Genome-wide association analysis for feed efficiency in Angus cattle

Estimated breeding values for average daily feed intake (AFI; kg/day), residual feed intake (RFI; kg/day) and average daily gain (ADG; kg/day) were generated using a mixed linear model incorporating genomic relationships for 698 Angus steers genotyped with the Illumina BovineSNP50 assay. Association analyses of estimated breeding values (EBVs) were performed for 41,028 single nucleotide polymorphisms (SNPs), and permutation analysis was used to empirically establish the genome-wide significance threshold (P < 0.05) for each trait. SNPs significantly associated with each trait were used in a forward selection algorithm to identify genomic regions putatively harbouring genes with effects on each trait. A total of 53, 66 and 68 SNPs explained 54.12% (24.10%), 62.69% (29.85%) and 55.13% (26.54%) of the additive genetic variation (when accounting for the genomic relationships) in steer breeding values for AFI, RFI and ADG, respectively, within this population. Evaluation by pathway analysis revealed that many of these SNPs are in genomic regions that harbour genes with metabolic functions. The presence of genetic correlations between traits resulted in 13.2% of SNPs selected for AFI and 4.5% of SNPs selected for RFI also being selected for ADG in the analysis of breeding values. While our study identifies panels of SNPs significant for efficiency traits in our population, validation of all SNPs in independent populations will be necessary before commercialization.     

肺结核全基因组关联研究进展

肺结核是由结核分枝杆菌感染引起的一类古老但仍对人类造成巨大影响的传染性疾病。到目前为止, 肺结核依然是由单一病原菌导致死亡人数最多的疾病, 并且随着耐药菌株的出现而呈现死灰复燃之势。近几年, 肺结核全基因组关联研究在世界范围内取得了阶段性成果, 发现了与肺结核相关联的遗传易感位点和区域, 使肺结核的遗传学研究进入了一个崭新的阶段, 为后续肺结核的早期和综合防治提供了重要线索。然而, 由于人群遗传结构差异和宿主/病原体相互作用, 与其他复杂疾病相比, 肺结核全基因组关联研究依旧面临重重困难, 进展缓慢。文章对不同人群肺结核全基因组关联研究及其验证进行综述, 并系统阐述了目前研究中存在的困难及可能的应对策略。     

中国人群肝功能检测指标全基因组关联分析研究

肝功能检测(liver function test, LFTs)指标是受遗传和环境影响的复杂性状,具有个体差异性。为系统性研究中国人群全基因组范围内单核苷酸多态性(single nucleotide polymorphism, SNP)与肝功能指标之间的联系,本研究利用英国生物银行(UK Biobank)中1653名中国人的基因分型数据和表型数据为研究对象,利用PLINK软件进行全关联分析研究(genome-wide association study, GWAS),发现229个SNP与中国人群血液中的总胆红素(total bilirubin, TB)相关,27个SNP与中国人群血液中碱性磷酸酶(alkaline phosphatase, ALP)相关,36个SNP与中国人群血液中的γ-谷氨酰转肽酶(γ-glutamyl transpeptidase, GGT)相关,1个SNP与中国人群血液中的门冬氨酸氨基转移酶(aspartate transaminase, AST)相关,最显著的位点中有11个位点是新的LFTs关联位点。通过功能基因组分析,发现这些位点的临床意义(如吉尔伯特综合征)...     

Effects of ad libitum and restricted feeding on early production performance and body composition of Yorkshire pigs selected for reduced residual feed intake

