12 research outputs found
The Contribution of Copy Number Variants and Single Nucleotide Polymorphisms to the Additive Genetic Variance of Carcass Traits in Cattle
The relative contributions of both copy number variants (CNVs) and single nucleotide polymorphisms (SNPs) to the additive genetic variance of carcass traits in cattle is not well understood. A detailed understanding of the relative importance of CNVs in cattle may have implications for study design of both genomic predictions and genome-wide
association studies. The first objective of the present study was to quantify the relative contributions of CNV data and SNP genotype data to the additive genetic variance of
carcass weight, fat, and conformation for 945 Charolais, 923 Holstein-Friesian, and 974 Limousin sires. The second objective was to jointly consider SNP and CNV data in a least absolute selection and shrinkage operator (LASSO) regression model to identify genomic regions associated with carcass weight, fat, and conformation within each of the three breeds separately. A genomic relationship matrix (GRM) based on just CNV data did not capture any variance in the three carcass traits when jointly evaluated with a SNP-derived GRM. In the LASSO regression analysis, a total of 987 SNPs and 18 CNVs were associated with at least one of the three carcass traits in at least one of the three
breeds. The quantitative trait loci (QTLs) corresponding to the associated SNPs and CNVs overlapped with several candidate genes including previously reported candidate
genes such as MSTN and RSAD2, and several potential novel candidate genes such as ACTN2 and THOC1. The results of the LASSO regression analysis demonstrated that CNVs can be used to detect associations with carcass traits which were not detected using the set of SNPs available in the present study. Therefore, the CNVs and SNPs available in the present study were not redundant forms of genomic data
Concordance rate between copy number variants detected using either high- or medium-density single nucleotide polymorphism genotype panels and the potential of imputing copy number variants from flanking high density single nucleotide polymorphism haplotypes in cattle
peer-reviewedBackground
The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number.
Results
For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed.
Conclusion
The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel
Is the observed high-frequency radio luminosity distribution of QSOs bimodal?
The distribution of QSO radio luminosities has long been debated in the
literature. Some argue that it is a bimodal distribution, implying that there
are two separate QSO populations (normally referred to as 'radio-loud' and
'radio-quiet'), while others claim it forms a more continuous distribution
characteristic of a single population. We use deep observations at 20 GHz to
investigate whether the distribution is bimodal at high radio frequencies.
Carrying out this study at high radio frequencies has an advantage over
previous studies as the radio emission comes predominantly from the core of the
AGN, hence probes the most recent activity. Studies carried out at lower
frequencies are dominated by the large scale lobes where the emission is built
up over longer timescales (10^7-10^8 yrs), thereby confusing the sample. Our
sample comprises 874 X-ray selected QSOs that were observed as part of the 6dF
Galaxy Survey. Of these, 40% were detected down to a 3 sigma detection limit of
0.2-0.5 mJy.
No evidence of bimodality is seen in either the 20 GHz luminosity
distribution or in the distribution of the R_20 parameter: the ratio of the
radio to optical luminosities traditionally used to classify objects as being
either radio-loud or radio-quiet. Previous results have claimed that at low
radio luminosities, star formation processes can dominate the radio emission
observed in QSOs. We attempt to investigate these claims by stacking the
undetected sources at 20 GHz and discuss the limitations in carrying out this
analysis. However, if the radio emission was solely due to star formation
processes, we calculate that this corresponds to star formation rates ranging
from ~10 solar masses/yr to ~2300 solar masses/yr.Comment: 13 pages, 11 figures. Accepted for publication in Ap
Genome-wide association analyses of carcass traits using copy number variants and raw intensity values of single nucleotide polymorphisms in cattle
peer-reviewedBackground
The carcass value of cattle is a function of carcass weight and quality. Given the economic importance of carcass merit to producers, it is routinely included in beef breeding objectives. A detailed understanding of the genetic variants that contribute to carcass merit is useful to maximize the efficiency of breeding for improved carcass merit. The objectives of the present study were two-fold: firstly, to perform genome-wide association analyses of carcass weight, carcass conformation, and carcass fat using copy number variant (CNV) data in a population of 923 Holstein-Friesian, 945 Charolais, and 974 Limousin bulls; and secondly to perform separate association analyses of carcass traits on the same population of cattle using the Log R ratio (LRR) values of 712,555 single nucleotide polymorphisms (SNPs). The LRR value of a SNP is a measure of the signal intensity of the SNP generated during the genotyping process.
Results
A total of 13,969, 3,954, and 2,805 detected CNVs were tested for association with the three carcass traits for the Holstein-Friesian, Charolais, and Limousin, respectively. The copy number of 16 CNVs and the LRR of 34 SNPs were associated with at least one of the three carcass traits in at least one of the three cattle breeds. With the exception of three SNPs, none of the quantitative trait loci detected in the CNV association analyses or the SNP LRR association analyses were also detected using traditional association analyses based on SNP allele counts. Many of the CNVs and SNPs associated with the carcass traits were located near genes related to the structure and function of the spliceosome and the ribosome; in particular, U6 which encodes a spliceosomal subunit and 5S rRNA which encodes a ribosomal subunit.
