Genome-wide association study revealed genomic regions related to white/red earlobe color trait in the Rhode Island Red chickens
- Changsheng Nie†1,
- Zebin Zhang†1,
- Jiangxia Zheng†1,
- Hongyan Sun2,
- Zhonghua Ning1,
- Guiyun Xu1,
- Ning Yang1 and
- Lujiang Qu1Email author
© The Author(s). 2016
Received: 22 February 2016
Accepted: 28 July 2016
Published: 5 August 2016
Earlobe color is a naturally and artificially selected trait in chicken. As a head furnishing trait, it has been selected as a breed characteristic. Research has demonstrated that white/red earlobe color was related to at least three loci and sex-linked. However, there has been little work to date to identify the specific genomic regions and genes response to earlobe color in Rhode Island Red chickens. Currently, it is possible to identify the genomic regions responsible for white/red earlobe in Rhode Island Red chicken to eliminate this gap in knowledge by using genome-wide association (GWA) analysis.
In the present study, genome-wide association (GWA) analysis was conducted to explore the candidate genomic regions response to chicken earlobe color phenotype. Hens with red dominant and white dominant earlobe was used for case-control analysis by Illumina 600 K SNP arrays. The GWA results showed that 2.38 Mb genomic region (50.13 to 52.51 Mb) with 282 SNPs on chromosome Z were significantly correlated to earlobe color, including sixteen known genes and seven anonymous genes. The sixteen genes were PAM, SLCO4C1, ST8SIA4, FAM174A, CHD1, RGMB, RIOK2, LIX1, LNPEP, SHB, RNF38, TRIM14, NANS, CLTA, GNE, and CPLX1.
The study has revealed the white/red earlobe trait is polygenic and sex-linked in Rhode Island Red chickens. In the genome significant ~2.38 Mb region, twenty-three genes were found and some of them could play critical roles in the formation of white/red earlobe color, especially gene SLCO4C1. Taken together, the candidate genes findings herein can help elucidate the genomic architecture of response to white/red earlobe and provide a new insight on mechanisms underlying earlobe color in Rhode Island Red chickens and other breeds.
KeywordsRhode Island Red chicken Earlobe color GWAS
Earlobe color, a qualitative trait in chicken, is artificially and naturally selected in various breeds [1, 2]. It is a part of skin structure on the face without feathers and below the ear. In nature, shining color is selected to get more attention of their predators or partners [3, 4]. Earlobe color, a head furnishing trait, has been selected as a breed characteristic. Red or white earlobes are predominant in a number of the wild and domestic chickens worldwide  although yellow, blue, purple and black earlobe could be found in some breeds.
Variation in chicken earlobe color may be caused by ancestral lineages and mutations , as well as the adaptability to local conditions . For example, The presence of white earlobes is due to purine base deposition and the formation of other color earlobe is attributed to the mixture of different pigments including melanin or carotenoid . The red earlobe, the same color as the rest of the red face, could reflect the health of the birds with the degree of redness .
Genetic foundation studies of chicken earlobe color were conducted in previous studies. The white earlobe has been identified to be polygenic and it appeared to be sex-linked in some breeds . The mottled earlobe in Rhode Island Reds appears to be produced by two recessive autosomal genes . Recently, Wragg et al.  identified 7 concordant significances (P < 0.05 and Z > 4) SNPs on chicken chromosomes 1, 2, 4 and Z related to white/red earlobe color by using genome-wide association (GWA) analysis, indicating that earlobe color trait is sex-linked and polygenic. However, there has been little work to date to identify the accurate genomic regions and genes response to earlobe color in Rhode Island Red chickens. To eliminate this gap in knowledge, we performed a genome-wide association study (GWAS) to identify the genomic regions responsible for white/red earlobe in the Rhode Island Red chickens.
After quality control, a total of 78 female chickens aged 20 weeks old were analyzed, of which 48 (61 %) presented white earlobe color as cases and 30 (39 %) presented red earlobe color as controls. The MultiDimensional scaling (MDS) analysis indicated the absence of population stratification in our study population (Additional file 1: Figure S1).
Summary description of genes in ~2.38 Mb region on chromosome Z
Peptidylglycine alpha-amidating monooxygenase
50,043,929 - 50,172,820
Solute carrier organic anion transporter family member 4C1
Transport estrone 3-sulfate .
ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4
Modulator of the adhesive properties of neural cell adhesion molecule .
Family with sequence similarity 174 member A
Chromodomain helicase DNA binding protein 1
Repulsive guidance molecule family member b
RIO kinase 2
Limb and CNS expressed 1
Src homology 2 domain containing adaptor protein B
Ring finger protein 38
Tripartite motif containing 14
A mediator in the immune response against viral infection .
N-acetylneuraminic acid synthase
Change expression in response to androgen .
Clathrin light chain A
Additionally, a total of four autosomal regions with 6 SNPs were suggestive significantly related to white/red earlobe in chicken (1.95 × 10−5) (Fig. 1 and Additional file 4: Table S2), of which two on chromosome 2 (one with 2 SNPs and the other one with 1 isolated SNP) (67.19 Mb ~ 67.21 Mb), one on chromosome 5 (1 isolated SNP), and one on chromosome 7 (2 SNPs) (10.09 Mb ~ 10.12 Mb).
The aims of this study were to identify and estimate the genomic regions responsible for white/red earlobe in Rhode Island Red chickens, and to locate positional candidate genes association with color earlobe by using a 600 K SNP panel for genotyping. In a brief, a total of 282 genome significantly SNP markers on chromosome Z were detected in this study, which corresponded to sixteen known genes and seven anonymous genes.
Gene SLCO4C1 (solute carrier organic anion transporter family member 4C1) was identified for earlobe color within an average of 101 kb of twenty-five the genome-wide significant SNPs (Additional file 2: Table S1). This plausible positional candidate gene, SLCO4C1, may have its special function in earlobe color formation as it is among numerous significant SNPs that in linkage disequilibrium (LD) building up to a QTL peak.
Candidate gene, SLCO4C1, belongs to the organic anion transporting polypeptide (OATP) family. Researchers have demonstrated that OATP family had the function of transportation of the amphipathic organic compounds, like bile salt in mammals [10, 11]. The component of bile salt, biliverdin, can be deposited to form blue eggshell . Wang et al.  reported in chicken SLCO1B3 was in response to blue eggshell color formation via transferring biliverdin. Although the molecule transfer mechanism of earlobe color formation remains unknown, earlobes color was occurred due to purine base deposition or mixture of different pigments . In practical, breeders believed some relations exist between earlobe and eggshell color, which might be caused by the close association of the determining genes on the chromosome or single factor that controls the pigmentation of both egg and earlobe .
Thus, based on the current results, pigments deposition to form earlobe color, as well as the relations between earlobe and eggshell color, it is reasonable for us to speculate SLCO4C1 may play an important role in the formation of earlobe color. Future validation of this assumption of SLCO4C1 gene function is warranted in chicken.
Besides the crucial positional candidate gene SLCO4C1, other candidate genes located in this ~2.38 Mb region have various functions (Table 1). For example, RNF38, CHD1, PAM, RGMB, LNPEP, RNF38, TRIM14 and GNE were detected to be associated with diseases [12–15]. ST8SIA4, PAM, RIOK2, LNPEP, LIX1, SHB, TRIM14 and GNE have been discovered to be important in regulating the life process [16–20]. NANS can change expression in response to androgen. CPLX1 and RIOK2 were correlated with cytoplasmic maturation  or synaptic vesicle exocytosis . CLTA was found associated with cytoplasmic face of coated pits  and vesicles progress . Currently, the mechanism underlying earlobe color is almost unknown and few literatures support these candidate genes were directly in response to earlobe color. However, the GWAS results in this study may provide a clue for researcher to identify the relationship between these candidate genes and earlobe color. Further validation experiment of these genes was needed to perform.
Compared to our findings, Wragg et al.  has found 7 SNPs significantly associated with white/red earlobe color in various breeds via GWAS. In the study of Wragg et al., two SNPs (rs14170217 and rs14170463) were located on chromosome 2 at region 41.69 Mb and 41.89 Mb, respectively , which were ~25.5 Mb and ~25.3 Mb, respectively, downstream of our suggestive significantly SNPs (rs315420052 and rs313803643). The SNPs, rs14170217 and rs14170463, in Wragg et al. study were in the intron of genes, ATP2C1 and MRPL3, respectively. In our study, both rs315420052 and rs313803643 were in the intron of gene GMDS. Another SNP, rs14762712, on chromosome Z at 32.08 Mb in Wragg et al. study  was also in intron in BNC2 that important to pigment pattern formation. In summary, all detected significant SNPs in Wragg et al. study were in the intron area of genes. Only BNC2 was more related to earlobe color, which is not found in our study.
