Quantitative trait loci for behavioural traits in chickens

The detection of quantitative trait loci (QTL) of behavioural traits has mainly been focussed on mouse and rat. With the rapid development of molecular genetics and the statistical tools, QTL mapping for behavioural traits in farm animals is developing. In chicken, a total of 30 QTL involved in pecking-related traits, open-field behaviour, tonic immobility, response to novel objects, and response to a restraint test were detected in different studies. In the search for a useful early predictor for feather pecking (FP) behaviour in adult laying hens, the following was found: FP in young animals is not a predictor for FP in adult animals, however, open-field behaviour in young animals is genetically correlated with FP in adult hens. Before the implementation of FP behaviour or open-field behaviour in breeding programmes, it is essential to know more about the correlation between these behavioural traits and also their relationship with production traits. Nevertheless, with the QTL for behavioural traits and the chicken genome sequence in progress, a better understanding of the underlying genetic mechanisms of behavioural traits will be feasible.     

Genetic and genomic analyses for predicted methane‐related traits in Japanese Black steers

The objectives of this study were to estimate genetic parameters and to perform a genome‐wide association study (GWAS) for predicted methane‐related traits in Japanese Black steers. The methane production and yield traits were predicted using on‐farm measurable traits, such as dry matter intake and average daily gain. A total of 4,578 Japanese Black steers, which were progenies of 362 sires genotyped with imputed 551,995 single nucleotide polymorphisms (SNPs), had phenotypes of predicted methane‐related traits during the total fattening period (52 weeks). For the estimation of genetic parameters, the estimated heritabilities were moderate (ranged from 0.57 to 0.60). In addition, the estimated genetic correlations of methane production traits with most of carcass traits and feed‐efficiency traits were unfavorable, but those of methane yield traits were favorable or low. For the GWAS, no genome‐wide significant SNP was detected, but a total of four quantitative trait locus (QTL) regions that explained more than 5.0% of genetic variance were localized on the genome, and some candidate genes associated with growth and feed‐efficiency traits were located on the regions. Our results suggest that the predicted methane‐related traits are heritable and some QTL regions for the traits are localized on the genome in Japanese Black steers.     

Evaluation of FABP2 as candidate gene for a fatty acid composition QTL in porcine chromosome 8

The objective of this work was to analyse the porcine Fatty acid binding protein 2, intestinal ( FABP2 ) gene as a candidate gene for a fatty acid composition quantitative trait loci (QTL) previously described on porcine chromosome 8 in an Iberian by Landrace F₂ cross (IBMAP). Re-sequencing of the porcine FABP2 gene in three Iberian and eight Landrace parental animals resulted in the identification of three single-nucleotide polymorphisms, all of them localized in intron 1. The polymorphism FABP2 :g.412T>C, localized in intron 1, and two additional microsatellites were genotyped in the IBMAP population in order to perform an association test of the FABP2 gene and to better define the QTL position previously described. Association analyses of the FABP2 :g.412T>C with the fatty acid composition traits were not significant in simple association and marker-assisted association tests, suggesting that the FABP2 region sequenced is not responsible for the QTL. However, the addition of three new markers to the pedigree allowed us to define the S0144–SW61 marker interval as the most likely QTL position, facilitating the future study of other candidate genes for this QTL.     

Genetic approaches to the improvement of fertility traits in the pig

One of the major determinants for litter size in pigs is prenatal mortality. It occurs most frequently during the first few weeks of gestation and can be attributed to abnormalities in developmental processes during embryogenesis including trophoblastic elongation and blastocyst implantation. Improvement of litter size has been attempted by means of phenotypic selection. However, another promising approach in pursuit of this aim has been the use of genotypic information. Reproductive traits in general are well-suited for application of marker-assisted selection (MAS). The possibility of exerting selection criteria at the molecular level shortens the generation interval as the selection decision can take place early in the life of an animal. Moreover, in consideration of the sex-limited nature of reproductive traits, genotypic information allows for selection in the gender in which the trait cannot be directly observed. Accordingly, there has been considerable interest in mapping and identifying genes involved in the regulation of reproductive traits and in elucidating their expression patterns. This review offers a comprehensive, if not exhaustive, account of the efforts being made and the approaches currently used in this field. One approach has been to choose candidate genes a priori because of the physiological importance of the proteins they encode and their role in the reproduction of other mammals. The usefulness of candidate genes is then examined by association studies between genetic polymorphisms identified in the respective candidate genes and the phenotypic reproductive traits. The other approach discussed uses pre-existing or designed families for linkage analyses in order to map the location of quantitative trait loci (QTL) for the reproductive trait of interest. The results reported were not consistent among different studies but the QTL regions detected may be useful for identification of positional candidate genes in further molecular genetic studies. However, a better understanding of porcine reproduction requires that these functional genomic approaches are merged and integrated with detailed analyses of the proteome to establish linkages between predisposition and physiology.     

