| 1. |
- Ibacache Quiroga, Claudia Jimena, et al.
(författare)
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Fine mapping of a calving QTL on Bos taurus autosome 18 in Holstein cattle
- 2016
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Ingår i: Journal of Animal Breeding and Genetics. - : Wiley. - 0931-2668 .- 1439-0388. ; 133, s. 207-218
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Tidskriftsartikel (refereegranskat)abstract
- Decreased calving performance not only directly impacts the economic efficiency of dairy cattle farming but also influences public concern for animal welfare. Previous studies have revealed a QTL on Bos taurus auto- some (BTA) 18 that has a large effect on calving traits in Holstein cattle. In this study, fine mapping of this QTL was performed using imputed high- density SNP chip (HD) genotypes followed by imputed next-generation sequencing (NGS) variants. BTA18 was scanned for seven direct calving traits in 6113 bulls with imputed HD genotypes. SNP rs136283363 (BTA18: 57 548 213) was consistently the most significantly associated SNP across all seven traits [e.g. p-value = 2.04 x 1059 for birth index (BI)]. To finely map the QTL region and to explore pleiotropic effects, we studied NGS variants within the targeted region (BTA18: 57 321 450- 57 625 355) for associations with direct calving traits and with three con- formation traits. Significant variants were prioritized, and their biological relevance to the traits was interpreted. Considering their functional rela- tionships with direct calving traits, SIGLEC12, CD33 and CEACAM18 were proposed as candidate genes. In addition, pleiotropic effects of this QTL region on direct calving traits and conformation traits were observed. However, the extent of linkage disequilibrium combined with the lack of complete annotation and potential errors in the Bos taurus genome assem- bly hampered our efforts to pinpoint the causal mutation.
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| 2. |
- Mao, Jiwei, 1990, et al.
(författare)
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Fine-tuning of p-coumaric acid synthesis to increase (2S)-naringenin production in yeast
- 2023
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Ingår i: Metabolic Engineering. - 1096-7176 .- 1096-7184. ; 79, s. 192-202
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Tidskriftsartikel (refereegranskat)abstract
- (2S)-Naringenin is a key precursor for biosynthesis of various high-value flavonoids and possesses a variety of nutritional and pharmaceutical properties on human health. Systematic optimization approaches have been employed to improve (2S)-naringenin production in different microbial hosts. However, very few studies have focused on the spatiotemporal distribution of (2S)-naringenin and the related pathway intermediate p-coumaric acid, which is an important factor for efficient production. Here, we first optimized the (2S)-naringenin biosynthetic pathway by alleviating the bottleneck downstream of p-coumaric acid and increasing malonyl-CoA supply, which improved (2S)-naringenin production but significant accumulation of p-coumaric acid still existed extracellularly. We thus established a dual dynamic control system through combining a malonyl-CoA biosensor regulator and an RNAi strategy, to autonomously control the synthesis of p-coumaric acid with the supply of malonyl-CoA. Furthermore, screening potential transporters led to identification of Pdr12 for improved (2S)-naringenin production and reduced accumulation of p-coumaric acid. Finally, a titer of 2.05 g/L (2S)-naringenin with negligible accumulation of p-coumaric acid was achieved in a fed batch fermentation. Our work highlights the importance of systematic control of pathway intermediates for efficient microbial production of plant natural products.
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| 3. |
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| 4. |
- Mao, Xiaowei, et al.
(författare)
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CEACAM18 as candidate for the Holstein calving QTL on BTA18
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A genome-wide association study of Nordic Holstein cattle SNP chip genotypes and imputed next generation sequencing (NGS) variants identified carcinoembryonic antigen-related cell adhesion molecule 18 (CEACAM18) on BTA18 as the gene most highly significantly associated with direct calving traits. Phenotypes used were estimated breeding values (EBV) for six direct calving traits and one compound index trait. A SNP by SNP mixed model approach was first applied using HD genotypes. Haplotypes in the significant region were fitted in a mixed model. Finally, NGS variants in the significant region were utilized to precisely locate causative mutations. Results identified 21 QTL regions associated with one or more calving traits on 16 autosomes. These findings contribute to an improved understanding of the genetic architecture of the calving traits. They may help in improving calving performance in dairy breeding programs.
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| 5. |
- Mao, Xiaowei, et al.
(författare)
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Genome-wide association mapping for dominance effects in female fertility using real and simulated data from Danish Holstein cattle
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Exploring dominance variance and loci contributing to dominance variation is important to understand the genetic architecture behind quantitative traits. The objectives of this study were i) to estimate dominance variances, ii) to detect quantitative trait loci (QTL) with dominant effects, and iii) to evaluate the power and the precision of identifying loci with dominance effect through post-hoc simulations, with applications for female fertility in Danish Holstein cattle. The female fertility records analyzed were number of inseminations (NINS), days from calving to first insemination (ICF), and days from the first to last insemination (IFL), covering both abilities to recycle and to get pregnant in the female reproductive cycle. There were 3,040 heifers and 4,483 cows with both female fertility records and Illumina BovineSNP50 BeadChip genotypes (35,391 single nucleotide polymorphisms (SNP) after quality control). Genomic best linear unbiased prediction (BLUP) models were used to estimate additive and dominance genetic variances. Linear mixed models were used for association analyses. A post-hoc simulation study was performed using genotyped heifers' data. In heifers, estimates of dominance genetic variances for female fertility traits were larger than additive genetic variances, but had large standard errors. The variance components for fertility traits in cows could not be estimated due to non-convergence of the statistical model. In total, five QTL located on chromosomes 9, 11 (2 QTL), 19, and 28 were identified and all of them showed both additive and dominance genetic effects. Among them, the SNP rs29018921 on chromosome 9 is close to a previously identified QTL in Nordic Holstein for interval between first and last insemination. This SNP is located in the 3' untranslated region of gene peptidylprolyl isomerase like 4 (PPIL4), which was shown to be associated with milk production traits in US Holstein cattle but not known for fertility-related functions. Simulations indicated that the current sample size had limited power to detect QTL with dominance effects for female fertility probably due to low QTL variance. More females need to be genotyped to achieve reliable mapping of QTL with dominance effects for female fertility.