Conclusions
The present study demonstrates that CNV data and SNP LRR data can be used to detect genomic regions associated with carcass traits in cattle providing information on quantitative trait loci over and above those detected using just SNP allele counts, as is the approach typically employed in genome-wide association analyses
Characterization of copy number variants in a large multibreed population of beef and dairy cattle using high-density single nucleotide polymorphism genotype data
Copy number variants (CNVs)
are a form of genomic variation that changes
the structure of the genome through deletion or
duplication of stretches of DNA. The objective
of the present study was to characterize CNVs in
a large multibreed population of beef and dairy
bulls. The CNVs were called on the autosomes
of 5,551 cattle from 22 different beef and dairy
breeds, using 2 freely available software suites,
QuantiSNP and PennCNV. All CNVs were classified into either deletions or duplications. The
median concordance between PennCNV and
QuantiSNP, per animal, was 18.5% for deletions
and 0% for duplications. The low concordance
rate between PennCNV and QuantiSNP indicated
that neither algorithm, by itself, could identify
all CNVs in the population. In total, PennCNV
and QuantiSNP collectively identified 747,129
deletions and 432,523 duplications; 80.2% of all
duplications and 69.1% of all deletions were present only once in the population. Only 0.154% of
all CNVs identified were present in more than 50
animals in the population. The distribution of the
percentage of the autosomes that were composed
of deletions, per animal, was positively skewed,
as was the distribution for the percentage of the
autosomes that were composed of duplications,
per animal. The first quartile, median, and third
quartile of the distribution of the percentage of
the autosomes that were composed of deletions
were 0.019%, 0.037%, and 0.201%, respectively.
The first quartile, median, and third quartile of the
distribution of the percentage of the autosomes
that were composed of duplications were 0.013%,
0.028%, and 0.076%, respectively. The distributions of the number of deletions and duplications
per animal were both positively skewed. The interquartile range for the number of deletions per animal in the population was between 16 and 117,
whereas for duplications it was between 8 and
23. Per animal, there tended to be twice as many
deletions as duplications. The distribution of the
length of deletions was positively skewed, as was
the distribution of the length of duplications. The
interquartile range for the length of deletions in
the population was between 25 and 101 kb, and for
duplications the interquartile range was between
46 and 235 kb. Per animal, duplications tended to
be twice as long as deletions. This study provides a
description of the characteristics and distribution
of CNVs in a large multibreed population of beef
and dairy cattle
Variation in the proportion of the segregating genome shared between full-sibling cattle and sheep
Abstract The construction of covariance matrices that account for the genetic relationships among individuals, using pedigree or genotype data, is integral to genetic evaluations, which are now routinely used in the field of animal breeding. The objective of the present study was to estimate the standard deviation in the proportion of the segregating genome that is shared between pairs of full-sibling cattle and sheep independently. Post edits, genotype data comprising 46,069 autosomal single nucleotide polymorphisms (SNPs) were available for 4532 unique full-sibling sheep pairs, as well as for their respective parents. Post edits, genotypes from 50,493 autosomal SNPs were also available for 10,000 unique full-sibling cattle pairs, as well as their respective parents. Genomic relationship matrices were constructed for the sheep and cattle populations, separately. After accounting for both parental genomic inbreeding and the genomic relationship between both parents, the standard deviation in full-sibling cattle and sheep genomic relationships was 0.040 and 0.037 units, respectively. In addition, the intercept value from a linear regression model which regressed each full-sibling genomic relationship on both sire and dam inbreeding, as well as the genomic relationship between the parents, was 0.499 (0.001) for sheep and 0.500 (0.001) for cattle, conforming to the expectation that full-siblings, on average, share 50% of their segregating genome
Additional file 1 of Variation in the proportion of the segregating genome shared between full-sibling cattle and sheep
Additional file 1: Figure S1. Quantile–quantile plots of the model residuals from the models used to adjust the genomic relationships between full-sibling cattle (a) and sheep (b) pairs. Figure S2. Scatter plot of the top four principal components of the genomic relationship matrix (GRM) for the full-sibling sheep population. Crossbred sheep are represented by brown dots, Belclare are in blue, Suffolk are in yellow, Texel are in purple, and Vendeen are in green
Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat
The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. Surprisingly, data from the longest-living rodent known, naked mole-rats [MRs; mass 35 g; maximum lifespan (MLSP) > 28.3 years], when compared with mice (MLSP 3.5 years) exhibit higher levels of lipid peroxidation, protein carbonylation, and DNA oxidative damage even at a young age. We hypothesize that age-related changes in protein structural stability, oxidation, and degradation are abrogated over the lifespan of the MR. We performed a comprehensive study of oxidation states of protein cysteines [both reversible (sulfenic, disulfide) and indirectly irreversible (sulfinic/sulfonic acids)] in liver from young and old C57BL/6 mice (6 and 28 months) and MRs (2 and >24 years). Furthermore, we compared interspecific differences in urea-induced protein unfolding and ubiquitination and proteasomal activity. Compared with data from young mice, young MRs have 1.6 times as much free protein thiol groups and similar amounts of reversible oxidative damage to cysteine. In addition, they show less urea-induced protein unfolding, less protein ubiquitination, and higher proteasome activity. Mice show a significant age-related increase in cysteine oxidation and higher levels of ubiquitination. In contrast, none of these parameters were significantly altered over 2 decades in MRs. Clearly MRs have markedly attenuated age-related accrual of oxidation damage to thiol groups and age-associated up-regulation of homeostatic proteolytic activity. These pivotal mechanistic interspecies differences may contribute to the divergent aging profiles and strongly implicate maintenance of protein stability and integrity in successful aging