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The monoamine oxidase A (MAOA) gene is an important candidate gene for human behavior that encodes an enzyme regulating the metabolism of key neurotransmitters. The regulatory mechanisms of the MAOA gene in dogs are yet to be elucidated. We measured MAOA gene transcription and analyzed the VNTR genotype and methylation status of the gene promoter region in different dog breeds to determine whether MAOA expression is correlated with the MAOA genotype or epigenetic modification in dogs. We found brain-specific expression of the MAOA gene and different transcription levels in different dog breeds including Beagle, Sapsaree, and German shepherd, and also a robust association of the DNA methylation of the gene promoter with mRNA levels. However, the 90 bp tandem repeats that we observed near the transcription start site were not variable, indicating no correlation with canine MAOA activity. These results show that differential DNA methylation in the MAOA promoter region may affect gene expression by modulating promoter activity. Moreover, the distinctive patterns of MAOA expression and DNA methylation may be involved in breed-specific or individual behavioral characteristics, such as aggression, because behavioral phenotypes are related to different physiological and neuroendocrine responses.

Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethylated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.

Mobile genetic elements within genomes have been known to drive genome evolution in diverse ways. Since developing high-technology for whole-genome sequencing, many researchers have focused on not only how mobile genetic elements have affected the evolution of genes and their function, particularly of human and mammals, but also how these elements involve in gene activation or inactivation associated with a number of human diseases. Here we describe what kind of biological changes by mobile genetic elements contribute to disease, especially cancer and present an overview of what is known about this large, and largely unexplored, segment of the genome. Finally, we discuss understanding the genomic changes or cellular responses to genotoxic stress such as radiation may permit to implicate for potential clinical application.

Transposable elements (TEs) have skill of altering the position inside the genome and these TEs are widespread in both of plants and animals. They are separated into class I called retrotransposons, and class II called DNA transposons. According to the previous studies, not only TEs are related with disease, they are key factor of human and primate evolution. From this review, we discussed about the impact of transposable element, its role in the genome of human and primates and how TE distribution is differ from them. Additionally, we described how TEs contributed on primate evolution by its unique role. This review could be great use for further studies in relation to evolution mechanism and various diseases.

Although humans and canines exhibit similar behavioral features, it is not easy to identify the corresponding behavioral phenotypes. The variable number of tandem repeats (VNTR) in intron 4 of the tyrosine hydroxylase (TH) gene is related to two characteristics, namely, impulsive activity and inattention. The TH genes are defined by three genotypes: type 1/1 comprises a single copy of TH VNTR; type 1/2 is heterozygote for both short allele and long allele; and type 2/2 is the doubled form of TH VNTR, which leads to inattention and impulsive actions. The 1/1 and 1/2 genotype have been identified as biomarkers for concentration and impulsive action. Therefore, we performed PCR amplification to detect the 1/2 genotypes in three canine breeds from Korea: Sapsaree (49), Poongsan (18), and Jindo (20). Our results indicate that the Sapsaree dog carries 27 % of the 2/2 genotype, 59 % of the 1/2 genotype, and 14 % of the 1/1 genotype; the Poongsan dog carries 11 % of the 2/2 genotype, 22 % of 1/2 genotype, and 67 % of 1/1 genotype; whereas the Jindo dog carries 10 % of the 2/2 genotype, 40 % of the 1/2 genotype, and 50 % of the 1/1 genotype. Taken together, our data indicate that the Jindo, Poongsan, and Sapsaree dogs harbor decreasing amounts of phenotypes responsible for inattention and impulsive behavior, in that order. Additionally, the Sapsaree genes harbor higher amounts of the 1/2 genotype than the Jindo and Poongsan genes, respectively.

