
摘要
The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10−8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10−3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.
关键词
Human;GWAS;images;gene regulation;European;face;genome-wide association study
授权许可
通讯作者
推荐引用方式
Ziyi Xiong,Gabriela Dankova,Laurence J Howe,Myoung Keun Lee,Pirro G Hysi,Markus A de Jong,Gu Zhu,Kaustubh Adhikari,Dan Li,Yi Li,Bo Pan,Eleanor Feingold,Mary L Marazita,John R Shaffer,Kerrie McAloney,Shu-Hua Xu,Li Jin,Sijia Wang,Femke MS de Vrij,Bas Lendemeijer,Stephen Richmond,Alexei Zhurov,Sarah Lewis,Gemma C Sharp,Lavinia Paternoster,Holly Thompson,Rolando Gonzalez-Jose,Maria Catira Bortolini,Samuel Canizales-Quinteros,Carla Gallo,Giovanni Poletti,Gabriel Bedoya,Francisco Rothhammer,André G Uitterlinden,M Arfan Ikram,Eppo Wolvius,Steven A Kushner,Tamar EC Nijsten,Robert-Jan TS Palstra,Stefan Boehringer,Sarah E Medland,Kun Tang,Andres Ruiz-Linares,Nicholas G Martin,Timothy D Spector,Evie Stergiakouli,Seth M Weinberg,Fan Liu,Manfred Kayser. Novel genetic loci affecting facial shape variation in humans. eLife ,Vol.8(2019)
您觉得这篇文章对您有帮助吗?
分享和收藏
参考文献
[1] | J Lonsdale, J Thomas, M Salvatore, R Phillips. et al.(2013). The Genotype-Tissue expression (GTEx) project. Nature Genetics.45:580-585. DOI: 10.6084/m9.figshare.10298396. |
[2] | A Hofman, S Darwish Murad, CM van Duijn, OH Franco. et al.(2013). The Rotterdam study: 2014 objectives and design update. European Journal of Epidemiology.28:889-926. DOI: 10.6084/m9.figshare.10298396. |
[3] | KU Ludwig, E Mangold, S Herms, S Nowak. et al.(2012). Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nature Genetics.44:968-971. DOI: 10.6084/m9.figshare.10298396. |
[4] | N Gunhanlar, G Shpak, M van der Kroeg, LA Gouty-Colomer. et al.(2018). A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Molecular Psychiatry.23:1336-1344. DOI: 10.6084/m9.figshare.10298396. |
[5] | E Mangold, KU Ludwig, S Birnbaum, C Baluardo. et al.(2010). Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate. Nature Genetics.42:24-26. DOI: 10.6084/m9.figshare.10298396. |
[6] | A Visconti, DL Duffy, F Liu, G Zhu. et al.(2018). Genome-wide association study in 176,678 europeans reveals genetic loci for tanning response to sun exposure. Nature Communications.9. DOI: 10.6084/m9.figshare.10298396. |
[7] | J Guo, X Mei, K Tang. (2013). Automatic landmark annotation and dense correspondence registration for 3D human facial images. BMC Bioinformatics.14. DOI: 10.6084/m9.figshare.10298396. |
[8] | KU Ludwig, AC Böhmer, J Bowes, M Nikolic. et al.(2017). Imputation of orofacial clefting data identifies novel risk loci and sheds light on the genetic background of cleft lip ± cleft palate and cleft palate only. Human Molecular Genetics.26:829-842. DOI: 10.6084/m9.figshare.10298396. |
[9] | SF Grant, K Wang, H Zhang, W Glaberson. et al.(2009). A genome-wide association study identifies a locus for nonsyndromic cleft lip with or without cleft palate on 8q24. The Journal of Pediatrics.155:909-913. DOI: 10.6084/m9.figshare.10298396. |
[10] | M Visser, RJ Palstra, M Kayser. (2014). Human skin color is influenced by an intergenic DNA polymorphism regulating transcription of the nearby BNC2 pigmentation gene. Human Molecular Genetics.23:5750-5762. DOI: 10.6084/m9.figshare.10298396. |
[11] | M Visser, M Kayser, RJ Palstra. (2012). HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Research.22:446-455. DOI: 10.6084/m9.figshare.10298396. |