Investigation of two candidate genes for meat quality traits in a quantitative trait locus region on SSC6: the porcine short heterodimer partner and heart fatty acid binding protein genes

A highly significant quantitative trait locus (QTL) on pig chromosome 6, affecting intramuscular fat (IMF), has previously been detected by our group and others. Two genes of positional and biological interest, the small heterodimer partner (SHP; NR0B2) and the heart fatty acid binding protein (FABP3; H‐FABP), were investigated for meat quality traits and IMF respectively. SHP was partially sequenced (GenBank: DQ002896 and DQ002897 ) and mapped to the QTL region on porcine chromosome 6, affecting IMF. The map shows no recombination between SHP and FABP3, which was previously mapped to the same QTL region. Twelve single nucleotide polymorphisms were detected in the sequenced region of SHP gene. Haplotype information was used to investigate association between genetic variation and different meat quality traits. SHP haplotype combinations were found to have significant effect on connective tissue. However, further studies are needed to evaluate this possible association more effectively. The FABP3 is involved in fatty acid transport and has been studied as a candidate gene for IMF by several research groups. In our study, FABP3 genotypes were confirmed to be significantly associated with IMF in pigs. The average content of IMF in our population was 1.6%, which may indicate that the FABP3 polymorphism explains as much as 30–35% of the variation in IMF in our pig cross‐population.     

The effect of adipocyte and heart fatty acid-binding protein genes on intramuscular fat and backfat content in Meishan crossbred pigs

Effects of genetic variation in porcine adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, respectively, on intramuscular fat (IMF) content and backfat thickness (BFT) were examined in F2 crossbreds of Meishan and Western pigs. The involvement of each FABP gene in IMF accretion was studied to confirm previous results for Duroc pigs. The F2 crossbred pigs were genotyped for various markers including microsatellite sequences situated within both FABP genes. Linkage analysis assigned the A-FABP and H-FABP genes to marker intervals S0001-S0217 (20 cM) on SSC4 and Sw316-S0003 (16.6 cM) on SSC6, respectively, refining previous chromosomal assignments. Next, the role of both chromosome regions/genes on genetic variation in IMF content and BFT was studied by 1) screening SSC4 and SSC6 for QTL affecting both traits by performing a line-cross analysis and 2) estimation of the effect of individual A-FABP and H-FABP alleles on both traits. In the first analysis, suggestive and chromosome-wise significant evidence for a QTL affecting IMF was detected on SSC6. The H-FABP gene is a candidate gene for this effect because it resides within the large region containing this putative QTL. The second analysis showed a considerable but nonsignificant effect of H-FABP microsatellite alleles on IMF content. Suggestive evidence for a QTL affecting BFT was found on SSC6, but H-FABP was excluded as a candidate gene. In conclusion, present and previous results support involvement of H-FABP gene polymorphisms in IMF accretion independently from BFT in pigs. Therefore, implementation of these polymorphisms in marker-assisted selection to control IMF content independently from BFT may be considered. In contrast to previous findings for Duroc pigs, no evidence was found for an effect of the A-FABP gene on IMF or BFT in this population.     

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle

Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome. Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs). The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy.     

Analysis of the mouse high-growth region in pigs

In the mouse, homozygous animals for the high growth mutation show a 30–50% increase in growth without becoming obese. This region is homologous to the distal part of pig chromosome 5 (SSC5). A previous genome scan detected several quantitative trait loci (QTL) in this region for body composition and meat quality using a three generation Berkshire × Yorkshire resource family. In this study, the effects on swine growth, fat and meat quality traits of three genes previously identified within the mouse high growth region were analysed. The genes studied were CASP2 and RIPKI domain containing adaptor with death domain ( CRADD ), suppressor of cytokine signalling 2 ( SOCS2 ) and plexinC1 ( PLXNC1 ). In addition, the influence of two other genes located very close to this region, namely the plasma membrane calcium-transporting ATPase 1 ( ATP2B1 ) and dual specificity phosphatase 6 ( DUSP6 ) genes, was also investigated. Single nucleotide polymorphisms were identified and used to map these genes to the QTL region on SSC5. Results indicate significant associations between these genes and several phenotypic traits, including fat deposition and growth in pigs. The present study suggests associations of these genes with swine fat and growth related traits, but further studies are needed in order to clearly identify the genes involved in the regulation of the QTL located on SSC5.     