There are more than 400 pure dog breeds developed through intentional artificial selection and purebred breeding. Purebred animals have higher risk of inbreeding depression and hereditary diseases. We investigated the genetic diversity and structure of three dog breeds in South Korea by using 12 microsatellite loci for one Korean native dog breed, Sapsaree, and two foreign breeds, German shepherd and Belgian Malinois. The mean allele number of nine loci across all dog breeds was 4.833, and the number of alleles per locus ranged from 2 to 8. The mean of expected and observed heterozygosity were 0.415 and 0.577, respectively. Sapsaree, Korean native dog, had higher level of genetic diversity than the foreign German shepherd and Belgian Malinois. The highest mean value of polymorphism information content was found in Sapsaree (0.480), followed by Belgian Malinois (0.373) and German shepherd (0.355). Pairwise genetic differentiation was estimated using fixation index F ST. Sapsaree and German shepherd (F ST = 0.2536) and Sapsaree and Belgian Malinois (F ST = 0.2522) had very great genetic differentiation, while moderate level of genetic differentiation was observed between German shepherd and Belgian Malinois (F ST = 0.1003). These genetic information and structure of the three dog breeds will be effective in conservation and preservation of the genetic diversity of the three dog breeds.

Physical exercise induces gene expression changes that trigger glucose metabolism pathways in organisms. In the present study, we monitored the expression levels of LDHA (lactate dehydrogenase) and GYS1 (glycogen synthase 1) in the blood, to confirm the roles of these genes in exercise physiology. LDHA and GYS1 are related to glucose metabolism and fatigue recovery, and these processes could elicit economically important traits in racehorses. We collected blood samples from three retired thoroughbred racehorses, pre-exercise and immediately after 30 min of exercise. We extracted total RNA and small RNA (≤ 200 nucleotide-long) from the blood, and assessed the expression levels of LDHA, GYS1, and microRNAs (miRNAs), by using qRT-PCR. We showed that LDHA and GYS1 were down-regulated, whereas eca-miR-33a and miR-17 were up-regulated, after exercise. We used sequences from the 3′ UTR of LDHA and GYS1, containing eca-miR-33a and miR-17 binding sites, to observe the down-regulation activity of each gene expression. We observed that the two miRNAs, namely, eca-miR-33a and miR-17, inhibited LDHA and GYS1 expression via binding to the 3′ UTR sequences of each gene. Our results indicate that eca-miR-33a and miR-17 play important roles in the glucose metabolism pathway. In addition, our findings provide a basis for further investigation of the exercise metabolism of racehorses.

The endogenous retrovirus (ERV) appeared in the vertebrate genome millions of years ago, but is now inactivated due to mutations such as deletions or nonsense mutations. After the mutation, ERV eventually became fixed in the genome in its endogenous form. In the case of human ERV (HERV), 98 000 ERV elements or fragments were inserted into the human genome, which is approximately 8% of the whole genome.1 HERV is defective and unable to replicate and only traces of the original viruses exist in the human genome.2 Even though HERVs have been reported to be inactive, there are several studies showing the relationship between HERVs and some diseases including cancers. Contreras-Galindo et al 3 first showed that HERV-K genes are significantly upregulated in the plasma of lymphoma and breast cancer patients and that there are virus-like particles in the plasma of lymphoma patients. Many other studies have shown that HERV-K can be a good model for immunotherapeutic targets4 and is a biomarker of early-stage breast cancer.5 Additionally, there have been reports demonstrating that HERV-K is involved in breast cancer,4–⇓6 prostate cancer,7 melanoma8 and ovarian cancer.9 ERV3-1 (HERV-R) is related to lymphoma10 and HERV-E is upregulated in urothelial carcinoma11 and colon cancer.12 We recently reported that the ERV3-1 (HERV-R) env protein is expressed in both adult human organs and tumours using a tissue microarray. We also compared the expression of ERV3-1 between normal and tumour tissues to study the relationship between ERV3-1 and tumour formation. ERV3-1 was highly expressed in certain types of tumours, including lung adenocarcinoma, renal cell carcinoma, papillary carcinoma, hepatocellular carcinoma and adenocarcinoma in the gastrointestinal tract.13 Although …