[12] | EJ Leslie, JC Carlson, JR Shaffer, A Butali. et al.(2017). Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate. Human Genetics.136:275-286. DOI: 10.6084/m9.figshare.10298396. |
[13] | X Zhou, M Stephens. (2014). Efficient multivariate linear mixed model algorithms for genome-wide association studies. Nature Methods.11:407-409. DOI: 10.6084/m9.figshare.10298396. |
[14] | Y Field, EA Boyle, N Telis, Z Gao. et al.(2016). Detection of human adaptation during the past 2000 years. Science.354:760-764. DOI: 10.6084/m9.figshare.10298396. |
[15] | F Liu, F van der Lijn, C Schurmann, G Zhu. et al.(2012). A genome-wide association study identifies five loci influencing facial morphology in europeans. PLOS Genetics.8. DOI: 10.6084/m9.figshare.10298396. |
[16] | . (2011). Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nature Genetics.43:561-564. DOI: 10.6084/m9.figshare.10298396. |
[17] | A Fraser, C Macdonald-Wallis, K Tilling, A Boyd. et al.(2013). Cohort profile: the avon longitudinal study of parents and children: alspac mothers cohort. International Journal of Epidemiology.42:97-110. DOI: 10.6084/m9.figshare.10298396. |
[18] | J Li, L Ji. (2005). Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity.95:221-227. DOI: 10.6084/m9.figshare.10298396. |
[19] | J Golding, M Pembrey, R Jones. (2001). ALSPAC--the avon longitudinal Study of parents and children. I. study methodology. Paediatric and Perinatal Epidemiology.15:74-87. DOI: 10.6084/m9.figshare.10298396. |
[20] | AM Toma, A Zhurov, R Playle, E Ong. et al.(2009). Reproducibility of facial soft tissue landmarks on 3D laser-scanned facial images. Orthodontics & Craniofacial Research.12:33-42. DOI: 10.6084/m9.figshare.10298396. |
[21] | HA Thomason, MJ Dixon, J Dixon. (2008). Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and shh signaling. Developmental Biology.321:273-282. DOI: 10.6084/m9.figshare.10298396. |
[22] | YG Kamberov, S Wang, J Tan, P Gerbault. et al.(2013). Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell.152:691-702. DOI: 10.6084/m9.figshare.10298396. |
[23] | A Siepel, G Bejerano, JS Pedersen, AS Hinrichs. et al.(2005). Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research.15:1034-1050. DOI: 10.6084/m9.figshare.10298396. |
[24] | S Joss, U Kini, R Fisher, S Mundlos. et al.(2011). The face of ulnar mammary syndrome?. European Journal of Medical Genetics.54:301-305. DOI: 10.6084/m9.figshare.10298396. |
[25] | PG Hysi, AM Valdes, F Liu, NA Furlotte. et al.(2018). Genome-wide association meta-analysis of individuals of european ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability. Nature Genetics.50:652-656. DOI: 10.6084/m9.figshare.10298396. |
[26] | MK Singh, M Petry, B Haenig, B Lescher. et al.(2005). The T-box transcription factor Tbx15 is required for skeletal development. Mechanisms of Development.122:131-144. DOI: 10.6084/m9.figshare.10298396. |
[27] | J Tan, Y Yang, K Tang, PC Sabeti. et al.(2013). The adaptive variant EDARV370A is associated with straight hair in east asians. Human Genetics.132:1187-1191. DOI: 10.6084/m9.figshare.10298396. |
[28] | Y Sun, Y Huang, A Yin, Y Pan. et al.(2015). Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate. Nature Communications.6. DOI: 10.6084/m9.figshare.10298396. |
[29] | GR Abecasis, A Auton, LD Brooks, MA DePristo. et al.(2012). An integrated map of genetic variation from 1,092 human genomes. Nature.491:56-65. DOI: 10.6084/m9.figshare.10298396. |
[30] | K Adhikari, G Reales, AJ Smith, E Konka. et al.(2015). A genome-wide association study identifies multiple loci for variation in human ear morphology. Nature Communications.6. DOI: 10.6084/m9.figshare.10298396. |
