One of the domesticated species; the dog has been selectively bred for various aims by human. The dog has many breeds, which are artificially selected for specific behaviors and morphologies. Dogs contribute their life to human as working dogs for guide, rescue, detection or etc. Working dogs requires good personality, such as gentleness, robustness and patience for performing their special duty. Many studies have concentrated on finding genetic marker for selecting the high-quality working dog. In this study, we confirmed quantitative expression patterns of eight genes (
ABAT
; 4-Aminobutyrate Aminotransferase,
PLCB1
; Phospholipase C, Beta 1,
SLC10A4
; Solute Carrier Family 10, Member 4,
WNT1
; Wingless-Type MMTV Integration Site Family, Member 1,
BARX2
; BarH-Like Homeobox 2,
NEUROD6
; Neuronal Differentiation 6, SEPT9; Septin 9 and
TBR1
; T-Box, Brain, 1) among brains tissues from four dog breeds (Beagle, Sapsaree, Shepherd and Jindo), because these genes were expressed and have functions in brain mostly. Specially,
BARX2
,
SEPT9
,
SLC10A4
,
TBR1
and
WNT1
genes were highly expressed in Beagle and Jindo, and Sapsaree and German Shepherd were vice versa. The biological significance of total genes was estimated by database for annotation, visualization and integrated discovery (DAVID) to determine a different gene ontology (GO) class. In these analyses, we suppose to these eight genes could provide influential information for brain development, and intelligence of organisms. Taken together, these results could provide clues to discover biomarker related to functional traits in brain, and beneficial for selecting superior working dogs.
Introduction
The dog (
Canis lupus familiaris
) had been domesticated from wild gray wolves (
Canis lupus
). Based on archeological data, the dogs had had first artificial selection that from 100,000 to 15,000 years ago in multiple locations, including Europe, the Middle East and East Asia
[48
,
49]
. Nowadays, the dog population is separated into more than 400 breeds exist in worldwide
[36]
. The dogs evolved through a mutually valuable relationship with human beings, and their abilities have been developed to perform an outstanding variety of working or special roles. These roles include military watch, security guards, shepherds, guides, rescue and pets
[45]
. Working dogs are required to good personality of gentleness, robustness and patience for performing their special duty. Several animal personality are influenced by the activity of specific genes
[17
,
42]
. Specially, the brain specific genes controls behavior, personality, or aggression, therefore it is needed to study for confirming the gene expression patterns in brain. Microarray studies have been performed to assess changes in behavior with gene expression patterns in the brain
[46]
. We tried to identify such expression changes of eight genes in brain of four domesticated dog breeds (Beagle, German Shepherd, Sapsaree and Jindo), then compared to their expression patterns.
A major goal in the brain and behavioral sciences is to identify genes that influence social behavior and understand how their gene products influence the structure and function of the nervous system
[17
,
42
,
46]
. Thus, the aim of this study was to predict the relationships among personality traits (calmness, trainability, dog sociability, boldness, and etc.) of dogs. Gene expression profiles may reflect the complete personality of regulatory pathways; therefore we describe the gene expression patterns of eight genes (
ABAT, BARX2, NEUROD6, SEPT9, SLC10A4, PLCB1, TBR1, WNT1
) in dog breeds.
The domestic dogs display an extraordinary level of phenotypic diversity in personality and behavior, because dog breeding was introduced as various methods by human during the nineteenth century
[48
,
50]
. As the results of artificial selection, each dog breeds have fixed phenotypic traits
[12
,
47]
. In this point, it is important to select the suitable traits of special dog from many dog breeds. In this study, we presented each gene expression patterns in four dog breeds, which provides the clue to study of each dog breeds of specific traits.
The Beagle is one breed of small to medium-sized dog, and developed primarily for tracking wild animals as detection dogs. Their great sense of smell and tracking ability is used to detect food items, drug, or explosive detection
[6]
. Due to their strength, intelligence, trainability and obedience, German Shepherds are generally used in search-and-rescue, police, or military dogs around the world. German Shepherds have abilities of tracking, patrolling, or detection by training
[39]
. Therefore, the German Shepherd is the widely used breeds for military, police or scent-work roles.
