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The road ahead in genetics and genomics

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McGuire, Amy L., Gabriel, Stacey, Tishkoff, Sarah A., Wonkam, Ambroise, Chakravarti, Aravinda, Furlong, Eileen E. M., Treutlein, Barbara, Meissner, Alexander +4 more·2020·Nature Reviews Genetics
DOI 10.1038/s41576-020-0272-6PMC PMC7444682
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Abstract

In celebration of the 20th anniversary of Nature Reviews Genetics, we asked 12 leading researchers to reflect on the key challenges and opportunities faced by the field of genetics and genomics. Keeping their particular research area in mind, they take stock of the current state of play and emphasize the work that remains to be done over the next few years so that, ultimately, the benefits of genetic and genomic research can be felt by everyone.

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  1. [6]Popejoy AB The clinical imperative for inclusivity: race, ethnicity, and ancestry (REA) in genomics Hum. Mutat. 2018 39 1713 1720 30311373 PMC6188707
  2. [8]Armstrong K Micco E Carney A Stopfer J Putt M Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer JAMA 2005 293 1729 1736 15827311
  3. [9]Bonham VL Callier SL Royal CD Will precision medicine move us beyond race? N. Engl. J. Med. 2016 374 2003 2005 27223144 PMC5621043
  4. [10]Karczewski KJ The mutational constraint spectrum quantified from variation in 141,456 humans Nature 2020 581 434 443 32461654 PMC7334197
  5. [12]The SIGMA Type 2 Diabetes Consortium Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico Nature 2014 506 97 101 24390345 PMC4127086
  6. [14]Wall JD The GenomeAsia 100K Project enables genetic discoveries across Asia Nature 2019 576 106 111 31802016 PMC7054211
  7. [15]Kowalski MH Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations PLoS Genet. 2019 15 e1008500 31869403 PMC6953885
  8. [16]Bycroft C The UK Biobank resource with deep phenotyping and genomic data Nature 2018 562 203 209 30305743 PMC6786975
  9. [17]Gaziano JM Million veteran program: a mega-biobank to study genetic influences on health and disease J. Clin. Epidemiol. 2016 70 214 223 26441289
  10. [18]Nagai A Overview of the BioBank Japan Project: study design and profile J. Epidemiol. 2017 27 S2 S8 28189464 PMC5350590
  11. [19]Denny JC Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data Nat. Biotechnol. 2013 31 1102 1110 24270849 PMC3969265
  12. [20]Sirugo G Williams SM Tishkoff SA The missing diversity in human genetic studies Cell 2019 177 1080 31051100
  13. [22]McQuillan MA Zhang C Tishkoff SA Platt A The importance of including ethnically diverse populations in studies of quantitative trait evolution Curr. Opin. Genet. Dev. 2020 62 30 35 32604012 PMC7942184
  14. [23]Sohail M Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies eLife 2019 8 e39702 30895926 PMC6428571
  15. [24]Crawford NG Loci associated with skin pigmentation identified in African populations Science 2017 358 eaan8433 29025994 PMC5759959
  16. [25]Gasperini M Tome JM Shendure J Towards a comprehensive catalogue of validated and target-linked human enhancers Nat. Rev. Genet. 2020 21 292 310 31988385 PMC7845138
  17. [26]Racimo F Sankararaman S Nielsen R Huerta-Sánchez E Evidence for archaic adaptive introgression in humans Nat. Rev. Genet. 2015 16 359 371 25963373 PMC4478293
  18. [27]Skoglund P Mathieson I Ancient genomics of modern humans: the first decade Annu. Rev. Genomics Hum. Genet. 2018 19 381 404 29709204
  19. [28]Vicente M Schlebusch CM African population history: an ancient DNA perspective Curr. Opin. Genet. Dev. 2020 62 8 15 32563853
  20. [29]Sherman RM Assembly of a pan-genome from deep sequencing of 910 humans of African descent Nat. Genet. 2019 51 30 35 30455414 PMC6309586
  21. [30]Durvasula A Recovering signals of ghost archaic introgression in African populations Sci. Adv. 2020 12 eaax5097 PMC7015685 32095519
  22. [32]Adeyemo AA ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response Nat. Commun. 2019 10 3195 31324766 PMC6642147
  23. [33]Cohen J Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 Nat. Genet. 2005 37 161 165 15654334
  24. [34]Gurdasani D Uganda genome resource enables insights into population history and genomic discovery in Africa Cell 2019 179 984 002.e36 31675503 PMC7202134