[31] | CC Hui, AL Joyner. (1993). A mouse model of greig cephalo–polysyndactyly syndrome: the extra–toesJ mutation contains an intragenic deletion of the Gli3 gene. Nature Genetics.3:241-246. DOI: 10.6084/m9.figshare.10298396. |
[32] | KE Holsinger, BS Weir. (2009). Genetics in geographically structured populations: defining, estimating and interpreting F(ST). Nature Reviews Genetics.10:639-650. DOI: 10.6084/m9.figshare.10298396. |
[33] | BN Howie, P Donnelly, J Marchini. (2009). A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLOS Genetics.5. DOI: 10.6084/m9.figshare.10298396. |
[34] | W Satoh, M Matsuyama, H Takemura, S Aizawa. et al.(2008). Sfrp1, Sfrp2, and Sfrp5 regulate the wnt/beta-catenin and the planar cell polarity pathways during early trunk formation in mouse. Genesis.46:92-103. DOI: 10.6084/m9.figshare.10298396. |
[35] | GC Schwabe, B Trepczik, K Süring, N Brieske. et al.(2004). knockout mouse as a model for the developmental pathology of autosomal recessive robinow syndrome. Developmental Dynamics.229:400-410. DOI: 10.6084/m9.figshare.10298396. |
[36] | JR Shaffer, E Orlova, MK Lee, EJ Leslie. et al.(2016). Genome-Wide association study reveals multiple loci influencing normal human facial morphology. PLOS Genetics.12. DOI: 10.6084/m9.figshare.10298396. |
[37] | M Kayser, F Liu, AC Janssens, F Rivadeneira. et al.(2008). Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. The American Journal of Human Genetics.82:411-423. DOI: 10.6084/m9.figshare.10298396. |
[38] | MA de Jong, A Wollstein, C Ruff, D Dunaway. et al.(2016). An automatic 3D facial landmarking algorithm using 2D gabor wavelets. IEEE Transactions on Image Processing.25:580-588. DOI: 10.6084/m9.figshare.10298396. |
[39] | CH Kau, A Zhurov, R Scheer, S Bouwman. et al.(2004). The feasibility of measuring three-dimensional facial morphology in children. Orthodontics and Craniofacial Research.7:198-204. DOI: 10.6084/m9.figshare.10298396. |
[40] | JT Kost, MP McDermott. (2002). Combining dependent P-values. Statistics & Probability Letters.60:183-190. DOI: 10.6084/m9.figshare.10298396. |
[41] | D Welter, J MacArthur, J Morales, T Burdett. et al.(2014). The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Research.42:D1001-D1006. DOI: 10.6084/m9.figshare.10298396. |
[42] | AR Wood, T Esko, J Yang, S Vedantam. et al.(2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics.46:1173-1186. DOI: 10.6084/m9.figshare.10298396. |
[43] | R Kimura, T Yamaguchi, M Takeda, O Kondo. et al.(2009). A common variation in EDAR is a genetic determinant of shovel-shaped incisors. The American Journal of Human Genetics.85:528-535. DOI: 10.6084/m9.figshare.10298396. |
[44] | G Sachse, C Church, M Stewart, H Cater. et al.(2018). FTO demethylase activity is essential for normal bone growth and bone mineralization in mice. Biochimica Et Biophysica Acta (BBA) - Molecular Basis of Disease.1864:843-850. DOI: 10.6084/m9.figshare.10298396. |
[45] | PC Sabeti, DE Reich, JM Higgins, HZ Levine. et al.(2002). Detecting recent positive selection in the human genome from haplotype structure. Nature.419:832-837. DOI: 10.6084/m9.figshare.10298396. |
[46] | TH Beaty, I Ruczinski, JC Murray, ML Marazita. et al.(2011). Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate. Genetic Epidemiology.42:469-478. DOI: 10.6084/m9.figshare.10298396. |
[47] | A Ruiz-Linares, K Adhikari, V Acuña-Alonzo, M Quinto-Sanchez. et al.(2014). Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals. PLOS Genetics.10. DOI: 10.6084/m9.figshare.10298396. |