Alzheimer's disease (AD) is the most common form of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. The ε4 allele of the apolipoprotein E (APOE) gene has been recognized as a major genetic risk factor for the more common, complex, late-onset AD. Fibrillar deposits by phosphorylated tau are also a key pathological feature of AD. The retromer complex also has been reported to late-onset AD. More recently, genome-wide association studies (GWASs) identified putative novel candidate genes associated with late-onset AD. Lastly, several studies showed that circulating microRNAs (miRNAs) in the cerebrospinal fluid (CSF) and blood serum of AD patients can be used as biomarkers in AD diagnosis. This review addresses the advances and challenges in determining genetic and diagnostic markers for complex AD pathogenesis.

Human endogenous retroviruses (HERV) env proteins have been recently reported to be significantly up-regulated in certain cancers. Specifically, mRNA and protein levels of HERV-K (HML-2) are up-regulated in the blood plasma or serum of breast cancer patients. Here, we collected blood samples of 49 breast cancer patients and analyzed mRNA expressions of various HERVs env genes including HERV-R, HERV-H, HERV-K, and HERV-P by real-time PCR. The expression of env genes were significantly increased in the blood of primary breast cancer patients but were decreased in patients undergoing chemotherapy to a similar level with benign patients. When we compared the group currently undergoing chemotherapy and those patients undergoing chemotherapy simultaneously with radiotherapy, HERVs env genes were reduced more in the chemotherapy only group, suggesting that chemotherapy is more effective in reducing HERV env gene expression than is radiotherapy. Among chemotherapy groups, HERV env gene expression was the lowest in the taxotere- or taxol-treated group, suggesting that taxotere and taxol can reduce HERVs env expression. These data suggest the potential to use HERVs env genes as a diagnosis marker for primary breast cancer, and further studies are needed to identify the mechanism and physiological significance of the reduction of HERV env gene expression during chemotherapy.

Working dogs serve as military watch dogs, search dogs, rescue dogs, and guide dogs with un-come-at-able character. They are drafted by in-training examination including concentration, capacity for locomotion, boldness and earthly desires. In this study, genetic diversity and relationships among two groups of working dogs (pass and fail group in-training examination) were assessed based on 15 microsatellite markers in 25 individuals of working dogs (military watch dogs and Korean search dogs). For the 15 microsatellite markers, the values of allelic richness (AR) ranged from 2.21 (pass group) to 1.60 (fail group) in military watch dogs, while AR ranged from 2.79 (pass group) to 2.72 (fail group) in Korean search dogs. Among 52 different alleles of military watch dogs, 22 alleles were detected in pass group only, while 8 alleles in fail group only. In case of Korean search dogs, 3 alleles were observed in pass group only, while 13 alleles in fail group only. These group-specific unique alleles reflect good biomarker for selecting working dogs (military watch dogs and Korean search dogs), indicating that those group specific microsatellite alleles could separate working dogs to be pass or fail group in out-training dog population. Taken together, this study demonstrates the feasibility of microsatellite analyses for the selection of superior working dogs objectively. Furthermore, this approach could be used for the proper selection of working dogs in combination with in-training examination.

Canine and human behavior are shaped by similar evolutionary processes, yet the identification of the behavioral phenotype is often difficult. A widely used method relies on breed stereotypes provided by experts such as dog trainers. To reveal a valid association between behavior and genetic factors, an association study of behavioral phenotyping and genotyping is essential. We screened for variable number of tandem repeat (VNTR) polymorphisms in intron 4 of the tyrosine hydroxylase gene in military working dogs (belonging to pass and fail groups based on the results of an in-training examination conducted by the drillmaster), which were scored based on possessiveness, audaciousness, concentration, and motor ability by qualification examination. We first characterized each genotype by sequencing, in which the 1/1 type consists of a single copy of a 36-bp sequence and the 2/2 type is a duplicated form of the 36-bp repeat unit. The 1/2 alleles showed a single nucleotide change as a heteroduplex, which generated a PCR product of similar size as that of the 1/1-182-bp. The military working dogs showed the 2/2 type of VNTR and heteroduplex. For the pass group, two dogs possessed 2/2 type (40 %), whereas three dogs were of the heteroduplex type (60 %). However, all members of fail group showed the 2/2 type (100 %). These data indicate that repeat polymorphisms with behavioral phenotyping can identify military working dogs that would pass or fail the in-training examination.