  25. [35]Gurdasani D Genomics of disease risk in globally diverse populations Nat. Rev. Genet. 2019 20 520 535 31235872
  26. [36]Gulsuner S Genetics of schizophrenia in the South African Xhosa Science 2020 367 569 573 32001654 PMC9558321
  27. [38]Wu Y Highly efficient therapeutic gene editing of human haematopoietic stem cells Nat. Med. 2019 25 776 783 30911135 PMC6512986
  28. [39]Geard A Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon Br. J. Haematol. 2017 178 629 639 28466968 PMC5660286
  29. [40]Lebeko K Targeted genomic enrichment and massively parallel sequencing identifies novel nonsyndromic hearing impairment pathogenic variants in Cameroonian families Clin. Genet. 2016 90 288 290 27246798 PMC5324826
  30. [41]Genovese G Association of trypanolytic ApoL1 variants with kidney disease in African Americans Science 2010 329 841 845 20647424 PMC2980843
  31. [42]Sierra B OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans PLoS Pathog. 2017 13 e1006220 28241052 PMC5344536
  32. [43]Wonkam A de Vries J Returning incidental findings in African genomics research Nat. Genet. 2020 52 17 20 31768070 PMC7255819
  33. [44]Provine, W. B. The Origins of Theoretical Population Genetics (University of Chicago Press, 1971)
  34. [45]Fisher RA The correlation between relatives on the supposition of Mendelian inheritance Trans. R. Soc. Edinb. 1918 52 399 433
  35. [46]Altenburg E Muller HJ The genetic basis of truncate wing – an inconstant and modifiable character in Drosophila Genetics 1920 5 1 59 17245940 PMC1200474
  36. [47]Morton NE Analysis of family resemblance. I. Introduction Am. J. Hum. Genet. 1974 26 318 330 4827365 PMC1762618
  37. [48]Visscher PM 10 Years of GWAS discovery: biology, function and translation Am. J. Hum. Genet. 2017 101 5 22 28686856 PMC5501872
  38. [49]Boyle EA Li YI Pritchard JK An expanded view of complex traits: from polygenic to omnigenic Cell 2017 169 1177 1186 28622505 PMC5536862
  39. [50]Emison ES A common, sex-dependent mutation in a putative RET enhancer underlies Hirschsprung disease susceptibility Nature 2005 434 857 863 15829955
  40. [52]Davidson E Emerging properties of animal gene regulatory networks Nature 2010 468 911 920 21164479 PMC3967874
  41. [53]Chatterjee S Enhancer variants synergistically drive dysregulation of the RET gene regulatory network in Hirschsprung disease Cell 2016 167 355 368 27693352 PMC5113733
  42. [54]Segal E Raveh-Sadka T Schroeder M Unnerstall U Gaul U Predicting expression patterns from regulatory sequence in Drosophila segmentation Nature 2008 451 535 540 18172436
  43. [55]Chakravarti A Turner TN Revealing rate-limiting steps in complex disease biology: The crucial importance of studying rare, extreme-phenotype families Bioessays 2016 38 578 586 27062178
  44. [57]Rothman J Jarriault S Developmental plasticity and cellular reprogramming in caenorhabditis elegans Genetics 2019 213 723 757 31685551 PMC6827377
  45. [58]Porrello ER Transient regenerative potential of the neonatal mouse heart Science 2011 331 1078 1080 21350179 PMC3099478
  46. [59]Mir M Bickmore W Furlong EEM Narlikar G Chromatin topology, condensates and gene regulation: shifting paradigms or just a phase? Development 2019 146 dev182766 31554625 PMC6803379
  47. [61]Despang A Functional dissection of the Sox9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture Nat. Genet. 2019 51 1263 1271 31358994
  48. [62]Hnisz D Shrinivas K Young RA Chakraborty AK Sharp PA A phase separation model for transcriptional control Cell 2017 169 13 23 28340338 PMC5432200
  49. [63]Shrinivas K Enhancer features that drive formation of transcriptional condensates Mol. Cell 2019 75 549 561 e547 31398323 PMC6690378
  50. [64]Narlikar GJ Phase-separation in chromatin organization J. Biosci. 2020 45 5 31965983 PMC9107952
  51. [65]Cao J The single-cell transcriptional landscape of mammalian organogenesis Nature 2019 566 496 502 30787437 PMC6434952
  52. [67]Cusanovich DA The cis-regulatory dynamics of embryonic development at single-cell resolution Nature 2018 555 538 542 29539636 PMC5866720
  53. [68]Tang F mRNA-Seq whole-transcriptome analysis of a single cell Nat. Methods 2009 6 377 382 19349980
  54. [69]Camp JG Platt R Treutlein B Mapping human cell phenotypes to genotypes with single-cell genomics Science 2019 365 1401 1405 31604266
  55. [72]Achim K High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin Nat. Biotechnol. 2015 33 503 509 25867922