[48] | S Birnbaum, KU Ludwig, H Reutter, S Herms. et al.(2009). Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nature Genetics.41:473-477. DOI: 10.6084/m9.figshare.10298396. |
[49] | JS Weiner. (1954). Nose shape and climate. American Journal of Physical Anthropology.12:615-618. DOI: 10.6084/m9.figshare.10298396. |
[50] | TH Beaty, JC Murray, ML Marazita, RG Munger. et al.(2010). A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nature Genetics.42:525-529. DOI: 10.6084/m9.figshare.10298396. |
[51] | DR Cordero, S Brugmann, Y Chu, R Bajpai. et al.(2011). Cranial neural crest cells on the move: their roles in craniofacial development. American Journal of Medical Genetics Part A.155:270-279. DOI: 10.6084/m9.figshare.10298396. |
[52] | JB Cole, M Manyama, E Kimwaga, J Mathayo. et al.(2016). Genomewide association study of african children identifies association of SCHIP1 and PDE8A with facial size and shape. PLOS Genetics.12. DOI: 10.6084/m9.figshare.10298396. |
[53] | H Lango Allen, K Estrada, G Lettre, SI Berndt. et al.(2010). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature.467:832-838. DOI: 10.6084/m9.figshare.10298396. |
[54] | LH Chadwick. (2012). The NIH roadmap epigenomics program data resource. Epigenomics.4:317-324. DOI: 10.6084/m9.figshare.10298396. |
[55] | P Claes, J Roosenboom, JD White, T Swigut. et al.(2018). Genome-wide mapping of global-to-local genetic effects on human facial shape. Nature Genetics.50:414-423. DOI: 10.6084/m9.figshare.10298396. |
[56] | BF Voight, S Kudaravalli, X Wen, JK Pritchard. et al.(2006). A map of recent positive selection in the human genome. PLOS Biology.4. DOI: 10.6084/m9.figshare.10298396. |
[57] | SM Weinberg, ZD Raffensperger, MJ Kesterke, CL Heike. et al.(2016). The 3D facial norms database: part 1. A Web-Based craniofacial anthropometric and image repository for the clinical and research community. The Cleft Palate-Craniofacial Journal.53:185-197. DOI: 10.6084/m9.figshare.10298396. |
[58] | G Lee, H Kim, Y Elkabetz, G Al Shamy. et al.(2007). Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells. Nature Biotechnology.25:1468-1475. DOI: 10.6084/m9.figshare.10298396. |
[59] | MK Lee, JR Shaffer, EJ Leslie, E Orlova. et al.(2017). Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2. PLOS ONE.12. DOI: 10.6084/m9.figshare.10298396. |
[60] | P Royston. (1995). Remark AS R94: a remark on algorithm AS 181: the W-test for normality. Journal of the Royal Statistical Society.44:547-551. DOI: 10.6084/m9.figshare.10298396. |
[61] | JH Ward. (1963). Hierarchical grouping to optimize an objective function. Journal of the American Statistical Association.58:236-244. DOI: 10.6084/m9.figshare.10298396. |
[62] | BL Aken, S Ayling, D Barrell, L Clarke. et al.(2016). The ensembl gene annotation system. Database.2016. DOI: 10.6084/m9.figshare.10298396. |
[63] | S Purcell, B Neale, K Todd-Brown, L Thomas. et al.(2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics.81:559-575. DOI: 10.6084/m9.figshare.10298396. |
[64] | L Qiao, Y Yang, P Fu, S Hu. et al.(2018). Genome-wide variants of eurasian facial shape differentiation and a prospective model of DNA based face prediction. Journal of Genetics and Genomics.45:419-432. DOI: 10.6084/m9.figshare.10298396. |
[65] | A Auton, LD Brooks, RM Durbin, EP Garrison. et al.(2015). A global reference for human genetic variation. Nature.526:68-74. DOI: 10.6084/m9.figshare.10298396. |
[66] | RJ Pruim, RP Welch, S Sanna, TM Teslovich. et al.(2010). LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics.26:2336-2337. DOI: 10.6084/m9.figshare.10298396. |