Residual feed intake (RFI), defined as the difference between observed and expected feed intake based on growth and backfat, has been used to investigate genetic variation in feed efficiency in cattle, poultry and pigs. However, little is known about the biological basis of differences in RFI in pigs. To this end, the objective of this study was to evaluate the fifth generation of a line of pigs selected for reduced RFI against a randomly selected Control line for performance, carcass and chemical carcass composition and overall efficiency. Here, emphasis was on the early grower phase. A total of 100 barrows, 50 from each line, were paired by age and weight (22.6 ± 3.9 kg) and randomly assigned to one of four feeding treatments in 11 replicates: ad libitum (Ad), 75% of Ad (Ad75), 55% of Ad (Ad55) and weight stasis (WS), which involved weekly adjustments in intake to keep body weight (BW) constant for each pig. Pigs were individually penned (group housing was used for selection) and were on treatment for 6 weeks. Initial BW did not significantly differ between the lines (P > 0.17). Under Ad feeding, the low RFI pigs consumed 8% less feed compared with Control line pigs (P < 0.06), had less carcass fat (P < 0.05), but with no significant difference in growth rate (P > 0.85). Under restricted feeding, low RFI pigs under the Ad75 treatment had a greater rate of gain while consuming the same amount of feed as Control pigs. Despite the greater gain, no significant line differences in carcass composition or carcass traits were observed. For the WS treatment, low RFI pigs had similar BW (P > 0.37) with no significant difference in feed consumption (P > 0.32). Overall, selection for reduced RFI has decreased feed intake, with limited differences in growth rate but reduced carcass fat, as seen under Ad feeding. Collectively, results indicate that the effects of selection for low RFI are evident during the early grower stage, which allows for greater savings to the producer.     

Genome-wide association study for longevity in the Holstein cattle population

Longevity is one of the most important traits determining dairy cow profitability. In the last decades dairy cows suffered a lowering in the age at culling. With the aim to identify the genes involved in longevity, dates of birth, yields, dates of calving during lifespan and culling dates were collected for 946 culled cows which had been genotyped with the Bovine High Density panel. Using the GenABEL package in R, genome-wide association analysis was performed on three potential traits of longevity: (1) ‘days in production,’ (2) ‘days in herd,’ (3) number of calvings over lifespan.’ Five genome-wide significant single nucleotide polymorphisms (SNPs) associated with all three longevity traits were detected. Several consecutive SNPs identified on chromosomes 16 and 30 indicated the presence of two suggestive quantitative trait loci (QTL). The genes comprised in the QTL regions had biological functions related to fertility, reproductive disorders, heat stress and welfare of cows. These findings might contribute to improving breeding strategies to improve longevity.     

Genome-wide association study of milk production traits in a crossbred dairy sheep population using three statistical models

Milk production is one of the most important characteristics of dairy sheep, and the identification of genes affecting milk production traits is critical to understanding the genetics and improve milk production in future generations. Three statistical techniques, namely GWAS, ridge-regression BLUP and BayesC , were used to identify SNPs in significant association with three milk production traits (milk yield, fat yield and protein yield) in a crossbred dairy sheep population. The results suggested that chromosomes 1, 3, 4, 5, 7 and 11 were likely to harbor genes important to milk production because these chromosomes had the greatest top-100-SNP variance contributions on the three milk production traits. The GWAS analysis identified between 74 and 288 genome-wide significant SNP (P < 0.05) whereas the BayesCπ model revealed between six and 63 SNPs, each with >95% posterior probability of inclusion as having a non-zero association effect on at least one of the three milk production traits. Positional candidate genes for milk production in sheep were searched, based on the sheep genomic assembly OAR version 3.1, such as those which map position coincided with or was located within 0.1 Mbp of a genome-wide suggestive or significant SNP. These identified SNPs and candidate genes supported some previous findings and also added new information about genetic markers for genetic improvement of lactation in dairy sheep, but keeping in mind that the majority of these positional candidate genes are not necessarily true causative loci for these traits and future validations are thus necessary.     