As the Korean traditional breeds, Sapsaree is known as dauntlessness and loyalty aspects. Jindo is also one of the Korean traditional breeds, and well known for its unwavering loyalty and gentle nature. Because the Sapsaree and Jindo are an active and intelligent dog, it requires frequent interaction with people or another dog in the family
[14
,
28]
. Although they are frequently used as pet dog or guide dog, they are not frequently used as special dogs. In order to use these breeds as special dogs, gene expression patterns in brain could be good clues.
Materials and Methods
- Tissue samples, RNA isolation and synthesis of cDNA
One post-mortem brain tissue sample was extracted from four dog breeds (Beagle, German Shepherd, Sapsaree, and Jindo). Beagle and Sapsaree brain tissues were obtained by Chungnam National University with approval by the Animal Ethics Committee (CNU-00199). German Shepherd and Jindo brain tissues by Rural Development Administration (Jeonju, Korea), and the animals received care in accordance with the standard guidelines for the Care and Use of Laboratory Animals provided by the National Institute of Animal Science Animal Care Committee, and the experiment was executed with approval from the animal ethics committee under the operation rule of animal experiment ethics at the National Institute of Animal Science (approval number: 2014-085).
Cellular RNA of dog brain tissues was isolated by TRIzol® Reagent (Invitrogen, Carlsbad, CA, USA) to purify total RNA according to the manufacturer’s guidelines. After RNA isolation, the quality and quantity of the resulting single-stranded RNAs were assessed using a ND-1000 spectrophotometer (NanoDrop, Wilmington, DE, USA). Total RNA was treated and reverse-transcribed using a Prime-Script RT reagent kit with genomic DNA Eraser (Takara Bio, Shiga, Japan) according to the instructions of the manufacturer. Eight pairs of primer were designed to detect the mRNA of each gene according to the open reading frames (ORFs) in the whole genome (
Table 1
)
Gene description and the information of primers used in this study for real-time RT-PCR analysis
Gene description and the information of primers used in this study for real-time RT-PCR analysis
- Quantitative real time RT-PCR amplification
Quantitative real-time RT-PCR was performed with the Rotor-Gene Q system (QIAGEN, Hilden, Germany) with a gene-specific primer set (
Table 1
). Each of amplification reaction mixture (20 μl) contained 7 μl of H
2
O, 10 μl of QuantiTech SYBR Green PCR Master Mix (QIAGEN, Hilden, NW, Germany), 1 μl each of forward and reverse primers at 10 nmol/ μl, and 1 μl of cDNA template. In addition, to confirm non-specific background amplification, we amplified a template control without cDNA. Real-time RT-PCR amplifications for target genes and housekeeping genes were conducted as follows: 30 cycles each of 95℃ for 15 s, annealing temperature for 15 s, and 72℃ for 15 s. Annealing temperature range is set from 54 to 57℃ depends on genes. Melting curve analysis was performed for 30 s at 65-99℃. To guarantee reproducibility, we amplified all samples in triplicate and the results were averaged. As a standard control, we used
GAPDH
(Glyceraldehyde-3-phosphate dehydrogenase) in gene expression, for normalization of real-time RT-PCR amplification.
- Gene ontology analysis and functional annotations
Functional annotation of eight genes was analyzed by the DAVID (Database for Annotation, Visualization and integrated Discovery)
[16]
. DAVID calculates
P
-values to demonstrate GO terms enrichment, where P-values less than 0.05 are considered to be strongly enriched in the annotation category after Benjamini multiple test correction. We then performed gene ontology (GO) term analyses and each genes were grouped as GO terms. The results of significant GO terms were queried to the REViGO program in order to construct a scatterplot and interactive graph
[44]
, and then we summarized GO terms on the 2D semantic space by semantic similarities.
P
-values were originated from the Benjamini and Hochberg false discovery rate (FDR), and the color of circles indicates enriched GO terms with FDR <0.05.
Results and Discussion
- Gene expression patterns in four breeds
Our gene expression data indicate that similar expression patterns were presented in four breeds of dog. Generally, Beagle and Jindo are dominant expressed patterns, whereas German shepherd and Sapsaree are lower expressed than Beagle and Jindo (
Fig. 1
).