Several reasons made the different results between ours and Wragg et al. study. Firstly, Wragg et al. use traditional breeds, Kenyan, Ethiopian, and Chilean village chickens to perform association analysis. Secondly, the phenotypic traits in Wragg et al. study were not only earlobe but yellow skin, oocyan, rose comb, and duplex comb. Thirdly, the experimental population birds almost have been post-prune in earlobe color in Wragg’s study. Moreover, compared to Wragg’s materials, our inbreeding population has a different phenotype in earlobe (Additional file 5: Figure S3) but a consistent genetic background, which is a good choice to perform GWAS. Also, GWAS always show different results in different populations . Taken together, it is not surprise to obtain different results from ours and Wragg et al. study. However, both Wragg et al. and our study showed polygenic and sex-linked inheritance pattern determined earlobe color although different breeds were used in different studies.
This study has revealed 282 genome significantly SNPs spanning ~2.38 Mb region on chromosome Z associated with earlobe color in Rhode Island Red chickens, corresponding to twenty-three genes. The genomic regions that we identified contain twenty-three genes with functions that suggest a role in response to earlobe color and, thus, these genes are both positional and functional candidates. Notably, among these twenty-three genes, SLCO4C1 may play critical roles in the formation of white/red earlobe color. Taken together, the candidate genes findings herein can help elucidate the genomic architecture of response to white/red earlobe and provide a new insight on mechanisms underlying earlobe color in Rhode Island Red chickens and other breeds.
Animals and phenotypic data
Genotyping and quality control
Genomic DNA was extracted by standard phenol/chloroform method and genotyped with 600 K Affymetrix Axiom Chicken Genotyping Array (Affymetrix, Inc. Santa Clara, CA, USA). Affymetrix Power Tools v1.16.0 (APT) software was then used for quality control and genotype calling. Specifically, only samples with dish quality control (DQC) > 0.82 and call rate > 97 % were used for subsequent analysis. After sample quality control analysis, the mean concordance rate was 99.7 %.
The classical multidimensional scaling (MDS) analysis was used to detect population structure in PLINK v1.09 software . By computing identical by state (IBS) scores for unlinked SNPs with r2 < 0.2 and using multidimensional scaling, a total of 78 samples were identified to involve in further analysis. Projection onto the two multidimensional scaling axes is shown in Additional file 1: Figure S1.
SNPs were removed with a minor allele frequency < 5 % in all samples (n = 135,166), or a P value of deviation from HardyWeinberg equilibrium (PHWE) < 1 × 10−6 in controls (n = 444). Ultimately, a total of 78 individuals and 370,106 SNPs were kept for the following association analysis.
To test the association of each SNP with earlobe color, we used the basic case/control association analysis according to the manual of PLINK (v1.09). All qualified SNPs were subjected to the linkage disequilibrium via the −−indep-pairwise 25 5 0.2 commend (PLINK) to generate a pruned subset of 50,946 linkage equilibrium SNPs.
The Bonferroni adjustment is a widely used method for correcting multiple hypothesis testing. Given the correlation between SNPs in linkage disequilibrium, the traditional Bonferroni adjustment appears to be overly conservative which key assumption is that all tests are independent . Herein, the sum of independent blocks plus singleton markers was used to define the number of independent statistical tests [27, 28]. With this approach, 50,946 independent tests were suggested to determine the P value threshold. Hence, the genome-wide significant and suggestive P values were 9.81 × 10−7 (0.05/50946) and 1.95 × 10−5 (1/50946), respectively. The Manhattan plot of genome wide P values of association analysis was created by self-developed R programming codes. To further location candidate region that affect trait, we performed linkage disequilibrium (LD) analysis with genome significantly SNPs in Haploview software (v4.2) .
DQC, dish quality control; GWAS, genome-wide association study; HD, high density; IBS, Identical by state; MDS, MultiDimensional scaling analysis
We are grateful for the help of all members of the poultry team of the National Engineering Laboratory for Animal Breeding.
