Cluster of differentiation 4 (CD4) is the accessory protein non-covalently bound to the T cell receptor that recognizes an invariant region of MHC class II on antigen presenting cells. Its cytoplasmic tail, physically associated with a protein tyrosine kinase, is important in the activation of helper/inducer T lymphocytes. In Bos taurus, CD4 gene is located on chromosome 5 from which two isoforms are transcribed, with a different number of amino acids due to splicing of exon 7 and variation in the reading frame. The aim of this study was to investigate the sequence of the entire CD4 gene in Simmental sires to evaluate the effects of genomic variants on the indexes of the bulls for milk, fat and protein yields, as well as somatic cell score. The associations among genomic variants and indexes were analysed using the Allele and GLM procedures of SAS 9.4. The analysis indicated that only four of the thirty-one identified SNPs influenced the considered traits. Identified variants insist on coding zones and intronic sequences, where we revealed the presence of sites for transcription factors. To evaluate the existence of haplotypic effects, combinations among the four genomic variants (SNP 3, SNP 8, SNP 11 and SNP 19) were investigated. Six different haplotypic alleles were identified, but only four of them were frequent enough to allow for an evaluation of any haplotypic effect (at least six copies in the examined sample): Hap1, Hap2, Hap3 and Hap6. The analysis of associations between the selected haplotypes in the CD4 gene with milk related indexes showed that bulls with Hap2 (T-A-C-C) had better indexes for milk and protein yields (P < 0.05), whereas the presence of the Hap1 haplotype (A-G-A-T) caused a significant decrease of the index for protein yield (P < 0.05). Frequencies of the two alleles Hap1 and Hap2 (9 and 36% respectively) make them of interest for their possible inclusion in breeding schemes and support the hypothesis of considering this gene as a candidate for the improvement of milk-related traits in the Simmental breed.

The objectives of the current study were to detect putative genomic loci and to identify candidate genes associated with milk production traits in Egyptian buffalo. A total number of 161 479 daily milk yield (DMY) records and 60 318 monthly measures for fat and protein percentages (FP and PP, respectively), along with fat and protein yields (FY and PY, respectively) from 1670 animals were used. Genotyping was performed using Axiom® Buffalo Genotyping 90 K array. Genome-wide association study (GWAS) for each trait was performed using PLINK. After Bonferroni correction, 47 SNPs were associated with one or more milk production traits. These SNPs were distributed over 36 quantitative trait loci (QTL) and located on 20 buffalo chromosomes (BBU). For the 47 SNPs, one was overlapped for three traits (DMY, FY, and PY), six were associated with two traits (one for PP and PY and five for FY and PY) while the rest were associated with only one trait. Out of 36 identified QTL, eleven were overlapped with previously reported loci in buffalo and/or cattle populations. Some of these SNPs are placed within or close to potential candidate genes, for example: TPD52, ZBTB10, RALYL and SNX16 on BBU15, ADGRD1 on BBU17, ESRRG on BBU5 and GRIP1 on BBU4. This is the first reported study between genome-wide markers and milk components in Egyptian buffalo. Our findings provide useful information to explore the genetic mechanisms and relevant genes contributing to the variation in milk production traits. Further confirmation studies with larger population size are necessary to validate the findings and detect the causal genetic variants.

Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e−14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.

The etiology of suicide is complex in nature with both environmental and genetic causes that are extremely diverse. This extensive heterogeneity weakens the relationship between genotype and phenotype and as a result, we face many challenges when studying the genetic etiology of suicide. We are now in the midst of a genetics revolution, where genotyping costs are decreasing and genotyping speed is increasing at a fast rate, allowing genetic association studies to genotype thousands to millions of SNPs that cover the entire human genome. As such, genome-wide association studies (GWAS) are now the norm. In this article we address several statistical challenges that occur when studying the genetic etiology of suicidality in the age of the genetics revolution. These challenges include: (1) the large number of statistical tests; (2) complex phenotypes that are difficult to quantify; and (3) modest genetic effect sizes. We address these statistical issues in the context of family-based study designs. Specifically, we discuss several statistical extensions of family-based association tests (FBATs) that work to alleviate these challenges. As our intention is to describe how statistical methodology may work to identify disease variants for suicidality, we avoid the mathematical details of the methodologies presented.