Quantitative real-time RT-PCR analysis is performed for the comparison of eight genes (ABAT, BARX2, NEUROD6, SEPT9, SLC10A4, PLCB1, TBR1, WNT1) of expression levels in four dog breeds. The tanscript copy number of eight genes were normalized to GAPDH housekeeping gene copy number in each sample. The values and their error bars indicate means, and standard deviation (n=3).
ABAT has several psychiatry roles, and regulate specially gamma-aminobutyric acid (GABA) in neuronal cells by catalyzing the degradation of GABA. Thus low-expressed ABAT gene induces to enhanced amount of GABA in the synaptic junctions, then increases GABA-mediated signaling by means of the GABA receptors
[26]
. Specially, GABA has no means to penetrate the blood-brain barrier, so it must be synthesized in the brain. Therefore to elucidate
ABAT
expression patterns in the brain is important for neuronal processes and brain development
[51]
. In the brain of four dog breeds,
ABAT
is high-expressed in Beagle, and low-expressed in Shepherd. The two breeds of Sapsaree and Jindo, originated from Korea, have similar expression patterns.
BARX2, SLC10A4, TBR1
and
WNT1
genes have same expression patterns.
BARX2
gene is known as transcription factor of cell adhesion
[33]
. The mechanisms of cell adhesion is very important for brain morphology, and functions such as learning, signal transduction, and memory
[40]
. When the early development of the nervous system, neurons maintain synapses by formation of cell-cell adhesions. Differently expressed patterns could provide the formation of brain cell, and the features of personality or intelligence. TBR1 has a role in glutamatergic projection in neuron differentiation. Glutamatergic neurons express receptors for the excitatory neurotransmitter glutamate as opposed to receptors for the inhibitory neurotransmitter GABA
[23]
. Solute carriers (SLCs) have a role for the transmembrane transport of various materials, such as amino acids, sugars, or inorganic ions. SLC10A4, one of the solute carrier family, has a role of carrying solution in blood or body fluid.
SLC10A1
genes were involved in blood-brain barrier
[19]
, and SLC10A4 also has possible important roles in brain. Therefore, the problems of SLC in the brain could induce mental illness such as ADHD, depression or psychiatric disorders
[38]
. The study of this gene in the dog could help to elucidate the canine mental illness or behavior disorders.
Proto-oncogene protein WNT1, has been originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. Joubert syndrome is a rare genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination
[31
,
32]
. Wnt signaling pathway controlled by WNT1, is stimulated by BDNF (Brain-derived neurotrophic factor), then induce the proliferation and differentiation of neural stem cells
[13]
. These genes same expression patterns have crucial roles in brain, and each gene pathway studies will be performed as further studies.
Three genes,
NEUROD6, SEPT9
and
PLCB1
, were similar expressed patterns and highest expressed in Beagle. NEUROD6 is transcription factors, and associated to differentiation or development of the nervous system. It also regulates fasciculation and targeted axogenesis in the neocortex
[8]
. SEPT9 (septin 9) is involved in cytokinesis and cell cycle control, and known as a candidate for the ovarian tumor suppressor gene [
20
]. Mutations in this gene cause hereditary neuralgic amyotrophy
[30]
, and a chromosomal translocation involving this gene on chromosome 17 and the
MLL
gene on chromosome 11 results in acute myelomonocytic leukemia
[29]
. SEPT9 is highest expressed in Beagle, but we could not detect to specific expression patterns. SEPT9 is related to not only neural diseases but also diseases such as leukemia or tumor, therefore the specific expression patterns is need to be specified.
PLCB1 catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate by using calcium as a cofactor
[21]
. This reaction plays an important role in the intracellular transduction of many extracellular signals.
The general features of total eight genes in the organisms were listed, and these genes have crucial roles for cellular metabolisms, DNA binding, or cell signaling (
Table 2
). The variable gene expression patterns in four breeds of dog brain can provide clues for the studies of breed-specific traits.