Genome-wide association study identifies 7q11.22 and 7q36.3 associated with noise-induced hearing loss among Chinese population

Noise-induced hearing loss (NIHL) seriously affects the life quality of humans and causes huge economic losses to society. To identify novel genetic loci involved in NIHL, we conducted a genome-wide association study (GWAS) for this symptom in Chinese populations. GWAS scan was performed in 89 NIHL subjects (cases) and 209 subjects with normal hearing who have been exposed to a similar noise environment (controls), followed by a replication study consisting of 53 cases and 360 controls. We identified that four candidate pathways were nominally significantly associated with NIHL, including the Erbb, Wnt, hedgehog and intraflagellar transport pathways. In addition, two novel index single-nucleotide polymorphisms, rs35075890 in the intron of AUTS2 gene at 7q11.22 (combined P = 1.3 × 10⁻⁶) and rs10081191 in the intron of PTPRN2 gene at 7q36.3 (combined P = 2.1 × 10⁻⁶), were significantly associated with NIHL. Furthermore, the expression quantitative trait loci analyses revealed that in brain tissues, the genotypes of rs35075890 are significantly associated with the expression levels of AUTS2, and the genotypes of rs10081191 are significantly associated with the expressions of PTPRN2 and WDR60. In conclusion, our findings highlight two novel loci at 7q11.22 and 7q36.3 conferring susceptibility to NIHL.     

Phenotypic and genetic relationships between growth and feed intake curves and feed efficiency and amino acid requirements in the growing pig

Improvement of feed efficiency in pigs has been achieved essentially by increasing lean growth rate, which resulted in lower feed intake (FI). The objective was to evaluate the impact of strategies for improving feed efficiency on the dynamics of FI and growth in growing pigs to revisit nutrient recommendations and strategies for feed efficiency improvement. In 2010, three BWs, at 35±2, 63±9 and 107±7 kg, and daily FI during this period were recorded in three French test stations on 379 Large White and 327 French Landrace from maternal pig populations and 215 Large White from a sire population. Individual growth and FI model parameters were obtained with the InraPorc^R software and individual nutrient requirements were computed. The model parameters were explored according to feed efficiency as measured by residual feed intake (RFI) or feed conversion ratio (FCR). Animals were separated in groups of better feed efficiency (RFI⁻ or FCR⁻), medium feed efficiency and poor feed efficiency. Second, genetic relationships between feed efficiency and model parameters were estimated. Despite similar average daily gains (ADG) during the test for all RFI groups, RFI⁻ pigs had a lower initial growth rate and a higher final growth rate compared with other pigs. The same initial growth rate was found for all FCR groups, but FCR⁻ pigs had significantly higher final growth rates than other pigs, resulting in significantly different ADG. Dynamic of FI also differed between RFI or FCR groups. The calculated digestible lysine requirements, expressed in g/MJ net energy (NE), showed the same trends for RFI or FCR groups: the average requirements for the 25% most efficient animals were 13% higher than that of the 25% least efficient animals during the whole test, reaching 0.90 to 0.95 g/MJ NE at the beginning of the test, which is slightly greater than usual feed recommendations for growing pigs. Model parameters were moderately heritable (0.30±0.13 to 0.56±0.13), except for the precocity of growth (0.06±0.08). The parameter representing the quantity of feed at 50 kg BW showed a relatively high genetic correlation with RFI (0.49±0.14), and average protein deposition between 35 and 110 kg had the highest correlation with FCR (−0.76±0.08). Thus, growth and FI dynamics may be envisaged as breeding tools to improve feed efficiency. Furthermore, improvement of feed efficiency should be envisaged jointly with new feeding strategies.     

奶牛重要经济性状全基因组关联分析研究进展

产奶性状是奶牛最重要的生产性状,随着平衡育种理念的提出和发展,繁殖性状、体型性状、健康性状和长寿性等功能性状也逐渐被重视并纳入育种规划中。鉴定产奶性状和功能性状主效基因或遗传标记并将之应用于奶牛标记辅助选择可望加快遗传进展。随着高密度SNP标记的高通量检测技术的发展,全基因组关联分析已成为鉴定畜禽重要经济性状基因的重要途径。文章对奶牛产奶性状和功能性状全基因组关联分析研究进展进行综述。     

奶牛重要经济性状全基因组关联分析研究进展

产奶性状是奶牛最重要的生产性状, 随着平衡育种理念的提出和发展, 繁殖性状、体型性状、健康性状和长寿性等功能性状也逐渐被重视并纳入育种规划中。鉴定产奶性状和功能性状主效基因或遗传标记并将之应用于奶牛标记辅助选择可望加快遗传进展。随着高密度SNP标记的高通量检测技术的发展, 全基因组关联分析已成为鉴定畜禽重要经济性状基因的重要途径。文章对奶牛产奶性状和功能性状全基因组关联分析研究进展进行综述。     