  56. [73]Cao J Comprehensive single-cell transcriptional profiling of a multicellular organism Science 2017 357 661 667 28818938 PMC5894354
  57. [74]Cleary B Cong L Cheung A Lander ES Regev A Efficient generation of transcriptomic profiles by random composite measurements Cell 2017 171 1424 1436 e1418 29153835 PMC5726792
  58. [77]Stuart T Satija R Integrative single-cell analysis Nat. Rev. Genet. 2019 20 257 272 30696980
  59. [78]Zhu C Preissl S Ren B Single-cell multimodal omics: the power of many Nat. Methods 2020 17 11 14 31907462
  60. [79]Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. (2020). 32572269
  61. [80]Loeffler D Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells Nature 2019 573 426 429 31485073
  62. [81]Schmidt F Cherepkova MY Platt RJ Transcriptional recording by CRISPR spacer acquisition from RNA Nature 2018 562 380 385 30283135
  63. [82]Holliday R Pugh JE DNA modification mechanisms and gene activity during development Science 1975 187 226 232 1111098
  64. [83]Strahl BD Allis CD The language of covalent histone modifications Nature 2000 403 41 45 10638745
  65. [84]Jambhekar A Dhall A Shi Y Roles and regulation of histone methylation in animal development Nat. Rev. Mol. Cell Biol. 2019 20 625 641 31267065 PMC6774358
  66. [86]Jinek M A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity Science 2012 337 816 821 22745249 PMC6286148
  67. [87]Nabet B The dTAG system for immediate and target-specific protein degradation Nat. Chem. Biol. 2018 14 431 441 29581585 PMC6295913
  68. [90]Banani SF Lee HO Hyman AA Rosen MK Biomolecular condensates: organizers of cellular biochemistry Nat. Rev. Mol. Cell Biol. 2017 18 285 298 28225081 PMC7434221
  69. [91]Lupianez DG Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions Cell 2015 161 1012 1025 25959774 PMC4791538
  70. [92]Basu S Unblending of transcriptional condensates in human repeat expansion disease Cell 2020 181 1062 1079 e1030 32386547 PMC7261253
  71. [93]Grosswendt S Epigenetic regulator function through mouse gastrulation Nature 2020 584 102 108 32728215 PMC7415732
  72. [95]Heard E Ten years of genetics and genomics: what have we achieved and where are we heading? Nat. Rev. Genet. 2010 11 723 733 20820184 PMC3004366
  73. [96]Quinn JJ Chang HY Unique features of long non-coding RNA biogenesis and function Nat. Rev. Genet. 2016 17 47 62 26666209
  74. [97]Kopp F Mendell JT Functional classification and experimental dissection of long noncoding RNAs Cell 2018 172 393 407 29373828 PMC5978744
  75. [98]Liu SJ CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells Science 2017 355 eaah7111 PMC5394926 27980086
  76. [100]Quinn JJ Rapid evolutionary turnover underlies conserved lncRNA-genome interactions Genes. Dev. 2016 30 191 207 26773003 PMC4719309
  77. [101]Kirk JM Functional classification of long non-coding RNAs by k-mer content Nat. Genet. 2018 50 1474 1482 30224646 PMC6262761
  78. [102]Carter AC Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation eLife 2020 9 e54508 32379046 PMC7282817
  79. [103]Lubelsky Y Ulitsky I Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells Nature 2018 555 107 111 29466324 PMC6047738
  80. [104]Shukla CJ High-throughput identification of RNA nuclear enrichment sequences EMBO J. 2018 37 e98452 29335281 PMC5852646
  81. [105]Czerminski JT Lawrence JB Silencing Trisomy 21 with XIST in neural stem cells promotes neuronal differentiation Dev. Cell 2020 52 294 308 e3 31978324 PMC7055611
  82. [106]Martínez-Jiménez F A compendium of mutational cancer driver genes Nat. Rev. Cancer 2020 10.1038/s41568-020-0290-x 32778778 · DOI
  83. [108]Alexandrov LB The repertoire of mutational signatures in human cancer Nature 2020 578 94 101 32025018 PMC7054213
  84. [109]Gonzalez-Perez A Radhakrishnan S Lopez-Bigas N Local determinants of the mutational landscape of the human genome Cell 2019 177 101 114 30901533
  85. [110]Martincorena I High burden and pervasive positive selection of somatic mutations in normal human skin Science 2015 348 880 886 25999502 PMC4471149
  86. [111]Martincorena I Somatic mutant clones colonize the human esophagus with age Science 2018 362 911 917 30337457 PMC6298579
  87. [113]Genovese G Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence N. Engl. J. Med. 2014 371 2477 2487 25426838 PMC4290021
  88. [115]Sabarinathan, R. et al. The whole-genome panorama of cancer drivers. Preprint at bioRxiv10.1101/190330 (2017).