Identification of genomic regions related to age at first calving and first calving interval in water buffalo using single-step GBLUP

In Brazil, water buffaloes have been used to produce milk for mozzarella cheese production. Consequently, the main selection criterion applied for the buffalo genetic improvement is the estimated mozzarella yield as a function of milk, fat and protein production. However, given the importance of reproductive traits in production systems, this study aimed to use techniques for identifying genomic regions that affect the age at first calving (AFC) and first calving interval (FCI) in buffalo cows and to select candidate genes for the identification of QTL and gene expression studies. The single-step GBLUP method was used for the identification of genomic regions. Windows of 1 Mb containing single-nucleotide polymorphisms were constructed and the 10 windows that explained the greatest proportion of genetic variance were considered candidate regions for each trait. Genes present into the selected windows were identified using the UOA_WB_1 assembly as the reference, and their ontology was defined with the Panther tool. Candidate regions for both traits were identified on BBU 3, 12, 21 and 22; for AFC, candidates were detected on BBU 6, 7, 8, 9 and 15 and for first calving interval on BBU 4, 14 and 19. This study identified regions with great contribution to the additive genetic variance of age at first calving and first calving interval in the population of buffalo cows studied. The ROCK2, PMVK, ADCY2, MAP2K6, BMP10 and GFPT1 genes are main candidates for reproductive traits in water dairy buffaloes, and these results may have future applications in animal breeding programs or in gene expression studies of the species.     

Evaluation of association between polymorphism within the thyroglobulin gene and milk production traits in dairy cattle

In dairy cattle, many studies have reported quantitative trait loci (QTL) on the centromeric end of chromosome 14 that affect milk production traits. One of the candidate genes in this QTL region – thyroglobulin (TG) – was previously found to be significantly associated with marbling in beef cattle. Thus, based on QTL studies in dairy cattle and because of possible effects of this gene on fat metabolism, we investigated the association of TG with milk yield and composition in Holstein dairy cattle. A total of 1279 bulls from the Cooperative Dairy DNA Repository Holstein population were genotyped for a single nucleotide polymorphism in TG used previously in beef cattle studies. Analysis of 29 sire families showed no significant association between TG variants and milk production traits. Within‐sire family analysis suggests that TG is neither the responsible gene nor a genetic marker in association with milk production traits.     

Comparative Genomics Approach to Identify Candidate Genetic Loci for Male Fertility

The article presents multi‐species, genome‐wide, comparative approach to review male fertility‐associated loci to contribute to the development of new genetic markers that could be of interest for functional studies and have the potential to be implemented in farm animal breeding programmes. We reviewed 835 male fertility‐associated candidate loci from seven species and presented them as bovine orthologues where possible. The candidate loci were identified exploiting seven different research approaches: (i) data from animal models: mouse transgenics and knock‐outs (569 genes) and random chemical mutagenesis of mouse genome (31); (ii) animal QTL (69); (iii) genes differentially expressed between fertile and subfertile phenotype in humans and mouse (95); (iv) DNA sequence variations that show specific allele‐phenotype interactions (43 in human and 13 in farm animals); (v) germ line‐specific small non‐coding RNAs (47); (vi) testes expressed genes controlling complex differentiation process of mammalian spermatogenesis (6); and (vii) epigenetically regulated genes (4). According to the number of different research approaches reporting effects of individual genes, we selected 33 most promising candidate genes, which were further in silico analysed for expression levels in testes, genetic variability and top biological functions in functional networks. The aim of this study was to review systematically male fertility‐associated candidate loci using integrated information from different study approaches and species, which will further facilitate development of novel genetic markers for selection towards improved fertility in domestic animals.     

