Metagenomic predictions use variation in the metagenome (microbiome profile) to predict the unknown phenotype of the associated host. Metagenomic predictions were first developed 10 years ago, where ...they were used to predict which cattle would produce high or low levels of enteric methane. Since then, the approach has been applied to several traits and species including residual feed intake in cattle, and carcass traits, body mass index and disease state in pigs. Additionally, the method has been extended to include predictions based on other multi-dimensional data such as the metabolome, as well to combine genomic and metagenomic information. While there is still substantial optimisation required, the use of metagenomic predictions is expanding as DNA sequencing costs continue to fall and shows great promise particularly for traits heavily influenced by the microbiome such as feed efficiency and methane emissions.
Continued production of food in areas predicted to be most affected by climate change, such as dairy farming regions of Australia, will be a major challenge in coming decades. Along with rising ...temperatures and water shortages, scarcity of inputs such as high energy feeds is predicted. With the motivation of selecting cattle adapted to these changing environments, we conducted a genome wide association study to detect DNA markers (single nucleotide polymorphisms) associated with the sensitivity of milk production to environmental conditions. To do this we combined historical milk production and weather records with dense marker genotypes on dairy sires with many daughters milking across a wide range of production environments in Australia. Markers associated with sensitivity of milk production to feeding level and sensitivity of milk production to temperature humidity index on chromosome nine and twenty nine respectively were validated in two independent populations, one a different breed of cattle. As the extent of linkage disequilibrium across cattle breeds is limited, the underlying causative mutations have been mapped to a small genomic interval containing two promising candidate genes. The validated marker panels we have reported here will aid selection for high milk production under anticipated climate change scenarios, for example selection of sires whose daughters will be most productive at low levels of feeding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele ...frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Variation in the genome region coding for PLAG1 has well-documented associations with skeletal growth and age at puberty in cattle. However, the influence of PLAG1 on other economically ...important traits such as cow stayability has not yet been explored. Here we investigate the effect of PLAG1 variation on early and later in life female fertility, as well as size and growth, in a well-phenotyped Australian Brahman herd. Yearly pregnancy and productivity records were collected from 2,839 genotyped Brahman cows and used to generate fertility, growth, and weight phenotypes. A variant on chromosome 14 in PLAG1 (NC_037341.1:g.23338890G>T, rs109815800) was previously determined to be a putative causative mutation associated with variation in cattle stature. The imputed PLAG1 genotype at this variant was isolated for each animal and the effect of PLAG1 genotype on each trait was estimated using linear modeling. Regardless of how heifer fertility was measured, there was a significant (P < 0.05) and desirable relationship between the additive effects of PLAG1 genotype and successful heifer fertility. Heifers with two copies of the alternate allele (TT) conceived earlier and had higher pregnancy and calving rates. However, the effects of PLAG1 genotype on fertility began to diminish as cows aged and did not significantly influence stayability at later ages. While there was no effect of genotype on growth, PLAG1 had a negative effect on mature cow weight (P < 0.01), where females with two copies of the alternate allele (TT) were significantly smaller than those with either one or none. Selection emphasis on improved Brahman heifer fertility will likely increase the frequency of the T allele of rs109815800, which may also increase herd profitability and long-term sustainability through improved reproductive efficiency and reduced mature cow size.
Lay Summary
PLAG1 is a gene with allelic variation that has well-documented associations with stature and age at puberty in cattle. Here we extend knowledge of the effect of the PLAG1 alleles to later in life female fertility, as well as size and growth, in Australian Brahmans. Records were collected from 2,839 genotyped Brahman cows and used to generate fertility, growth, and weight phenotypes. A variant on chromosome 14 in PLAG1 (rs109815800) was previously determined to be highly associated with variation in cattle stature. The allele combination (the genotype) at this position was isolated for each animal and the effect of PLAG1 genotype on each trait was estimated using linear modeling. Regardless of how heifer fertility was measured, there was a significant and desirable relationship between PLAG1 genotype and successful heifer fertility. However, the effects of allele combination on fertility began to diminish as cows aged and did not significantly influence stayability at later ages. While there was no effect of genotype on growth, PLAG1 had a negative effect on mature cow weight. Selection emphasis on improved Brahman heifer fertility will likely increase the frequency of the desirable PLAG1 allele, which may have additional benefits on herd profitability and long-term sustainability.
An allele of PLAG1 genotype had a significant and positive relationship with Brahman heifer fertility, although the effect on fertility diminished as cows aged. While there was no effect of PLAG1 genotype on growth, there was a significant and negative relationship of the allele improving heifer fertility with mature cow weight.
