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Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins.

ABSTRACT: Since milk yield is a highly important economic trait in dairy cattle, the genome-wide association study (GWAS) is vital to explain the genetic architecture underlying milk yield and to perform marker-assisted selection (MAS). In this study, we adopted a haplotype-based empirical Bayesian GWAS to identify the loci and candidate genes for milk yield. A total of 1 092 Holstein cows were sequenced by using the genotyping by genome reducing and sequencing (GGRS) method. After filtering, 164 312 high-confidence SNPs and 13 476 haplotype blocks were identified to use for GWAS. The results indicated that 17 blocks were significantly associated with milk yield. We further identified the nearest gene of each haplotype block and annotated the genes with milk-associated quantitative trait locus (QTL) intervals and ingenuity pathway analysis (IPA) networks. Our analysis showed that four genes, DLGAP1, AP2B1, ITPR2 and THBS4, have relationships with milk yield, while another three, ARHGEF4, TDRD1 and KIF19, were inferred to have potential relationships. Additionally, a network derived from the IPA containing one inferred (ARHGEF4) and all four confirmed genes likely regulates milk yield. Our findings add to the understanding of identifying the causal genes underlying milk production traits and could guide follow up studies for further confirmation of the associated genes, pathways and biological networks.

SUBMITTER: Chen Z

PROVIDER: S-EPMC5813974 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins.

Chen Zhenliang Z Yao Yunqiu Y Ma Peipei P Wang Qishan Q Pan Yuchun Y

PloS one 20180215 2

Since milk yield is a highly important economic trait in dairy cattle, the genome-wide association study (GWAS) is vital to explain the genetic architecture underlying milk yield and to perform marker-assisted selection (MAS). In this study, we adopted a haplotype-based empirical Bayesian GWAS to identify the loci and candidate genes for milk yield. A total of 1 092 Holstein cows were sequenced by using the genotyping by genome reducing and sequencing (GGRS) method. After filtering, 164 312 high ...[more]

PMID: 29447209

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Project description:BACKGROUND:Pulmonary hypertension (PH) is a rare disease characterized by proliferation and occlusion of small pulmonary arterioles, which has been associated with a high mortality rate. The pathogenesis of PH is complex and incompletely understood, which includes both genetic and environmental factors that alter vascular structure and function. METHODS:Thus we aimed to reveal the potential genetic etiology of PH by targeting 143 tag SNPs of 14 candidate genes. Totally 208 individuals from Chinese Han population were enrolled in the present study, including 109 non-idiopathic PH patients and 99 healthy controls. RESULTS:The data revealed that 2 SNPs were associated with PH overall susceptibility at p?<?3×10-?4 after Bonferroni correction. The top hit was rs6557421 (p?=?4.5×10-?9), located within Nox3 gene on chromosome 6. Another SNP rs3744439 located in Tbx4 gene, also showed evidence of association with PH susceptibility (p?=?1.2×10-?6). The distribution of genotype frequencies of rs6557421 and rs3744439 have dramatic differences between PH patients and controls. Individuals with rs6557421 TT genotype had a 10.72-fold/14.20-fold increased risk to develop PH when compared with GG or GG/GT carriers in codominant or recessive model, respectively (TT versus GG: 95%CI?=?4.79-24.00; TT versus GG/GT: 95%CI?=?6.65-30.33). As for rs3744439, AG genotype only occurred in healthy controls but has not been observed in PH patients. We further validated the result by using 26 different populations from five regions around the globe, including African (AFR), American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS). In consistent with the present case-control study's results, significantly different genotype frequencies of the observed SNPs existed between PH patients and healthy individuals from all over the world. CONCLUSIONS:The results suggested that rs6557421 variant in Nox3 and rs3744439 variant in Tbx4 might have potential effect on individual susceptibility to pulmonary hypertension, which could lead to therapeutic or diagnosis approaches in PH.

Project description:The gelatinization and retrogradation characteristics of wheat starch affect the eating quality of Chinese-style food. Rapid Visco Analyzer (RVA) parameters have been widely used as important indicators to evaluate and improve the quality of wheat starch. However, the genetic basis of RVA parameters remains to be further explored. In the present study, a natural population was genotyped using 90K single nucleotide polymorphism (SNP) arrays, and the RVA parameters of this population grown in five environments were evaluated. The results showed that 22,068 high-quality SNP markers were identified and distributed unequally on the chromosomes. According to the genetic distance, 214 wheat materials were divided into four groups. Except for the pasting temperature (PTT), six parameters followed a normal distribution. Based on the general linear model, 969 significant association SNPs were detected by genome-wide association studies (GWAS), and chromosomes 7A and 2B had the most associated SNPs. Breakdown viscosity (BV) was associated with the most SNPs (n = 238), followed by PTT (n = 186), peak viscosity (PV; n = 156), trough viscosity (TV; n = 127), and final viscosity (FV; n = 126). According to the average linkage disequilibrium (LD), 33 stable quantitative trait loci (QTLs) were identified for single parameters in multiple environments, of which 12 were associated with BV, followed by peak time (PT; n = 8) and PTT (n = 7). On the other hand, 67 pleiotropic QTLs were identified for multiple parameters. Three candidate genes-TasbeIIa, TasbeI, and TassIIa-were screened for phenotyping analysis. The grain width and the weight of the TasbeIIa and TaSSIIa knockout (KO) lines were significantly lower than those of the TasbeI KO lines and the control (CK). The KO lines had smaller endosperm cells, smaller A-type starch granules, and higher amylose content. The TasbeI KO lines showed normal RVA curves, while the TasbeIIa KO lines showed flat curves. However, the TaSSIIa lines failed to paste under the RVA temperatures. Conclusively, the SNPs/QTLs significantly associated with the RVA parameters and genetic resources with novel haplotypes could be used to improve the quality of wheat starch.

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Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins.

Publications

Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins.

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