Genetic variations of functional genes in various animal species have been previously examined to understand the relationship between genotypes and phenotypes. Repeat polymorphism can be found in not only coding sequences but also untranslated regions of the protein-coding genes, affecting gene regulation via a variety of mechanisms. In this respect, repeat polymorphisms including microsatellites, variable number of tandem repeats (VNTRs), and short interspersed nuclear elements (SINEs) in relation to functional genes contribute to recognition of genetic or phenotypic variation and individual identification. These elements are biologically valuable markers for studies on association between genetic make-up and behavioral patterns in dog breeds. Hence, to examine the effect of genotype on behavior, studies on this combination are certainly important. Hence, this review could cast light on the functional roles of repeat polymorphisms in dog behavior and breed variation.

Endogenous retroviruses (ERVs), which are footprints of ancient germline infections, were inserted into the genome during the early stages of primate evolution. Human endogenous retroviruses (HERVs) occupy approximately 8% of the human genome. Although most ERV genes are defective, with large deletions, stop codons, and frameshifts in their open reading frames (ORFs), some full-length sequences containing long ORFs are expressed in several tissues and cancers. Several envelope glycoproteins that are encoded by env genes have retained some characteristics of their ancestral infectious viruses. These glycoproteins play essential physiological roles in the organs in which they are expressed. Previous studies have demonstrated the expression of ERV env at the mRNA level in cells and tissues rather than at the protein level, which is more difficult to detect. However, it is not known whether Env is functionally conserved in primates. To understand the possible role of Env in primates, we examined the expression of the env genes of four ERVs (ERV-R, -K, -W, and -FRD) at the protein as well as mRNA levels in various tissues of the rhesus monkey. The ERV env gene products were observed at moderate to high levels in each tissue that was examined and showed tissue-specific expression patterns. Our data suggest a biologically important role for retroviral proteins in healthy tissues of the rhesus monkey.

Background DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. Results We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density. Conclusions We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.

SINE-VNTR-Alu (SVA) elements are present in hominoid primates and are divided into 6 subfamilies (SVA-A to SVA-F) and active in the human population. Using a bioinformatic tool, 22 SVA element-associated genes are identified in the human genome. In an analysis of genomic structure, SVA elements are detected in the 5' untranslated region (UTR) of HGSNAT (SVA-B), MRGPRX3 (SVA-D), HYAL1 (SVA-F), TCHH (SVA-F), and ATXN2L (SVA-F) genes, while some elements are observed in the 3'UTR of SPICE1 (SVA-B), TDRKH (SVA-C), GOSR1 (SVA-D), BBS5 (SVA-D), NEK5 (SVA-D), ABHD2 (SVA-F), C1QTNF7 (SVA-F), ORC6L (SVA-F), TMEM69 (SVA-F), and CCDC137 (SVA-F) genes. They could contribute to exon extension or supplying poly A signals. LEPR (SVA-C), ALOX5 (SVA-D), PDS5B (SVA-D), and ABCA10 (SVA-F) genes also showed alternative transcripts by SVA exonization events. Dominant expression of HYAL1_SVA appeared in lung tissues, while HYAL1_noSVA showed ubiquitous expression in various human tissues. Expression of both transcripts (TDRKH_SVA and TDRKH_noSVA) of the TDRKH gene appeared to be ubiquitous. Taken together, these data suggest that SVA elements cause transcript isoforms that contribute to modulation of gene regulation in various human tissues.