Mapping quantitative trait loci for metabolic and cytological fatness traits of connected F2 crosses in pigs

In the present study 3 connected F(2) crosses were used to map QTL for classical fat traits as well as fat-related metabolic and cytological traits in pigs. The founder breeds were Chinese Meishan, European Wild Boar, and Pietrain with to some extent the same founder animals in the different crosses. The different selection history of the breeds for fatness traits as well as the connectedness of the crosses led to a high statistical power. The total number of F(2) animals varied between 694 and 966, depending on the trait. The animals were genotyped for around 250 genetic markers, mostly microsatellites. The statistical model was a multi-allele, multi-QTL model that accounted for imprinting. The model was previously introduced from plant breeding experiments. The traits investigated were backfat depth and fat area as well as relative number of fat cells with different sizes and 2 metabolic traits (i.e., soluble protein content as an indicator for the level of metabolic turnover and NADP-malate dehydrogenase as an indicator for enzyme activity). The results revealed in total 37 significant QTL on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 14, 17, and 18, with often an overlap of confidence intervals of several traits. These confidence intervals were in some cases remarkably small, which is due to the high statistical power of the design. In total, 18 QTL showed significant imprinting effects. The small and overlapping confidence intervals for the classical fatness traits as well as for the cytological and metabolic traits enabled positional and functional candidate gene identification for several mapped QTL.     

Detection of QTL for greasy fleece weight in sheep using a 50 K single nucleotide polymorphism chip

Genome-wide association studies (GWAS) have introduced an influential tool in the search for quantitative trait loci (QTL) influencing economically important traits in sheep. To identify QTL associated with greasy fleece weight, a GWAS with 50 K single nucleotide polymorphisms (SNPs) was performed in a Baluchi sheep population. Association with greasy fleece weights was tested using the software Plink. The results of our GWAS provided three novel SNP markers and candidate genes associated with greasy fleece weight. A total of three chromosome-wide significant associations were detected for SNP on chromosomes 17 and 20 affecting greasy fleece weight across the four shearing. One of the significant SNP markers was located within ovine known genes namely FAM101A. Further investigation of these identified regions in validation studies will facilitate the identification of strong candidate genes for wool production in sheep.     

Progress of genome wide association study in domestic animals

ABSTRACT: Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described.     

Theoretical efficiency of multiple-trait quantitative trait loci-assisted selection

The effectiveness of five selection methods for genetic improvement of net merit comprising trait 1 of low heritability (h² = 0.1) and trait 2 of high heritability (h² = 0.4) was examined: (i) two‐trait quantitative trait loci (QTL)‐assisted selection; (ii) partial QTL‐assisted selection based on trait 1; (iii) partial QTL‐assisted selection based on trait 2; (iv) QTL‐only selection; and (v) conventional selection index without QTL information. These selection methods were compared under 72 scenarios with different combinations of the relative economic weights, the genetic correlations between traits, the ratio of QTL variance to total genetic variance of the trait, and the ratio of genetic variances between traits. The results suggest that the detection of QTL for multiple‐trait QTL‐assisted selection is more important when the index traits are negatively correlated than when they are positively correlated. In contrast to literature reports that single‐trait marker‐assisted selection (MAS) is the most efficient for low heritability traits, this study found that the identified QTL of the low heritability trait contributed negligibly to total response in net merit. This is because multiple‐trait QTL‐assisted selection is designed to maximize total net merit rather than the genetic response of the individual index trait as in the case of single‐trait MAS. Therefore, it is not economical to identify the QTL of the low heritability traits for the improvement of total net merit. The efficient, cost‐effective selection strategy is to identify the QTL of the moderate or high heritability traits of the QTL‐assisted selection index to facilitate total economic returns. Detection of the QTL of the low h² traits for the QTL‐assisted index selection is justified when the low h² traits have high negative genetic correlation with the other index traits and/or when both economic weights and genetic variances of the low h² traits are larger as compared to the other index traits of higher h². This study deals with theoretical efficiency of QTL‐assisted selection, but the same principle applies to SNP‐based genomic selection when the proportion of the genetic variance ‘explained by the identified QTLs’ in this study is replaced by ‘explained by SNPs’.     