The function of each genes used in this study
The function of each genes used in this study
- Function prediction of eight genes
A GO analysis was performed in order to confirm the biological function of the eight genes. The gene set was confirmed as cellular GO terms, such as cell differentiation, multicellular organismal process, and cellular developmental process. The full list of statistically significant GO terms is enumerated (
Table 3
). Total 12 functions were enriched, and the most significant function is cell differentiation (
P
-value = 0.038) with four genes. Multicellular organismal process includes six of eight genes, except SLC10A4 and PLCB1 genes. BARX2, TBR1, and WNT1 genes were enriched in positive regulation of various biological processes, such as DNA-dependent transcription, RNA metabolic process, and nucleic acid metabolic process. Interestingly, these two genes were high-expressed in Beagle and Jindo, whereas low-expressed in Shepherd and Sapsaree. According to these facts, we summarized that positive regulation of biological process is enhanced in the brain of two breeds, Beagle and Jindo.
The function of eight genes based on GO term analysis
The function of eight genes based on GO term analysis
We used the REViGO program to get the functional relationship of GO terms in the network structure. The scatter plots and integrated graph show the cell metabolism-related GO terms, including cell differentiation, multicellular organismal process, cellular developmental process, and positive regulation of transcription, DNA-template (
Fig. 2
). WNT1 gene is included in all GO terms, and crucial factor of each network structure. WNT1 regulate the wnt signaling pathway, then induce neural stem cell differentiation
[13]
. Therefore,
WNT1
gene can provide a clue for the study of wnt signaling brain cell, and their mental features. SEPT9 gene is also included in the scatter plots and integrated graph. SEPT9 gene is related to cell division, such as cell cytokinesis and cell cycle
[20]
. SEPT9 is also high-expressed in human lymphoid and malignant brain tumors
[43]
. We predict to these genes can provide crucial information for brain development, and intelligence of organisms.
Molecular functions of eight genes in this study. After DAVID analysis, GO terms were obtained (P-values <0.05). Each GO terms of eight genes were queried to the REViGO program. (A) Scatter plots of GO terms from eight genes are viewered, and circles indicated by color depict significantly enriched GO terms with FDR <0.05. (B) Integrated graph of biological process from eight genes is presented by integrating nodes. Each GO terms (FDR <0.05) of each biological process were depicted in the 2D semantic space as default options from a REViGO. The circle size of each GO terms is relative to statistical significance, and edge thickness depicts between two nodes.
In conclusion, we selected eight genes related to brain functions, then confirmed their expression patterns, functions, and network. Total genes have a similar expression patterns, and their function is related to cell differentiation, cellular developmental process and multicellular organismal process. This data provides the fundamental clues for the studies of brain functions.
Acknowledgements
This research was supported by awards from the AGENDA project (Project No. PJ009254) in the National Institute of Animal Science, Rural Development Administration (RDA).
Abe T.
,
Kanemitu Y.
,
Nakasone M.
,
Kawahata I.
,
Yamakuni T.
,
Nakajima A.
,
Suzuki N.
,
Nishikawa M.
,
Hishinuma T.
,
Tomioka Y.
2013
SLC10A4 is a protease-activated transporter that transports bile acids
J. Biochem
mvt031
Bartholomä A.
,
Nave K. A.
1994
NEX-1: a novel brain-specific helix-loop-helix protein with autoregulation and sustained expression in mature cortical neurons
Mech. Dev.
48
217 -
228
DOI : 10.1016/0925-4773(94)90061-2
Baxter K. K.
,
Uittenbogaard M.
,
Yoon J.
,
Chiaramello A.
2009
The neurogenic basic helix-loop-helix transcription factor NeuroD6 concomitantly increases mitochondrial mass and regulates cytoskeletal organization in the early stages of neuronal differentiation
ASN Neuro
1
195 -
211
DOI : 10.1042/AN20090036
Berstein G.
,
Blank J. L.
,
Jhon D. Y.
,
Exton J. H.
,
Rhee S. G.
,
Ross E. M.
1992
Phospholipase C-β1 is a GTPase-activating protein for G q/11, its physiologic regulator
Cell
70
411 -
418
DOI : 10.1016/0092-8674(92)90165-9
Biase D.
,
Barra D.
,
Simmaco M.
,
John R. A.
,
Bossa F.
1995
Primary Structure and Tissue Distribution of Human 4 Aminobutyrate Aminotransferase
Eur. J. Biochem
227
476 -
480
DOI : 10.1111/j.1432-1033.1995.tb20412.x
Bielfelt S.
,
Redman H.
,
McClellan R.
