Stories and Challenges of Genome Wide Association Studies in Livestock — A Review

Undoubtedly livestock is one of the major contributors to the economy of any country. The economic value of livestock includes meat, dairy products, fiber, fertilizer etc. Understanding and identifying the associations of quantitative trait loci (QTL) with the economically important traits is believed to substantially benefit the livestock industry. The past two decades have seen a flurry of interest in mapping the QTL associated with traits of economic importance on the genome. With the availability of single nucleotide polymorphism chip of various densities it is possible to identify regions, QTL and genes on the genome that explain the association and its effect on the phenotype under consideration. Remarkable advancement has been seen in genome wide association studies (GWAS) since its inception till the present day. In this review we describe the progress and challenges of GWAS in various livestock species

IL-1β induces expression of proinflammatory cytokines and migration of human colon cancer cells through upregulation of SIRT1

SIRT1 is a mammalian NAD+-dependent deacetylase, which is known to be involved in various physiological events, such as adaptive response to environmental stresses including caloric restriction, as well as in aging and cellular senescence. However, recent studies have revealed overexpression of SIRT1 in many different types of human malignancies, particularly colon cancer. Interleukin-1? (IL-1?) is a proinflammatory cytokine that plays a major role in invasiveness, stemness and progression of colon cancer. However, the interaction between IL-1? and SIRT1 in the tumor development and progression remains elusive. In this study, we found that IL-1? induces SIRT1 protein expression in human colon cancer HCT-116 cells. IL-1?-induced SIRT1 upregulation led to enhanced expression of mRNA transcripts of pro-inflammatory cytokines, IL-6 and IL-8 as well as that of IL-1?. Knockdown of SIRT1 prevented IL-1?-induced phosphorylation and nuclear accumulation of c-Jun. Furthermore, pharmacologic inhibition of SIRT1 abrogated clonogenicity and migrative capability of human colon cancer cells stimulated with IL-1?. In summary, IL-1?-induced SIRT1 upregulation stimulates production of proinflammatory cytokines via a nuclear accumulation of c-Jun, leadng to colon cancer growth and progression.

ARD1 stabilizes NRF2 through direct interaction and promotes colon cancer progression

Aims: Aberrant overactivation/overexpression of NRF2 is implicated as a driving event in tumor progression, which has been attributed to its mutation or inactivation of the inhibitory protein, KEAP1. However, alternative mechanisms responsible for sustained activation of NRF2 are less understood.Main methods: Human colon cancer cell lines and tissues obtained from colorectal cancer (CRC) patients were used. To examine the expression levels of ARD1 and NRF2, Western blot and immunofluorescence analyses were performed. To investigate the potential relevance of NRF2 and ARD1 to human CRC, NRF2 and ARD1 were individually silenced in human colon cancer cells (HCT-116) by transfection with their specific small interfering RNA (siRNA). To determine the functional role of ARD1 in NRF2 regulation, in situ proximate ligation, coimmunoprecipitation, nano-LC-ESI MS/MS, and in vitro acetylation assays were performed.Key findings: ARD1 knockdown in human colon cancer cell lines significantly reduced the protein levels of NRF2 without affecting its mRNA expression; however, silencing of NRF2 did not alter ARD1 protein expression. In addition, these two proteins were co-localized and physically interacted with each other both in human colon cancer cells (HCT-116) and human colon tumor tissues. Mechanistically, ARD1 overexpression increased the acetylation levels of NRF2. Moreover, an in vitro acetylation assay and mass spectrometric analysis demonstrated that ARD1 could directly acetylate NRF2. Ectopic expression of mutant forms of ARD1 with defective acetyltransferase activity reduced the stability of NRF2.Significance: In conclusion, ARD1 may potentiate the oncogenic function of NRF2 in human colon cancer by stabilizing this transcription factor.N

Expressed Sequence Tags Analysis and Design of Simple Sequence Repeats Markers from a Full-Length cDNA Library in Perilla frutescens (L.)

Perilla frutescens is valuable as a medicinal plant as well as a natural medicine and functional food. However, comparative genomics analyses of P. frutescens are limited due to a lack of gene annotations and characterization. A full-length cDNA library from P. frutescens leaves was constructed to identify functional gene clusters and probable EST-SSR markers via analysis of 1,056 expressed sequence tags. Unigene assembly was performed using basic local alignment search tool (BLAST) homology searches and annotated Gene Ontology (GO). A total of 18 simple sequence repeats (SSRs) were designed as primer pairs. This study is the first to report comparative genomics and EST-SSR markers from P. frutescens will help gene discovery and provide an important source for functional genomics and molecular genetic research in this interesting medicinal plant

Genetic Evaluation of Carcass Traits of Commercial Steers at Different Slaughter End–points