Birth weight is the earliest available growth trait with considerable impacts on lamb survivability and growth performance traits. This study was conducted to perform a genome-wide association study of birth weight in a meat-type sheep. A total of 132 Lori-Bakhtiari sheep were selected based on estimated of breeding values (EBVs) for BW analyses. The selected animals were genotyped using Illumina Ovine SNP50 Bead Chip. After quality control, a total of 41 323 single-nucleotide polymorphisms (SNPs) and 130 sheep were used for subsequent analyses. Plink 1.90 beta software was used for the analyses. Seven SNPs on chromosomes 1, 16, 19 and 22 were detected based on genome-wide unadjusted P-values (P <10−6), which jointly accounted for 1.2% of total genetic variation. However, based on Bonferroni-adjusted P-values, only three SNPs on chromosome 1 had significant associations with EBVs for birth weight (P <0.05), which jointly explained 0.8% of total genetic variation. A total of seven genes were found in 50 kb intervals from the three significant SNPs on chromosome 1, but only three genes, including RAB6B (a member of RAS oncogene family), Tf serotransferrin and GIGYF2 (a GRB10 interacting GYF protein 2), could be considered as candidate genes for birth weight in future studies. The results of this study may facilitate potential use of the genes involving in growth and production traits for genetic improvement of productivity in sheep.

The aims of this study were to estimate the genetic variation of traditional milk coagulation properties (MCPs), milk acidity, curd firmness (CF) modeled on time t (CFt; comprising: RCTeq, rennet coagulation time estimated from the equation; CFP, the asymptotic potential curd firmness; kCF, the curd firming instant rate constant; and kSR, the syneresis instant rate constant) and maximum CF traits (MCF; comprising CFmax, the maximum CF value; and tmax, the time of attainment). Furthermore, we investigated 96 single nucleotide polymorphisms (SNPs) from 54 candidate genes, testing their associations with the above-listed traits. Milk and blood samples were collected from 1271 cows (each sampled once) from 85 herds. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model (including the effects of herd, days in milk, parity and additive polygenic effects) was used to estimate the genetic parameters of the studied traits. The same model with the addition of the SNP genotype effect was used for our association analysis. The heritability estimates of CFt and the MCF traits (RCTeq=0.258; kCF=0.230; CFmax=0.191; tmax=0.278) were similar to those obtained using traditional MCPs (0.187 to 0.267), except for the lower estimates for CFP (0.064) and kSR (0.077). A total of 13 of the 51 tested SNPs had relevant additive effects on at least one trait. We observed associations between MCPs and SNPs in the genes encoding ATP-binding cassette sub-family G member 2 (ABCG2), chemokine ligand 2 (CCL2), growth hormone 1 (GH1), prolactin (PRL) and toll-like receptor 2 (TLR2). Whereas, CFt and the MCF traits were associated with polymorphisms in the α-s1-casein (CSN1S1), β-casein (CSN2), GH1, oxidized low-density lipoprotein receptor 1 (OLR1), phospholipase C β1 (PLCB1), PRL and signal transducer and activator of transcription 5A (STAT5A) genes.

Recent progress has been achieved in the identification of quantitative trait loci (QTLs) and candidate genes, and they have been found to be very important for the production of chickens with more desirable meat characteristics. The major economic traits of chicken meat production were divided into two major categories, namely growth and carcass condition. In this paper, the QTL locations and candidate genes for the above mentioned traits are reviewed. The results presented here will provide guidelines for the selection of high quality and highly productive chickens through the marker assisted selection (MAS), which should be extensively used by poultry breeders and companies.

Crib-biting in horses is a stereotypic oral behaviour. Genetic susceptibility has been suggested on a causal basis, together with environmental factors such as stress, gastric discomfort and frustration caused by stall restrictions. This study aimed to test the associations of known or suspected stereotypic genes with equine crib-biting, including Ghrelin, Ghrelin receptor, Leptin, Dopamine receptor, μ-opioid receptor, N-cadherin, Serotonin receptor and Semaphorin. We conducted a candidate gene study with a case–control design, including 98 crib-biting and 135 control horses of two breeds, Finnhorses and half-breds. Detailed phenotypic information on crib-biting behaviour was surveyed through an owner-completed questionnaire. Control horses were more than 10 years old and without a history of crib-biting. Single nucleotide polymorphisms flanking the candidate genes were genotyped using either Sanger sequencing or Taqman assays. According to the survey, the affected horses started crib-biting at a young age, had exhibited crib-biting for more than a year, and expressed the behaviour after feeding or when stressed. Comparison of allele frequencies between the cases and controls for each breed separately did not provide evidence of an association at any of the tested loci. These results suggest that the previously known stereotypic genes are not major risk factors for crib-biting in horses, and further genome-wide studies are warranted on larger sample cohorts.