1971
Sire-and sex-related differences in rates of epileptiform seizures in a purebred beagle dog colony
Am. J. Vet. Res.
32
2039 -
2048
Bormuth I.
,
Yan K.
,
Yonemasu T.
,
Gummert M.
,
Zhang M.
,
Wichert S.
,
Grishina O.
,
Pieper A.
,
Zhang W.
,
Goebbels S.
,
Tarabykin V.
,
Nave K. A.
,
Schwab M. H.
2013
Neuronal basic helix-loop-helix proteins Neurod2/6 regulate cortical commissure formation before midline interactions
J. Neurosci.
33
641 -
651
DOI : 10.1523/JNEUROSCI.0899-12.2013
Brault V.
,
Moore R.
,
Kutsch S.
,
Ishibashi M.
,
Rowitch D. H.
,
McMahon A. P.
,
Sommer L.
,
Boussadia O.
,
Kemler R.
2001
Inactivation of the (β)-catenin gene by Wnt1-Cremediated deletion results in dramatic brain malformation and failure of craniofacial development
Development
128
1253 -
1264
Bulfone A.
,
Smiga S. M.
,
Shimamura K.
,
Peterson A.
,
Puelles L.
,
Rubenstein J. L.
1995
T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex
Neuron
15
63 -
78
DOI : 10.1016/0896-6273(95)90065-9
Caricasole A.
,
Sala C.
,
Roncarati R.
,
Formenti E.
,
Terstappen G. C.
2000
Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLCβ1)
Biochim. Biophys. Acta
1517
63 -
72
DOI : 10.1016/S0167-4781(00)00260-8
Chase K.
,
Jones P.
,
Martin A.
,
Ostrander E. A.
,
Lark K. G.
2009
Genetic mapping of fixed phenotypes: disease frequency as a breed characteristic
J. Hered
100
S37 -
S41
DOI : 10.1093/jhered/esp011
Chen B. Y.
,
Wang X.
,
Wang Z. Y.
,
Wang Y. Z.
,
Chen L. W.
,
Luo Z. J.
2013
Brain derived neurotrophic factor stimulates proliferation and differentiation of neural stem cells, possibly by triggering the Wnt/β catenin signaling pathway
J. Neurosci. Res.
91
30 -
41
Cho G.
2005
Microsatellite polymorphism and genetic relationship in dog breeds in Korea
Asian Australas. J. Anim. Sci.
18
1071 -
1074
DOI : 10.5713/ajas.2005.1071
da Silva T. C.
,
Polli J. E.
,
Swaan P. W.
2013
The solute carrier family 10 (SLC10): beyond bile acid transport
Mol. Aspects Med.
34
252 -
269
DOI : 10.1016/j.mam.2012.07.004
Dennis G.
,
Sherman B. T.
,
Hosack D. A.
,
Yang J.
,
Gao W.
,
Lane H. C.
,
Lempicki R. A.
2003
DAVID: database for annotation, visualization, and integrated discovery
Genome Biol.
4
3 -
DOI : 10.1186/gb-2003-4-5-p3
Dingemanse N. J.
,
Kazem A. J.
,
Réale D.
,
Wright J.
2010
Behavioural reaction norms: animal personality meets individual plasticity
Trends Ecol. Evol.
25
81 -
89
DOI : 10.1016/j.tree.2009.07.013
Fortress A. M.
,
Schram S. L.
,
Tuscher J. J.
,
Frick K. M.
2013
Canonical Wnt signaling is necessary for object recognition memory consolidation
J. Neurosci.
33
12619 -
12626
DOI : 10.1523/JNEUROSCI.0659-13.2013
Geier E. G.
,
Chen E. C.
,
Webb A.
,
Papp A. C.
,
Yee S. W.
,
Sadee W.
,
Giacomini K. M.
2013
Profiling Solute Carrier Transporters in the Human Blood–Brain Barrier
Clin. Pharmacol. Ther.
94
636 -
639
DOI : 10.1038/clpt.2013.175
Hall P. A.
,
Jung K.
,
Hillan K. J.
,
Russell S.
2005
Expression profiling the human septin gene family
J. Pathol.
206
269 -
278
DOI : 10.1002/path.1789
Han J. Y.