玉米持绿相关ＱＴＬ整合图谱构建及一致性ＱＴＬ区域内候选基因发掘

 以玉米高密度遗传连锁图谱ＩＢＭ２２００８Ｎｅｉｇｈｂｏｒｓ为参考图谱,收集来自不同实验中的１７３个玉米持绿相关数量性状位点（ｑｕａｎｔｉｔａｔｉｖｅｔｒａｉｔｌｏｃｕｓ,ＱＴＬ）信息,利用ＢｉｏＭｅｒｃａｔｏｒ２．１软件,构建出玉米持绿相关ＱＴＬ 整合图谱;采用元分析技术,在１,４,５,９号染色体上发掘出５个持绿“一致性”ＱＴＬ 区间。根据“一致性”ＱＴＬ 区间两端标记在玉米物理图谱Ｂ７３ＲｅｆＧｅｎ＿ｖ２上的位置,将“一致性”ＱＴＬ 区间进行物理图谱定位,利用ＰｌａｎｔＧＤＢ（ｈｔｔｐ：／／ｗｗｗ．ｐｌａｎｔｇｄｂ．ｏｒｇ／）在线区段批量下载工具（ｄｏｗｎｌｏａｄｒｅｇｉｏｎｄａｔａ）下载“一致性”区间的１４４５个预测基因序列并进行生物信息学分析,发现预测基因主要参与具体的细胞过程,执行结合功能,催化、转移酶活性和氧化还原酶活性等分子功能。根据“一致性”ＱＴＬ 区间的基因位点名称,在ＮＣＢＩ中下载相关基因序列,与所在“一致性”ＱＴＬ 区 间所有预测基因保守结构域进行比对,在５个“一致性”持绿ＱＴＬ 区间内初步确定８个持绿相关候选基因。利用ＧＲＡＭＥＮＥ 网站（ｈｔｔｐ：／／ｗｗｗ．ｇｒａｍｅｎｅ．ｏｒｇ／）的Ｃｍａｐ功能,将水稻持绿基因狊犵狉（ｓｔａｙｇｒｅｅｎ）转定位于玉米物理图谱Ｂ７３ＲｅｆＧｅｎ＿ｖ２上,找到与其同源的玉米候选基因ＧＲＭＺＭ２Ｇ０９１８３７＿Ｔ０１,其序列与已发表的玉米衰老诱导叶绿体持绿蛋白基因狊犵狉１序列一致。     

畜禽数量性状基因座位的精细定位

数量性状基因座位(QTL)的精细定位是实施QTL克隆及标记辅助选择(MAS)的重要基础。然而就目前畜禽QTL定位的结果来看,除了通过候选基因法识别的少数基因外,大多数QTL定位的精度仍无法满足实际应用的要求。为进一步提高QTL定位的精度,缩小QTL定位的置信区间,人们相继提出并发展了一系列新的QTL定位方法。本文在分析畜禽QTL定位的基本方法及影响畜禽QTL定位精度的主要因素基础上,对提高QTL定位精确性的策略和方法进行了相应的探讨。     

Exclusion of the swine leukocyte antigens as candidate region and reduction of the position interval for the Sus scrofa chromosome 7 QTL affecting growth and fatness

Pig chromosome 7 (SSC 7) has been shown to be rich in QTL affecting performance and quality traits. Most studies mapped the QTL close to the swine leukocyte antigens (SLA), which has a large effect on adaptability and natural selection. Previous comparative mapping studies suggested that the 15-cM region limited by markers LRA1 (mapped at 55 cM) and S0102 (mapped at 70 cM) contains hundreds of genes. To decrease the number of candidate genes, we improved the mapping resolution with a genetic chromosome dissection through a backcross recombinant progeny test program between Meishan (MS) and European (EU; i.e., Large White or Landrace) breeds. Three first-generation backcross--(EU x MS) x EU--and two second-generation backcross--([EU x MS] x EU) x EU--sires carrying a recombination in the QTL mapping interval were progeny-tested (i.e., measured for a total of 44 growth, fatness, carcass and meat quality traits). Progeny family size varied from 29 to 119 pigs. Animals were genotyped for markers covering the region of interest. Progeny-test results allowed the QTL interval to be decreased from 15 to 20 cM down to 10 cM, and even less than 6 cM if we assumed that the EU pigs used in this study share only one QTL allele. Except for a putative QTL affecting some carcass composition traits, the SLA is excluded as a candidate region, suggesting that it might be possible to apply a marker-assisted selection strategy for this QTL, while controlling SLA allele diversity. The strong QTL effects remaining in animals with only 12.5% (issued from first-generation backcross boars) and 6.25% (issued from second-generation back-cross boars) Meishan genetic background shows that epistatic interactions are likely to be limited. Finally, the QTL does not have strong effects on meat quality traits.     

Candidate gene markers associated with somatotropic axis and milk selection.

One of the obstacles to progress in dairy cattle selection is that milk production traits are only expressed after the first calving. However, the use of the quantitative trait loci (QTL) technology will improve the efficiency of dairy industry with a positive image for the consumers. QTL are part of the genome showing a preponderant action and explaining the major part of variation of the trait production. At the present time, the two major strategies developed to detect such QTL are the candidate gene approach and the positional genetics approach. The somatotropic axis contains the most promising candidates in this respect, as it strongly regulates milk production. Then, the identification of favorable QTL associated with the somatotropic axis that are significantly correlated with genetic merits for milk production could lead to more effective selection programs.