[67] | M Visser, RJ Palstra, M Kayser. (2015). Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter. Human Molecular Genetics.24:2649-2661. DOI: 10.6084/m9.figshare.10298396. |
[68] | M Bamshad, RC Lin, DJ Law, WC Watkins. et al.(1997). Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nature Genetics.16:311-315. DOI: 10.6084/m9.figshare.10298396. |
[69] | K Adhikari, M Fuentes-Guajardo, M Quinto-Sánchez, J Mendoza-Revilla. et al.(2016). A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation. Nature Communications.7. DOI: 10.6084/m9.figshare.10298396. |
[70] | S Cha, JE Lim, AY Park, JH Do. et al.(2018). Identification of five novel genetic loci related to facial morphology by genome-wide association studies. BMC Genomics.19. DOI: 10.6084/m9.figshare.10298396. |
[71] | S Feng, D Liu, X Zhan, MK Wing. et al.(2014). RAREMETAL: fast and powerful meta-analysis for rare variants. Bioinformatics.30:2828-2829. DOI: 10.6084/m9.figshare.10298396. |
[72] | X Zhou, M Stephens. (2012). Genome-wide efficient mixed-model analysis for association studies. Nature Genetics.44:821-824. DOI: 10.6084/m9.figshare.10298396. |
[73] | SL Prescott, R Srinivasan, MC Marchetto, I Grishina. et al.(2015). Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest. Cell.163:68-83. DOI: 10.6084/m9.figshare.10298396. |
[74] | H Zeng, AN Hoover, A Liu. (2010). PCP effector gene inturned is an important regulator of cilia formation and embryonic development in mammals. Developmental Biology.339:418-428. DOI: 10.6084/m9.figshare.10298396. |
[75] | L Paternoster, AI Zhurov, AM Toma, JP Kemp. et al.(2012). Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 associated with nasion position. The American Journal of Human Genetics.90:478-485. DOI: 10.6084/m9.figshare.10298396. |
[76] | A Zalc, R Rattenbach, F Auradé, B Cadot. et al.(2015). Pax3 and Pax7 play essential safeguard functions against environmental stress-induced birth defects. Developmental Cell.33:56-66. DOI: 10.6084/m9.figshare.10298396. |
[77] | SB Carroll. (2008). Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell.134:25-36. DOI: 10.6084/m9.figshare.10298396. |
[78] | JK Pickrell, T Berisa, JZ Liu, L Ségurel. et al.(2016). Detection and interpretation of shared genetic influences on 42 human traits. Nature Genetics.48:709-717. DOI: 10.6084/m9.figshare.10298396. |
[79] | O Canela-Xandri, K Rawlik, A Tenesa. (2018). An atlas of genetic associations in UK biobank. Nature Genetics.50:1593-1599. DOI: 10.6084/m9.figshare.10298396. |
[80] | Y Yu, X Zuo, M He, J Gao. et al.(2017). Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity. Nature Communications.8. DOI: 10.6084/m9.figshare.10298396. |
[81] | . (2012). An integrated encyclopedia of DNA elements in the human genome. Nature.489:57-74. DOI: 10.6084/m9.figshare.10298396. |
[82] | JG Buchan, RS Gray, JM Gansner, DM Alvarado. et al.(2014). Kinesin family member 6 (kif6) is necessary for spine development in zebrafish. Developmental Dynamics.243:1646-1657. DOI: 10.6084/m9.figshare.10298396. |
[83] | E Dupin, JM Coelho-Aguiar. (2013). Isolation and differentiation properties of neural crest stem cells. Cytometry Part A.83A:38-47. DOI: 10.6084/m9.figshare.10298396. |
[84] | AL Bruel, B Franco, Y Duffourd, J Thevenon. et al.(2017). Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes. Journal of Medical Genetics.54:371-380. DOI: 10.6084/m9.figshare.10298396. |