,
Shin E. S.
,
Lee Y.
,
Ghang H.
,
Kim S.
,
Hwang J.
,
Kim J.
,
Lee J.
2013
A genome-wide association study for irinotecan-related severe toxicities in patients with advanced non-small-cell lung cancer
Pharmacogenomics J.
13
417 -
422
DOI : 10.1038/tpj.2012.24
Hevner R. F.
,
Miyashita-Lin E.
,
Rubenstein J. L.
2002
Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: evidence that cortical and thalamic axons interact and guide each other
J. Comp. Neurol.
447
8 -
17
DOI : 10.1002/cne.10219
Hevner R. F.
,
Shi L.
,
Justice N.
,
Hsueh Y.
,
Sheng M.
,
Smiga S.
,
Bulfone A.
,
Goffinet A. M.
,
Campagnoni A. T.
,
Rubenstein J. L.
2001
Tbr1 regulates differentiation of the preplate and layer 6
Neuron
29
353 -
366
DOI : 10.1016/S0896-6273(01)00211-2
Jirholt J.
,
Asling B.
,
Hammond P.
,
Davidson G.
,
Knutsson M.
,
Walentinsson A.
,
Jensen J. M.
,
Lehmann A.
,
Agreus L.
,
Lagerstrom-Fermer M.
2011
4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease
PLoS One
6
e19095 -
DOI : 10.1371/journal.pone.0019095
Jung M.
,
Lippert B.
,
Metcalf B.
,
Böhlen P.
,
Schechter P.
1977
γ-Vinyl GABA (4-amino-hex-5-enoic acid), a new selective irreversible inhibitor of GABA-T: Effects on brain GABA metabolism in mice
J. Neurochem.
29
797 -
802
DOI : 10.1111/j.1471-4159.1977.tb10721.x
Kay J. N.
,
Voinescu P. E.
,
Chu M. W.
,
Sanes J. R.
2011
Neurod6 expression defines new retinal amacrine cell subtypes and regulates their fate
Nat. Neurosci.
14
965 -
972
DOI : 10.1038/nn.2859
Kim K.
,
Tanabe Y.
,
Park C.
,
Ha J.
2001
Genetic variability in East Asian dogs using microsatellite loci analysis
J. Hered.
92
398 -
403
DOI : 10.1093/jhered/92.5.398
Kreuziger L. M. B.
,
Porcher J. C.
,
Ketterling R. P.
,
Steensma D. P.
2007
An MLL-SEPT9 fusion and t (11; 17)(q23; q25) associated with de novo myelodysplastic syndrome
Leuk. Res.
31
1145 -
1148
DOI : 10.1016/j.leukres.2006.12.006
Kuhlenbäumer G.
,
Hannibal M. C.
,
Nelis E.
,
Schirmacher A.
,
Verpoorten N.
,
Meuleman J.
,
Watts G. D.
,
De Vriendt E.
,
Young P.
,
Stögbauer F.
2005
Mutations in SEPT9 cause hereditary neuralgic amyotrophy
Nat. Genet.
37
1044 -
1046
DOI : 10.1038/ng1649
Lancaster M. A.
,
Gopal D. J.
,
Kim J.
,
Saleem S. N.
,
Silhavy J. L.
,
Louie C. M.
,
Thacker B. E.
,
Williams Y.
,
Zaki M. S.
,
Gleeson J. G.
2011
Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome
Nat. Med.
17
726 -
731
DOI : 10.1038/nm.2380
Louie C. M.
,
Gleeson J. G.
2005
Genetic basis of Joubert syndrome and related disorders of cerebellar development
Hum. Mol. Genet.
14
R235 -
R242
DOI : 10.1093/hmg/ddi264
Meech R.
,
Edelman D. B.
,
Jones F. S.
,
Makarenkova H. P.
2005
The homeobox transcription factor Barx2 regulates chondrogenesis during limb development
Development
132
2135 -
2146
DOI : 10.1242/dev.01811
Nagata K. I.
,
Asano T.
,
Nozawa Y.
,
Inagaki M.
2004
Biochemical and cell biological analyses of a mammalian septin complex, Sept7/9b/11
J. Biol. Chem.
279
55895 -
55904
DOI : 10.1074/jbc.M406153200
Osei Y. D.