The biggest threat to the war on malaria is the continued evolution of drug resistance by the parasite. Resistance to almost all currently available antimalarials now exists in Plasmodium falciparum which causes the most suffering among all human malaria parasites. Monitoring of antimalarial efficacy and the development and subsequent spread of resistance has become an important part in the treatment and control of malaria. With recent reports of reduced efficacy of artemisinin, the current recommended treatment for uncomplicated malaria, there is urgent need for better methods to recognize and monitor drug resistance for effective treatment. Molecular markers have become a welcome addition to complement the more laborious and costly in vitro and in vivo methods that have traditionally been used to monitor drug resistance. However, there are currently no molecular markers for resistance to some antimalarials. This review highlights the role of the various genetic and genomic approaches that have been used in identifying the molecular markers that underlie drug resistance in P. falciparum. These approaches include; candidate genes, genetic linkage and genome-wide association studies. We discuss the requirements and limitations of each approach and use various examples to illustrate their contributions in identifying genomic regions of the parasite associated with antimalarial drug responses.

Decline in fertility of high-producing dairy cattle has become a global challenge to the dairy industry. Because of low heritability and complexity, it is difficult to find genetic markers for fertility traits in cattle. Here, we report the use of an in vitro fertilization (IVF) system and candidate gene approach to test genetic associations of a single-nucleotide polymorphism (SNP) in bovine placental lactogen (bPL), and its interactions with SNPs in the prolactin receptor (PRLR) and growth hormone receptor genes with fertility traits in an IVF system. The associations suggest a possible involvement of genetic interactions between bPL and PRLR in the fertilization and embryonic development processes, and the potential for application in a marker-assisted selection program.

There is substantial evidence that host genetic factors play a major role in determining the outcome of infection with many pathogens. Detailed analysis of malaria has identified twelve genes that affect susceptibility in various human populations. However, less attention has been paid to other major infectious diseases where twin studies have identified an important host genetic component to susceptibility. Recent progress in the analysis of the human genome offers exciting prospects for the mapping and identification of new susceptibility and resistance genes for common infectious diseases. Screening of the whole genome in affected sibling pair studies is now feasible by employing highly informative microsatellite markers. In addition, many polymorphic candidate genes have become available for analysis in case-control studies. It is proposed that these new genetic tools offer a powerful approach to the epidemiological analysis of many infectious diseases in humans and supersede traditional genetic approaches to identifying susceptibility genes in mouse models. Progress in characterizing the role of major histocompatibility genes in susceptibility to malaria and other infectious diseases is reviewed before outlining the methodologies for and progress in identifying non-MHC susceptibility genes.

White-feathered broilers dominate world poultry meat production owing to their rapid growth and high feed efficiency. However, consumers' preference for colourfeathered and slow-growing meat-type quality chickens is growing in certain regions of the world. Among them, the ‘Three Yellow’ of China and ‘Label Rouge’ in France are two famous examples. The appearance (plumage, skin, combs and so on), meat flavour, and meat texture are the main attributes that attract customers to purchase them. For practical breeding, quality chickens were initially produced by direct use of native chicken breeds, which are generally slowly-growing with poor feed conversion. Currently, the breeding for quality chickens in China is characterized with crossbreeding between native breeds and highly-selected lines with rapid growth rate or relatively high egg production. The breeding objectives focus on improving growth rate and reproductive efficiency while maintaining original appearance characters of native chicken such as plumage colour, body shape, comb shape, skin and shank colour and so on. The performances of native chickens have been greatly improved by crossbreeding. Two-way or three-way crossing is commonly used in producing commercial quality chickens in China. In some cases, the dw gene has been introduced into maternal line for better reproduction efficiency and lower feed cost. For future development, breeders and producers will place more and more breeding significance on meat quality traits, which include meat flavour, tenderness, fat deposition, muscle fibre composition, visual characters and so on. As evaluation of these traits is expensive and time-consuming, new molecular markers will play more important roles. Once reliable markers are identified, early marker assisted selection can be performed with great selection accuracy and without slaughtering. Attempts to identify candidate genes related to meat flavour, muscle fibre, lipid metabolism and other physical characters have brought great potentials for future breeding of quality chickens.