This work was funded in part by the earmarked fund for the Beijing Innovation Team of the Modern Agro-industry Technology Research System (CARSPSTP) and National Scientific Supporting Projects of China (2015BAD03B03).
Availability of data and materials
The original data sets supporting the results of this article are available. They are not public, but are able to be accessed by request for result verification only.
CN and ZZ performed the experiments and analyzed the data. JZ, LQ, ZN, GX, and NY conceived and designed the experiment. CN and LQ wrote the manuscript. HS revised the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
All procedures and protocols involving animals were conducted in accordance with the Guidelines for the Care and Use of Experimental Animals established by the Ministry of Agriculture of China (Beijing, China). All animal work was approved by the Animal Welfare Committee of China Agricultural University (Beijing, China) (Permit Number: XK622).
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Salces AJ, Yebron Jr MGN, Salces CB, Dominguez JMD. Phenotypic and genetic characteristics of Boholano genetic group of Philippine native chicken (Gallus gallus domesticus, L.). Phil J Vet Animal Sci. 2015;41(1):1-11.Google Scholar
- Cabarles Jr JC, Lambio AL, Vega SA, Capitan SS, Mendioro MS. Distinct morphological features of traditional chickens (Gallus gallus domesticus L.) in Western Visayas, Philippines. Animal Genet Resour. 2012;51:73–87.View ArticleGoogle Scholar
- Houde AE. Sex, color, and mate choice in guppies. Princeton: Princeton University Press; 1997.Google Scholar
- Endler JA, Houde AE. Geographic variation in female preferences for male traits in Poecilia reticulata. Evolution. 1995;49:456–68.View ArticleGoogle Scholar
- Duguma R. Phenotypic characterization of some indigenous chicken ecotypes of Ethiopia. Livestock Res Rural Dev. 2006;18(9):article 131.Google Scholar
- Smyth Jr JR. Genetics of plumage, skin and eye pigmentation in chickens. In: Developments in Animal and Veterinary Sciences (Netherlands) no 22. 1990.Google Scholar
- Warren DC. Inheritance of earlobe color in poultry. Genetics. 1928;13(6):470–87.PubMedPubMed CentralGoogle Scholar
- Hays FA. Inheritance of mottled earlobes and stubs in Rhode Island Reds. Am Naturalist. 1943;77:471–5.View ArticleGoogle Scholar
- Wragg D, Mwacharo JM, Alcalde JA, Hocking PM, Hanotte O. Analysis of genome-wide structure, diversity and fine mapping of Mendelian traits in traditional and village chickens. Heredity. 2012;109(1):6–18.View ArticlePubMedPubMed CentralGoogle Scholar
- Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, et al. Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004;101(10):3569–74.View ArticlePubMedPubMed CentralGoogle Scholar
- Ueno A, Masugi Y, Yamazaki K, Komuta M, Effendi K, Tanami Y, Tsujikawa H, Tanimoto A, Okuda S, Itano O, et al. OATP1B3 expression is strongly associated with Wnt/beta-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma. J Hepatol. 2014;61(5):1080–7.View ArticlePubMedGoogle Scholar
- Rodrigues LU, Rider L, Nieto C, Romero L, Karimpour-Fard A, Loda M, Lucia MS, Wu M, Shi L, Cimic A, et al. Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer. Cancer Res. 2015;75(6):1021–34.View ArticlePubMedPubMed CentralGoogle Scholar
- Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N, Sigurdsson A, Helgadottir HT, Johannsdottir H, Magnusson OT, Gudjonsson SA, et al. Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nat Genet. 2014;46(3):294–8.View ArticlePubMedGoogle Scholar
- Li J, Ye L, Sanders AJ, Jiang WG. Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling. J Cell Biochem. 2012;113(7):2523–31.View ArticlePubMedGoogle Scholar
- Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF, Minna JD. Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res. 2000;60(17):4894–906.PubMedGoogle Scholar
- Schreiber SC, Giehl K, Kastilan C, Hasel C, Muhlenhoff M, Adler G, Wedlich D, Menke A. Polysialylated NCAM represses E-cadherin-mediated cell-cell adhesion in pancreatic tumor cells. Gastroenterology. 2008;134(5):1555–66.View ArticlePubMedGoogle Scholar
- Handa S, Spradling TJ, Dempsey DR, Merkler DJ. Production of the catalytic core of human peptidylglycine alpha-hydroxylating monooxygenase (hPHMcc) in Escherichia coli. Protein Expr Purif. 2012;84(1):9–13.View ArticlePubMedPubMed CentralGoogle Scholar
- Zemp I, Wild T, O'Donohue MF, Wandrey F, Widmann B, Gleizes PE, Kutay U. Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2. J Cell Biol. 2009;185(7):1167–80.View ArticlePubMedPubMed CentralGoogle Scholar
- Moeller C, Yaylaoglu MB, Alvarez-Bolado G, Thaller C, Eichele G. Murine Lix1, a novel marker for substantia nigra, cortical layer 5, and hindbrain structures. Brain Res Gene Expr Patterns. 2002;1(3–4):199–203.View ArticlePubMedGoogle Scholar
- Cho A, Hayashi YK, Monma K, Oya Y, Noguchi S, Nonaka I, Nishino I. Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy). J Neurol Neurosurg Psychiatry. 2014;85(8):914–7.View ArticlePubMedGoogle Scholar
- Giraudo CG, Eng WS, Melia TJ, Rothman JE. A clamping mechanism involved in SNARE-dependent exocytosis. Science (New York). 2006;313(5787):676–80.View ArticleGoogle Scholar
- Medendorp K, Vreede L, van Groningen JJ, Hetterschijt L, Brugmans L, Jansen PA, van den Hurk WH, de Bruijn DR, van Kessel AG. The mitotic arrest deficient protein MAD2B interacts with the clathrin light chain A during mitosis. PLoS One. 2010;5(11):e15128.View ArticlePubMedPubMed CentralGoogle Scholar
- Hennenberg M, Miersch J, Rutz B, Strittmatter F, Waidelich R, Stief CG, Gratzke C. Noradrenaline induces binding of Clathrin light chain A to alpha1-adrenoceptors in the human prostate. Prostate. 2013;73(7):715–23.View ArticlePubMedGoogle Scholar
- Myles S, Davison D, Barrett J, Stoneking M, Timpson N. Worldwide population differentiation at disease-associated SNPs. BMC Med Genomics. 2008;1:22.View ArticlePubMedPubMed CentralGoogle Scholar
- Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75.View ArticlePubMedPubMed CentralGoogle Scholar
- Johnson RC, Nelson GW, Troyer JL, Lautenberger JA, Kessing BD, Winkler CA, O'Brien SJ. Accounting for multiple comparisons in a genome-wide association study (GWAS). BMC Genomics. 2010;11:724.View ArticlePubMedPubMed CentralGoogle Scholar
- Nicodemus KK, Liu W, Chase GA, Tsai YY, Fallin MD. Comparison of type I error for multiple test corrections in large single-nucleotide polymorphism studies using principal components versus haplotype blocking algorithms. BMC Genet. 2005;6 Suppl:S78.View ArticleGoogle Scholar
- Gu X, Feng C, Ma L, Song C, Wang Y, Da Y, Li H, Chen K, Ye S, Ge C, Gu X, Feng C, Ma L, Song C, Wang Y, Da Y, Li H, Chen K, Ye S, Ge C, et al. Genome-wide association study of body weight in chicken F2 resource population. PLoS One. 2011;6(7):e21872.View ArticlePubMedPubMed CentralGoogle Scholar
- Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics (Oxford). 2005;21(2):263–5.View ArticleGoogle Scholar
- Simpson PD, Eipper BA, Katz MJ, Gandara L, Wappner P, Fischer R, Hodson EJ, Ratcliffe PJ, Masson N. Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cells. J Biol Chem. 2015;290(41):24891–901.View ArticlePubMedPubMed CentralGoogle Scholar
- Yamaguchi H, Sugie M, Okada M, Mikkaichi T, Toyohara T, Abe T, Goto J, Hishinuma T, Shimada M, Mano N. Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1. Drug Metab Pharmacokinetics. 2010;25(3):314–17.View ArticleGoogle Scholar