Carcass records, including pedigree, for 10,441 steers born from 2003 to 2008 and 21,711 animals total, were made available by the Pyengchang Youngwal Jungsun Livestock Cooperative. Data for each trait were adjusted for each of 5 end-points: age (EPA), back fat (EPB), carcass weight (EPC), eye muscle area (EPE), and marbling score (EPM), and adjustments were made by fitting a linear. Genetic parameters were estimated using ASREML, which uses an average information algorithm. At different slaughter end-points, heritability estimates for CWT (range=0.25 to 0.37) and EMA (range=0.17 to 0.33) were more significantly different than heritability estimates for BF (range=0.41 to 0.42) and MS (range=0.40 to 0.45). Genetic correlations between BF and CWT, EMA and CWT, and EMA and MS were positive, and those between BF and EMA and BF and MS were negative. The genetic correlation between CWT and MS yielded conflicting results. Correlations of sire breeding value for BF, CWT, EMA, and MS were in the range of 0.91 to 0.99, 0.75 to 0.93, 0.72 to 0.95, and 0.90 to 0.99, respectively, and those of the dam were in the range of 0.90 to 0.97, 0.73 to 0.94, 0.71 to 0.94, and 0.91 to 0.99, respectively. Further study will be needed to determine whether these alternative end-points result in a more accurate estimate of BV than the traditional age end-point

Resolvin D1 suppresses inflammation-associated tumorigenesis in the colon by inhibiting IL-6-induced mitotic spindle abnormality

While failure in resolution of inflammation is considered to increase the risk of tumorigenesis, there is paucity of experimental as well as clinical evidence supporting this association. Resolvin D1 (RvD1) is a representative pro-resolving lipid mediator that is endogenously generated from docosahexaenoic acid for the resolution of inflammation. Here, we report a decreased level of RvD1 in the blood from colorectal cancer patients and mice having inflammation-induced colon cancer, suggesting plasma RvD1 as a potential biomarker for monitoring colorectal cancer. Administration of RvD1 attenuated dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM) plus DSS-induced colorectal carcinogenesis by suppressing the production of interleukin-6 (IL-6) and IL-6-mediated chromosomal instability. The protective effect of RvD1 against chromosomal instability is associated with downregulation of IL-6-induced Cyclin D1 expression, which appears to be mediated by blocking the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) axis. RvD1 inhibited the STAT3 signaling pathway by interfering with the binding of IL-6 to its receptor (IL-6R), suggesting the novel function of RvD1 as a putative IL-6R antagonist. Together, our findings suggest that RvD1-mediated blockade of IL-6 signal transmission may contribute to inhibition of chromosomal instability and tumorigenesis.

Genome-Wide Association Study Identifies Major Loci for Carcass Weight on BTA14 in Hanwoo (Korean Cattle)

<div><p>This genome-wide association study (GWAS) was conducted to identify major loci that are significantly associated with carcass weight, and their effects, in order to provide increased understanding of the genetic architecture of carcass weight in Hanwoo. This genome-wide association study identified one major chromosome region ranging from 23 Mb to 25 Mb on chromosome 14 as being associated with carcass weight in Hanwoo. Significant Bonferroni-corrected genome-wide associations (<i>P<1.52</i>×<i>10⁻⁶</i>) were detected for 6 Single Nucleotide Polymorphic (SNP) loci for carcass weight on chromosome 14. The most significant SNP was <i>BTB-01280026</i> (<i>P = 4.02×10⁻¹¹</i>), located in the 25 Mb region on Bos taurus autosome 14 (BTA14). The other 5 significant SNPs were <i>Hapmap27934-BTC-065223</i> (<i>P = 4.04×10⁻¹¹</i>) in 25.2 Mb, <i>BTB-01143580</i> (<i>P = 6.35×10⁻¹¹</i>) in 24.3 Mb, <i>Hapmap30932-BTC-011225</i> (<i>P = 5.92×10⁻¹⁰</i>) in 24.8 Mb, <i>Hapmap27112-BTC-063342</i> (<i>P = 5.18×10⁻⁹</i>) in 25.4 Mb, and <i>Hapmap24414-BTC-073009</i> (<i>P = 7.38×10⁻⁸</i>) in 25.4 Mb, all on BTA 14. One SNP (<i>BTB-01143580; P = 6.35×10⁻¹¹</i>) lies independently from the other 5 SNPs. The 5 SNPs that lie together showed a large Linkage disequilibrium (LD) block (block size of 553 kb) with LD coefficients ranging from 0.53 to 0.89 within the block. The most significant SNPs accounted for 6.73% to 10.55% of additive genetic variance, which is quite a large proportion of the total additive genetic variance. The most significant SNP (<i>BTB-01280026; P = 4.02×10⁻¹¹</i>) had 16.96 kg of allele substitution effect, and the second most significant SNP (<i>Hapmap27934-BTC-065223; P = 4.04×10⁻¹¹</i>) had 18.06 kg of effect on carcass weight, which correspond to 44% and 47%, respectively, of the phenotypic standard deviation for carcass weight in Hanwoo cattle. Our results demonstrated that carcass weight was affected by a major Quantitative Trait Locus (QTL) with a large effect and by many SNPs with small effects that are normally distributed.</p></div

Effect of the most significantly associated SNPs (<i>BTB_01143580</i> and <i>BTB_01280026</i>) on the carcass weight in the Hanwoo breed.

<p>The boxplots show the effects of the most significantly associated two SNPs and their haplotypes on the carcass weight.</p