STId) as well as maternal and paternal effects on nonreturn rates of 90 d (NR90m, NR90p). Furthermore, deregressed breeding values for functional herd life (FHL) and daughter yield deviation for somatic cell count (SCC) were investigated. Weighted multimarker regression analyses across families and permutation tests were applied for the detection of QTL and the calculation of statistical significance. A ten percent genomewise significant QTL was localized for DYSm on chromosome 8 and for SCC on chromosome 18. A further 24 putative QTL exceeding the 5% chromosomewise threshold were detected. On chromosomes 7, 8, 10, 18, and X/Yps, coincidence of QTL for several traits was observed. Our results suggest that loci with influence on udder health may also contribute to genetic variance of longevity. Prior to implementation of these QTL in marker assisted selection programs for functional traits, information about direct and correlated effects of these QTL as well as fine mapping of their chromosomal positions is required.