,
Churchich J. E.
1995
Screening and sequence determination of a cDNA encoding the human brain 4-aminobutyrate aminotransferase
Gene
155
185 -
187
DOI : 10.1016/0378-1119(94)00858-P
Parker H. G.
,
Kim L. V.
,
Sutter N. B.
,
Carlson S.
,
Lorentzen T. D.
,
Malek T. B.
,
Johnson G. S.
,
DeFrance H. B.
,
Ostrander E. A.
,
Kruglyak L.
2004
Genetic structure of the purebred domestic dog
Science
304
1160 -
1164
DOI : 10.1126/science.1097406
Peruzzi D.
,
Aluigi M.
,
Manzoli L.
,
Billi A. M.
,
Di Giorgio F. P.
,
Morleo M.
,
Martelli A. M.
,
Cocco L.
2002
Molecular characterization of the human PLC beta1 gene
Biochim. Biophys. Acta
1584
46 -
54
DOI : 10.1016/S1388-1981(02)00269-X
Rask-Andersen M.
,
Masuram S.
,
Fredriksson R.
,
Schiöth H. B.
2013
Solute carriers as drug targets: current use, clinical trials and prospective
Mol. Aspects Med.
34
702 -
710
DOI : 10.1016/j.mam.2012.07.015
Ruefenacht S.
,
Gebhardt-Henrich S.
,
Miyake T.
,
Gaillard C.
2002
A behaviour test on German Shepherd dogs: heritability of seven different traits
Appl. Anim. Behav. Sci.
79
113 -
132
DOI : 10.1016/S0168-1591(02)00134-X
Sakisaka T.
,
Takai Y.
2005
Cell adhesion molecules in the CNS
J. Cell Sci.
118
5407 -
5410
DOI : 10.1242/jcs.02672
Sander G.
,
Bawden C. S.
,
Hynd P. I.
,
Nesci A.
,
Rogers G.
,
Powell B. C.
2000
Expression of the homeobox gene, Barx2, in wool follicle development
J. Invest. Dermatol.
115
753 -
756
DOI : 10.1046/j.1523-1747.2000.00122.x
Storlazzi C.
,
Brekke H.
,
Mandahl N.
,
Brosjö O.
,
Smeland S.
,
Lothe R.
,
Mertens F.
2006
Identification of a novel amplicon at distal 17q containing the BIRC5/SURVIVIN gene in malignant peripheral nerve sheath tumours
J. Pathol.
209
492 -
500
DOI : 10.1002/path.1998
Supek F.
,
Bošnjak M.
,
Škunca N.
,
Šmuc T.
2011
REVIGO summarizes and visualizes long lists of gene ontology terms
PLoS One
6
e21800 -
DOI : 10.1371/journal.pone.0021800
Toth A. L.
,
Varala K.
,
Newman T. C.
,
Miguez F. E.
,
Hutchison S. K.
,
Willoughby D. A.
,
Simons J. F.
,
Egholm M.
,
Hunt J. H.
,
Hudson M. E.
2007
Wasp gene expression supports an evolutionary link between maternal behavior and eusociality
Science
318
441 -
444
DOI : 10.1126/science.1146647
Vaysse A.
,
Ratnakumar A.
,
Derrien T.
,
Axelsson E.
,
Rosengren Pielberg G.
,
Sigurdsson S.
,
Fall T.
,
Seppala E. H.
,
Hansen M.
,
Lawley C. T.
2011
Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping
PLoS Genet.
7
e1002316 -
DOI : 10.1371/journal.pgen.1002316
Vila C.
,
Savolainen P.
,
Maldonado J. E.
,
Amorim I. R.
,
Rice J. E.
,
Honeycutt R. L.
,
Crandall K. A.
,
Lundeberg J.
,
Wayne R. K.
1997
Multiple and ancient origins of the domestic dog
Science
276
1687 -
1689
DOI : 10.1126/science.276.5319.1687
Wayne R. K.
,
Geffen E.
,
Girman D. J.
,
Koepfli K. P.
,
Lau L. M.
,
Marshall C. R.
1997
Molecular systematics of the Canidae
Syst. Biol.
46
622 -
653
DOI : 10.1093/sysbio/46.4.622