- Blake KD, Prasad C. CHARGE syndrome. Orphanet J Rare Dis. 2006; 1.Google Scholar
- Burkhardt L, Fuchs S, Krohn A, Masser S, Mader M, Kluth M, Bachmann F, Huland H, Steuber T, Graefen M, et al. CHD1 is a 5q21 tumor suppressor required for ERG rearrangement in prostate cancer. Cancer Res. 2013;73(9):2795–805.View ArticlePubMedGoogle Scholar
- Rodgers MJ, Banks DJ, Bradley KA, Young JA. CHD1 and CHD2 are positive regulators of HIV-1 gene expression. Virol J. 2014;11:180.View ArticlePubMedPubMed CentralGoogle Scholar
- Sanders AJ, Ye L, Li J, Mason MD, Jiang WG. Tumour angiogenesis and repulsive guidance molecule b: a role in HGF- and BMP-7-mediated angiogenesis. Int J Oncol. 2014;45(3):1304–12.PubMedGoogle Scholar
- Liu T, Deng M, Li J, Tong X, Wei Q, Ye X. Phosphorylation of right open reading frame 2 (Rio2) protein kinase by polo-like kinase 1 regulates mitotic progression. J Biol Chem. 2011;286(42):36352–60.View ArticlePubMedPubMed CentralGoogle Scholar
- Mao Y, Kucuk B, Irvine KD. Drosophila lowfat, a novel modulator of Fat signaling. Development (Cambridge, England). 2009;136(19):3223–33.Google Scholar
- Nakada TA, Russell JA, Wellman H, Boyd JH, Nakada E, Thain KR, Thair SA, Hirasawa H, Oda S, Walley KR. Leucyl/cystinyl aminopeptidase gene variants in septic shock. Chest. 2011;139(5):1042–9.View ArticlePubMedGoogle Scholar
- Cheng H, Li Y, Zuo XB, Tang HY, Tang XF, Gao JP, Sheng YJ, Yin XY, Zhou FS, Zhang C, et al. Identification of a missense variant in LNPEP that confers psoriasis risk. J Investigative Dermatology. 2014;134(2):359–65.View ArticleGoogle Scholar
- Diakonova M, Gunter DR, Herrington J, Carter-Su C. SH2-Bbeta is a Rac-binding protein that regulates cell motility. J Biol Chem. 2002;277(12):10669–77.View ArticlePubMedGoogle Scholar
- Saldeen J, Kriz V, Agren N, Welsh M. SHB and angiogenic factors promote ES cell differentiation to insulin-producing cells. Biochem Biophys Res Commun. 2006;344(2):517–24.View ArticlePubMedGoogle Scholar
- Kim SK, Ro JY, Kemp BL, Lee JS, Kwon TJ, Fong KM, Sekido Y, Minna JD, Dong WK, Mao L. Identification of three distinct tumor suppressor loci on the short arm of chromosome 9 in small cell lung cancer. Cancer Res. 1997;57(3):400–3.PubMedGoogle Scholar
- Zhou Z, Jia X, Xue Q, Dou Z, Ma Y, Zhao Z, Jiang Z, He B, Jin Q, Wang J. TRIM14 is a mitochondrial adaptor that facilitates retinoic acid-inducible gene-I-like receptor-mediated innate immune response. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(2):E245–254.View ArticlePubMedGoogle Scholar
- Romanuik TL, Wang G, Holt RA, Jones SJM, Marra MA, Sadar MD. Identification of novel androgenresponsive genes by sequencing of LongSAGE libraries. BMC Genomics. 2009; 10.Google Scholar
- Nishino I, Carrillo-Carrasco N, Argov Z. GNE myopathy: current update and future therapy. Journal of neurology, neurosurgery, and psychiatry. 2015;86(4):385–92.View ArticlePubMedGoogle Scholar
- Hinderlich S, Weidemann W, Yardeni T, Horstkorte R, Huizing M. UDP-GlcNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis. Topics in current chemistry. 2015;366:97–137.View ArticlePubMedPubMed CentralGoogle Scholar
- Krishnakumar SS, Radoff DT, Kummel D, Giraudo CG, Li F, Khandan L, Baguley SW, Coleman J, Reinisch KM, Pincet F, et al. A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion. Nature structural & molecular biology. 2011;18(8):934–40.View ArticleGoogle Scholar
- Kummel D, Krishnakumar SS, Radoff DT, Li F, Giraudo CG, Pincet F, Rothman JE, Reinisch KM. Complexin cross-links prefusion SNAREs into a zigzag array. Nature structural & molecular biology. 2011;18(8):927–33.View ArticleGoogle Scholar