Genome-Wide Association Studies (GWAS) in large human cohorts have identified thousands of loci associated with complex traits and diseases. For identifying the genes and gene-associated variants ...that underlie complex traits in livestock, especially where sample sizes are limiting, it may help to integrate the results of GWAS for equivalent traits in humans as prior information. In this study, we sought to investigate the usefulness of results from a GWAS on human height as prior information for identifying the genes and gene-associated variants that affect stature in cattle, using GWAS summary data on samples sizes of 700,000 and 58,265 for humans and cattle, respectively. Using Fisher's exact test, we observed a significant proportion of cattle stature-associated genes (30/77) that are also associated with human height (odds ratio = 5.1, p = 3.1e-10). Result of randomized sampling tests showed that cattle orthologs of human height-associated genes, hereafter referred to as candidate genes (C-genes), were more enriched for cattle stature GWAS signals than random samples of genes in the cattle genome (p = 0.01). Randomly sampled SNPs within the C-genes also tend to explain more genetic variance for cattle stature (up to 13.2%) than randomly sampled SNPs within random cattle genes (p = 0.09). The most significant SNPs from a cattle GWAS for stature within the C-genes did not explain more genetic variance for cattle stature than the most significant SNPs within random cattle genes (p = 0.87). Altogether, our findings support previous studies that suggest a similarity in the genetic regulation of height across mammalian species. However, with the availability of a powerful GWAS for stature that combined data from 8 cattle breeds, prior information from human-height GWAS does not seem to provide any additional benefit with respect to the identification of genes and gene-associated variants that affect stature in cattle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Orthologous positions of 55 genes associated with height in four human populations were located on the bovine genome. Single nucleotide polymorphisms close to eight of these genes were significantly ...associated with stature in cattle (Bos taurus and Bos indicus). This suggests that these genes may contribute to controlling stature across mammalian species.
The causes of temporal fluctuations in adult traits are poorly understood. Here, we investigate the genetic determinants of within-person trait variability of 8 repeatedly measured anthropometric ...traits in 50,117 individuals from the UK Biobank. We found that within-person (non-directional) variability had a SNP-based heritability of 2-5% for height, sitting height, body mass index (BMI) and weight (P
2.4 × 10
). We also analysed longitudinal trait change and show a loss of both average height and weight beyond about 70 years of age. A variant tracking the Alzheimer's risk APOE-
allele (rs429358) was significantly associated with weight loss (
= -0.047 kg per yr, s.e. 0.007, P = 2.2 × 10
), and using 2-sample Mendelian Randomisation we detected a relationship consistent with causality between decreased lumbar spine bone mineral density and height loss (b
= 0.011, s.e. 0.003, P = 3.5 × 10
). Finally, population-level variance quantitative trait loci (vQTL) were consistent with within-person variability for several traits, indicating an overlap between trait variability assessed at the population or individual level. Our findings help elucidate the genetic influence on trait-change within an individual and highlight disease risks associated with these changes.
Key message
Heuristic genomic inbreeding controls reduce inbreeding in genomic breeding schemes without reducing genetic gain
.
Genomic selection is increasingly being implemented in plant breeding ...programs to accelerate genetic gain of economically important traits. However, it may cause significant loss of genetic diversity when compared with traditional schemes using phenotypic selection. We propose heuristic strategies to control the rate of inbreeding in outbred plants, which can be categorised into three types: controls during mate allocation, during selection, and simultaneous selection and mate allocation. The proposed mate allocation measure
GminF
allocates two or more parents for mating in mating groups that minimise coancestry using a genomic relationship matrix. Two types of relationship-adjusted genomic breeding values for parent selection candidates (
GEBV
~
P
) and potential offspring (
GEBV
~
O
) are devised to control inbreeding during selection and even enabling simultaneous selection and mate allocation. These strategies were tested in a case study using a simulated perennial ryegrass breeding scheme. As compared to the genomic selection scheme without controls, all proposed strategies could significantly decrease inbreeding while achieving comparable genetic gain. In particular, the scenario using
GEBV
~
O
in simultaneous selection and mate allocation reduced inbreeding to one-third of the original genomic selection scheme. The proposed strategies are readily applicable in any outbred plant breeding program.
BACKGROUND: Inbreeding reduces the fitness of individuals by increasing the frequency of homozygous deleterious recessive alleles. Some insight into the genetic architecture of fitness, and other ...complex traits, can be gained by using single nucleotide polymorphism (SNP) data to identify regions of the genome which lead to reduction in performance when identical by descent (IBD). Here, we compared the effect of genome-wide and location-specific homozygosity on fertility and milk production traits in dairy cattle. METHODS: Genotype data from more than 43 000 SNPs were available for 8853 Holstein and 4138 Jersey dairy cows that were part of a much larger dataset that had pedigree records (338 696 Holstein and 64 049 Jersey animals). Measures of inbreeding were based on: (1) pedigree data; (2) genotypes to determine the realised proportion of the genome that is IBD; (3) the proportion of the total genome that is homozygous and (4) runs of homozygosity (ROH) which are stretches of the genome that are homozygous. RESULTS: A 1% increase in inbreeding based either on pedigree or genomic data was associated with a decrease in milk, fat and protein yields of around 0.4 to 0.6% of the phenotypic mean, and an increase in calving interval (i.e. a deterioration in fertility) of 0.02 to 0.05% of the phenotypic mean. A genome-wide association study using ROH of more than 50 SNPs revealed genomic regions that resulted in depression of up to 12.5 d and 260 L for calving interval and milk yield, respectively, when completely homozygous. CONCLUSIONS: Genomic measures can be used instead of pedigree-based inbreeding to estimate inbreeding depression. Both the diagonal elements of the genomic relationship matrix and the proportion of homozygous SNPs can be used to measure inbreeding. Longer ROH (>3 Mb) were found to be associated with a reduction in milk yield and captured recent inbreeding independently and in addition to overall homozygosity. Inbreeding depression can be reduced by minimizing overall inbreeding but maybe also by avoiding the production of offspring that are homozygous for deleterious alleles at specific genomic regions that are associated with inbreeding depression.
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