Genome‐wide association study identifies energy metabolism genes for resistance to ketosis in Chinese Holstein cattle

Ketosis (KET) is one common metabolic disorder that occurs mainly in early lactation and affects the dairy industry with significant economic losses. Cows with ketosis have lower milk yield and reproductive performance and greater risk of other periparturient diseases. As a metabolic disease, the pathogenesis of KET is multifactorial. To better understand the genetic background of KET, a genome‐wide association study was performed using the Illumina BovineSNP50 BeadChip. Single‐step genomic BLUP methodology was used to incorporate genomic data into a threshold‐liability model. Results of the GWAS are reported as the proportion of variance explained by 20‐SNP windows. Six genomic regions on Bos taurus autosomes 10, 13, 14 and 25 showed association with KET. Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy‐metabolism‐associated genes to the genetic basis of KET. Our results provide new information about the underlying biology and molecular mechanisms associated with KET. Future studies that combine genomic variation analysis and functional gene information may help elucidate the biology of KET.     

Leptospiral glycolipoprotein as a candidate antigen for serodiagnosis of human leptospirosis

Aims:  Development of a simple, specific, rapid and inexpensive Dot-ELISA test for early diagnosis of human leptospirosis.
Methods and Results:  Serum samples from 90 patients diagnosed with leptospirosis were analysed by Dot-ELISA test incorporating Glycolipoprotein (GLP) antigen from serovars Copenhageni and Patoc. Results were compared with those obtained with microscopic agglutination test, currently, the gold standard reference serological method. Serum samples from healthy blood bank donors and patients diagnosed with diseases other than leptospirosis were used as negative controls. The specificities of both GLP-based assays were 97·1% and 100% with serum samples from patients with other diseases and with serum samples from healthy control group, respectively. With serum samples from patients with acute leptospirosis, sensitivity was 76·6% with Dot-ELISA Copenhageni and 90·0% with Dot-ELISA Patoc. With serum samples from patients in convalescence, sensitivity was 100% with both GLP-based assays.
Conclusions:  This Dot-ELISA provides a candidate antigen for serodiagnosis of leptospirosis during all phases of illness and could be a good alternative method for the early diagnosis of leptospirosis.
Significance and Impact of the Study:  The Dot-ELISA test is simple, specific, rapid and inexpensive. It is suitable for identifying a large number of samples and, hence, reducing the death rate of patients with leptospirosis.     

Screening for signatures of selection of Tianzhu white yak using genome‐wide re‐sequencing

The Tianzhu white yak, a domestic yak indigenous to the Qilian Mountains, migrated inland from the Qinghai‐Tibet Plateau. Specific ecological and long‐term artificial selection influenced the evolution of its pure white coat and physiological characteristics. Therefore, it is not only a natural population that represents a genomic selective region of environmental adaptability but is also an animal model for studying the pigmentation of the yak coat. A total of 24 261 829 variants, including 22 445 252 SNPs, were obtained from 29 yaks by genome‐wide re‐sequencing. According to the results of a selective sweep analysis of Tianzhu white yak in comparison to Tibetan yaks, nine candidate genes under selection in Tianzhu white yak were identified by combining π, Tajima's D, πA/πB and F_ST statistics, with threshold standards of 5%. These genes include PDCD1, NUP210, ABCG8, NEU4, LOC102287650, D2HGDH, COL4A1, RTP5 and HDAC11. Five of the nine genes were classified into 12 molecular signaling pathways, and most of these signaling pathways are involved in environmental information processing, organismal systems and metabolism. A majority of these genes has not been implicated in previous studies of yak coat color and high‐altitude animals. Our findings are helpful not only for explaining the molecular mechanism of yak coat pigmentation but also for exploring the genetic changes in Tianzhu white yak due to environmental adaptation.     

Linking genotypes to phenotypes and fitness: how mechanistic biology can inform molecular ecology

The accessibility of new genomic resources, high‐throughput molecular technologies and analytical approaches such as genome scans have made finding genes contributing to fitness variation in natural populations an increasingly feasible task. Once candidate genes are identified, we argue that it is necessary to take a mechanistic approach and work up through the levels of biological organization to fully understand the impacts of genetic variation at these candidate genes. We demonstrate how this approach provides testable hypotheses about the causal links among levels of biological organization, and assists in designing relevant experiments to test the effects of genetic variation on phenotype, whole‐organism performance capabilities and fitness. We review some of the research programs that have incorporated mechanistic approaches when examining naturally occurring genetic and phenotypic variation and use these examples to highlight the value of developing a comprehensive understanding of the relationship between genotype and fitness. We give suggestions to guide future research aimed at uncovering and understanding the genetic basis of adaptation and argue that further integration of mechanistic approaches will help molecular ecologists better understand the evolution of natural populations.     

Evaluation of results from genome‐wide studies of language and reading in a novel independent dataset

Recent genome‐wide association scans (GWAS) for reading and language abilities have pin‐pointed promising new candidate loci. However, the potential contributions of these loci remain to be validated. In this study, we tested 17 of the most significantly associated single nucleotide polymorphisms (SNPs) from these GWAS studies (P < 10^?6 in the original studies) in a new independent population dataset from the Netherlands: known as Familial Influences on Literacy Abilities. This dataset comprised 483 children from 307 nuclear families and 505 adults (including parents of participating children), and provided adequate statistical power to detect the effects that were previously reported. The following measures of reading and language performance were collected: word reading fluency, nonword reading fluency, phonological awareness and rapid automatized naming. Two SNPs (rs12636438 and rs7187223) were associated with performance in multivariate and univariate testing, but these did not remain significant after correction for multiple testing. Another SNP (rs482700) was only nominally associated in the multivariate test. For the rest of the SNPs, we did not find supportive evidence of association. The findings may reflect differences between our study and the previous investigations with respect to the language of testing, the exact tests used and the recruitment criteria. Alternatively, most of the prior reported associations may have been false positives. A larger scale GWAS meta‐analysis than those previously performed will likely be required to obtain robust insights into the genomic architecture underlying reading and language.     

Proteomic Analysis of Haptoglobin and Amyloid A Protein Levels in Patients with Vivax Malaria

Advancements in the field of proteomics have provided great opportunities for the development of diagnostic and therapeutic tools against human diseases. In this study, we analyzed haptoglobin and amyloid A protein levels of vivax malaria patients with combinations of depletion of the abundant plasma proteins, 2-dimensional gel electrophoresis (2-DE), image analysis, and mass spectrometry in the plasma between normal healthy donors and vivax malaria patients. The results showed that the expression level of haptoglobin had become significantly lower or undetectable in the plasma of vivax malaria patients due to proteolytic cleavage when compared to healthy donors on 2-DE gels. Meanwhile, serum amyloid A protein was significantly increased in vivax malaria patient''s plasma with high statistical values. These 2 proteins are common acute phase reactants and further large scale evaluation with a larger number of patient''s will be necessary to establish the possible clinical meaning of the existential changes of these proteins in vivax malaria patients. However, our proteomic analysis suggests the feasible values of some plasma proteins, such as haptoglobin and serum amyloid A, as associating factor candidates for vivax malaria.