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| 6. |
- Mao, Xiaowei, et al.
(författare)
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Genome-wide association studies of growth traits in three dairy cattle breeds using whole-genome sequence data
- 2016
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Ingår i: Journal of Animal Science. - : Oxford University Press (OUP). - 0021-8812 .- 1525-3163. ; 94, s. 1426-1437
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Tidskriftsartikel (refereegranskat)abstract
- Male calves and culled cows of dairy cattle are used for beef production. However, unlike beef breeds, the genetics of growth performance traits in dairy breeds have not been extensively studied. Here, we performed a genome-wide association study (GWAS) on Holsteins (n = 5,519), Jerseys (n = 1,231), and Red Dairy Cattle (n = 4,410) to identify QTL for growth traits. First, a GWAS was performed within breeds using whole-genome sequence variants. Later, a meta-analysis was performed to combine information across the 3 breeds. We have identified several QTL that have large effects on growth traits in Holsteins and Red Dairy Cattle but with little overlap across breeds. Only 1 QTL located on chromosome 10 was shared between Holsteins and Red Dairy Cattle. The most significant variant (BTA10:59,164,533, rs43636323; P-value = 2.8 × 10-32) in this QTL explained 2.4% of the total additive genetic variance in Red Dairy Cattle. The gene CYP19A1 is a strong candidate for the underlying gene of this QTL. In Red Dairy Cattle, a QTL near 25 Mb on chromosome 14 was very significantly associated with growth traits, consistent with the previously reported gene PLAG1, which affects growth in beef cattle and humans. No QTL for growth performance was statistically significant in Jerseys, possibly due to the low power of detection with the small sample size. The meta-analysis of the 3 breeds increased the power to detect QTL.
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| 7. |
- Mao, Xiaowei
(författare)
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Population level genome-wide association studies in dairy cattle
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, genome-wide association studies (GWAS) has become a dominant tool for detecting genetic architectures for complex traits. Thousands of associated genetic variants have been reported. However, the resolution of these studies was limited by the available marker density for the quantitative trait loci (QTL) region. Moreover, the X chromosome and non-additive genetic effects has often been excluded from GWAS, despite of their potentially important biological functions. In chapter 2, we carried out the fine-mapping of a previously reported QTL in Holstein cattle on Bos taurus autosome 18 (BTA18) for calving traits, using imputed high-density SNP chip (HD) genotypes followed by imputed whole-genome sequence (WGS) variants. Genes SIGLEC12, CD33 and CEACAM18 were proposed as candidate genes. In addition, pleiotropic effects of this QTL region were observed on direct calving traits and conformation traits. In chapter 3, we performed a GWAS for growth traits in Nordic Holstein, Jersey, and Red Dairy Cattle. First, GWAS was performed within breeds using WGS variants. Then a meta-analysis was performed to combine information across the three breeds. Several QTL were identified to have large effects on growth traits in Holstein and Red Dairy Cattle, but only one QTL located nearby gene CYP19A1 on chromosome 10 was shared between Holstein and Red Dairy Cattle. Meta-analysis of these three breeds enhanced the power to detect QTL. In chapter 4, we performed the imputation of markers on the X chromosome in Holstein cattle for non-genotyped animals and animals genotyped with low density (Illumina BovineLD) chips, using animals genotyped with medium density (Illumina BovineSNP50) chips. We found that the imputation accuracy of markers on the X chromosome was improved by treating the pseudoautosomal region as autosomal and by increasing the proportion of females in the reference group. In chapter 5, we aimed to detect dominance effects on female fertility traits in Danish Holstein cattle using Illumina BovineSNP50 data, and evaluate the power, precision, and type 1 error of detecting dominance effects through simulations. Four QTL were detected for IFL in heifers, while one QTL was detected for cows. All these five QTL were detected with significant additive and dominance effects. Simulations showed that the current sample size had limited power to detect dominance effects for female fertility in cattle.
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| 8. |
- Mao, Xiaowei, et al.
(författare)
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Short communication: Imputation of markers on the bovine X chromosome
- 2016
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Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 99, s. 7313-7318
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Tidskriftsartikel (refereegranskat)abstract
- Imputation is a cost-effective approach to augment marker data for genomic selection and genome-wide association studies. However, most imputation studies have focused on autosomes. Here, we assessed the imputation of markers on the X chromosome in Holstein cattle for nongenotyped animals and animals genotyped with low-density (Illumina BovineLD, Illumina Inc., San Diego, CA) chips, using animals genotyped with medium-density (Illumina BovineSNP50) chips. A total of 26,884 genotyped Holstein individuals genotyped with medium-density chips were used in this study. Imputation was carried out using FImpute V2.2. The following parameters were examined: treating the pseudoautosomal region as autosomal or as X specific, different sizes of reference groups, different male/female proportions in the reference group, and cumulated degree of relationship between the reference group and target group. The imputation accuracy of markers on the X chromosome was improved if the pseudoautosomal region was treated as autosomal. Increasing the proportion of females in the reference group improved the imputation accuracy for the X chromosome. Imputation for nongenotyped animals in general had lower accuracy compared with animals genotyped with the low-density single nucleotide polymorphism array. In addition, higher cumulative pedigree relationships between the reference group and the target animal led to higher imputation accuracy. In the future, better marker coverage of the X chromosome should be developed to facilitate genomic studies involving the X chromosome.
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