普通菜豆镰孢菌枯萎病抗性种质资源筛选及全基因组关联分析

普通菜豆镰孢菌枯萎病是严重制约菜豆(Phaseolus vulgaris)产量的主要病害之一。采用下胚轴双孔注射法对601份普通菜豆种质资源进行枯萎病抗性鉴定, 共筛选出4份高抗材料。在此基础上, 基于分布在全基因组上的3 765 456个单核苷酸多态性(SNP)标记, 进行全基因组关联分析, 以P<1×10^-5为阈值。结果检测到57个显著关联的SNP位点, 分布于1、2、6、8和11号染色体上; 共获得8个显著关联区域, 其中位于1号染色体上的区域1包含SNP最多(48个), 最显著SNP P值为2.18E-07。在8个显著关联区域中, 共检测到186个基因, 其中157个基因有注释信息, 编码过氧化物酶、抗病蛋白、转录因子和蛋白激酶等。结合KEGG富集分析和序列同源性比对, 鉴定出9个候选基因可能与抗性相关。     

Pulling the covers in electronic health records for an association study with self-reported sleep behaviors

ABSTRACT

The electronic health record (EHR) contains rich histories of clinical care, but has not traditionally been mined for information related to sleep habits. Here, we performed a retrospective EHR study based on a cohort of 3,652 individuals with self-reported sleep behaviors documented from visits to the sleep clinic. These individuals were obese (mean body mass index 33.6 kg/m²) and had a high prevalence of sleep apnea (60.5%), however we found sleep behaviors largely concordant with prior prospective cohort studies. In our cohort, average wake time was 1 hour later and average sleep duration was 40 minutes longer on weekends than on weekdays (p < 10^?12). Sleep duration varied considerably as a function of age and tended to be longer in females and in whites. Additionally, through phenome-wide association analyses, we found an association of long weekend sleep with depression, and an unexpectedly large number of associations of long weekday sleep with mental health and neurological disorders (q < 0.05). We then sought to replicate previously published genetic associations with morning/evening preference on a subset of our cohort with extant genotyping data (n = 555). While those findings did not replicate in our cohort, a polymorphism (rs3754214) in high linkage disequilibrium with a previously published polymorphism near TARS2 was associated with long sleep duration (p < 0.01). Collectively, our results highlight the potential of the EHR for uncovering the correlates of human sleep in real-world populations.     

Genome-wide association study for growth and fatness traits in Chinese Sujiang pigs

Growth and fatness traits are complex and economically important traits in the pig industry. The molecular basis underlying porcine growth and fatness traits remains largely unknown. To uncover genetic loci and candidate genes for these traits, we explored the GeneSeek GGP Porcine 80K SNP chip to perform a GWAS for seven growth and fatness traits in 365 individuals from the Sujiang pig, a recently developed breed in China. We identified two, 17, one and 11 SNPs surpassing the suggestively significant threshold (P < 1.86 × 10⁻⁵) for body weight, chest circumference, chest width and backfat thickness respectively. Of these SNPs, 20 represent novel genetic loci, and five and four SNPs were respectively associated with chest circumference and backfat thickness at a genome-wide significant threshold (P < 9.31 × 10⁻⁷). Eight SNPs had a pleiotropic effect on both chest circumference and backfat thickness. The most remarkable locus resided in a region between 72.95 and 76.27 Mb on pig chromosome 4, harboring a number of previously reported quantitative trait loci related to backfat deposition. In addition to two reported genes (PLAG1 and TAS2R38), we identified four genes including GABRB3, ZNF106, XKR4 and MGAM as novel candidates for body weight and backfat thickness at the mapped loci. Our findings provide insights into the genetic architecture of porcine growth and fatness traits and potential markers for selective breeding of Chinese Sujiang pigs.