[85] | M Delous, L Baala, R Salomon, C Laclef. et al.(2007). The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nature Genetics.39:875-881. DOI: 10.6084/m9.figshare.10298396. |
[86] | J Djordjevic, AI Zhurov, S Richmond. (2016). Genetic and environmental contributions to facial morphological variation: a 3D Population-Based twin study. PLOS ONE.11. DOI: 10.6084/m9.figshare.10298396. |
[87] | ML Noback, K Harvati, F Spoor. (2011). Climate-related variation of the human nasal cavity. American Journal of Physical Anthropology.145:599-614. DOI: 10.6084/m9.figshare.10298396. |
[88] | J O'Connell, D Gurdasani, O Delaneau, N Pirastu. et al.(2014). A general approach for haplotype phasing across the full spectrum of relatedness. PLOS Genetics.10. DOI: 10.6084/m9.figshare.10298396. |
[89] | G Yu, LG Wang, Y Han, QY He. et al.(2012). clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS: A Journal of Integrative Biology.16:284-287. DOI: 10.6084/m9.figshare.10298396. |
[90] | J Yang, SH Lee, ME Goddard, PM Visscher. et al.(2011). GCTA: a tool for genome-wide complex trait analysis. The American Journal of Human Genetics.88:76-82. DOI: 10.6084/m9.figshare.10298396. |
[91] | GA Wray. (2007). The evolutionary significance of cis-regulatory mutations. Nature Reviews Genetics.8:206-216. DOI: 10.6084/m9.figshare.10298396. |
[92] | SJ Morrison, PM White, C Zock, DJ Anderson. et al.(1999). Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell.96:737-749. DOI: 10.6084/m9.figshare.10298396. |
[93] | ME Bronner, NM LeDouarin. (2012). Development and evolution of the neural crest: an overview. Developmental Biology.366:2-9. DOI: 10.6084/m9.figshare.10298396. |
[94] | BC Bjork, A Turbe-Doan, M Prysak, BJ Herron. et al.(2010). Prdm16 is required for normal palatogenesis in mice. Human Molecular Genetics.19:774-789. DOI: 10.6084/m9.figshare.10298396. |
[95] | O Delaneau, J Marchini, J-F Zagury. (2012). A linear complexity phasing method for thousands of genomes. Nature Methods.9:179-181. DOI: 10.6084/m9.figshare.10298396. |
[96] | A Boyd, J Golding, J Macleod, DA Lawlor. et al.(2013). Cohort profile: the 'children of the 90s'--the index offspring of the Avon Longitudinal Study of Parents and Children. International Journal of Epidemiology.42:111-127. DOI: 10.6084/m9.figshare.10298396. |
[97] | MA de Jong, P Hysi, T Spector, W Niessen. et al.(2018). Ensemble landmarking of 3D facial surface scans. Scientific Reports.8. DOI: 10.6084/m9.figshare.10298396. |

浏览 | 141次 |
下载全文 | 73次 |
评分次数 | 0次 |
用户评分
![]() ![]() ![]() ![]() ![]() |
0.0分 |
分享 | 0次 |

- 1.ARL3 activation requires the co-GEF BART and effector-mediated turnover
- 2.Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci
- 3.Modeling transfer of vaginal microbiota from mother to infant in early life
- 4.The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression
- 5.Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection
- 6.Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells
- 7.Rapid adaptation to malaria facilitated by admixture in the human population of Cabo Verde
- 8.Checkpoint inhibition of origin firing prevents inappropriate replication outside of S-phase
- 9.Oxytocin modulates human chemosensory decoding of sex in a dose-dependent manner
- 10.A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies
- 11.Human complex exploration strategies are enriched by noradrenaline-modulated heuristics
- 12.A multidisciplinary approach to the study of insular environments: the 1st Summer School on Geomorphology, Ecology, and Marine Biology in the Tremiti Islands (Southern Adriatic Sea, Puglia, Italy)