  89. [116]Pich O The mutational footprints of cancer therapies Nat. Genet. 2019 51 1732 1740 31740835 PMC6887544
  90. [119]ENCODE Project Consortium An integrated encyclopedia of DNA elements in the human genome Nature 2012 489 57 74 22955616 PMC3439153
  91. [120]Damodaran S Cancer Driver Log (CanDL): catalog of potentially actionable cancer mutations J. Mol. Diagn. 2015 17 554 559 26320871 PMC4597274
  92. [122]Shilo S Rossman H Segal E Axes of a revolution: challenges and promises of big data in healthcare Nat. Med. 2020 26 29 38 31932803
  93. [123]Kotler E A systematic p53 mutation library links differential functional impact to cancer mutation pattern and evolutionary conservation Mol. Cell 2018 71 873 30193102 PMC6127029
  94. [125]Maini Rekdal V Bess EN Bisanz JE Turnbaugh PJ Balskus EP Discovery and inhibition of an interspecies gut bacterial pathway for levodopa metabolism Science 2019 364 eaau6323 31196984 PMC7745125
  95. [126]Hernán MA Robins JM Using big data to emulate a target trial when a randomized trial is not available Am. J. Epidemiol. 2016 183 758 764 26994063 PMC4832051
  96. [128]Kim J-S Genome editing comes of age Nat. Protoc. 2016 11 1573 1578 27490630
  97. [129]Kim D Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells Nat. Methods 2015 12 237 243 25664545
  98. [131]Wienert B Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq Science 2019 364 286 289 31000663 PMC6589096
  99. [132]Kosicki M Tomberg K Bradley A Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements Nat. Biotechnol. 2018 36 765 771 30010673 PMC6390938
  100. [135]Anzalone AV Search-and-replace genome editing without double-strand breaks or donor DNA Nature 2019 576 149 157 31634902 PMC6907074

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Authors
McGuire, A. L., Gabriel, S., Tishkoff, S. A., Wonkam, A., Chakravarti, A., Furlong, E. E. M., Treutlein, B., Meissner, A., Chang, H. Y., López-Bigas, N., Segal, E., & Kim, J.-S.
Affiliations
  • Baylor College of Medicine (US)
  • Broad Institute (US)
  • University of Pennsylvania (US)
  • University of Cape Town (ZA)
  • New York University (US)
  • European Molecular Biology Laboratory (DE)
  • ETH Zurich (CH)
  • Howard Hughes Medical Institute (US)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • Weizmann Institute of Science (IL)
  • Institute for Basic Science (KR)
Corresponding author
  • McGuire, Amy L.
  • Gabriel, Stacey
  • Tishkoff, Sarah A.
  • Wonkam, Ambroise
  • Chakravarti, Aravinda
  • Furlong, Eileen E. M.
  • Treutlein, Barbara
  • Meissner, Alexander
  • Chang, Howard Y.
  • López-Bigas, Núria
  • Segal, Eran
  • Kim, Jin-Soo
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2020-08-24
Volume
21
Issue
10
Pages
581-596
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/s41576-020-0272-6
PMC
PMC7444682
OpenAlex
W3081391674
Cited by
188
References
30
Citations by year
2026: 5 · 2025: 26 · 2024: 37 · 2023: 45 · 2022: 39 · 2021: 32 · 2020: 4
FWCI
4.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Wellcome Trust (H3A/18/001)
  • National Heart, Lung, and Blood Institute (U24HL135600)
  • National Human Genome Research Institute (RM1HG007735, U01HG007459, P50HG007735, U54HG009790, U01HG009716)
  • National Cancer Institute (R35CA209919)
  • National Institute of General Medical Sciences (R35GM134957)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR076241)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD028088)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Science, Research, and Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genetics, Bioinformatics, and Biomedical Research
Keywords
genetics, genomics, future challenges, personalized medicine, genomic research ethics, genomic data sharing, human genetic variation, human evolution, precision medicine, clinical genomics, research capacity building
MeSH terms
Disease, Genetics, Humans, Genome, Human, Genomics, Genome-Wide Association Study

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