Revealing rate-limiting steps in complex disease biology: The crucial importance of studying rare, extreme-phenotype families

BioEssays

Volumn 38, Issue 6, 2016, Pages 578-586

  Chakravarti, Aravinda ^a   Turner, Tychele N ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Complex inheritance; Extreme phenotype; Gene regulatory network; Genetic disease

Indexed keywords

TRANSCRIPTION FACTOR;

ARTICLE; BIOLOGICAL TRAIT; FEEDBACK SYSTEM; GENE REGULATORY NETWORK; GENE SEQUENCE; GENETIC REGULATION; GENETIC TRANSCRIPTION; GENOMICS; HUMAN; INHERITANCE; PHENOTYPE; REGULATORY SEQUENCE; FEMALE; GENETIC DISORDER; MALE; MUTATION; PEDIGREE;

FEMALE; GENE REGULATORY NETWORKS; GENETIC DISEASES, INBORN; GENOMICS; HUMANS; MALE; MUTATION; PEDIGREE; PHENOTYPE;

EID: 84963900727     PISSN: 02659247     EISSN: 15211878     Source Type: Journal    
DOI: 10.1002/bies.201500203     Document Type: Article

References (36)

1. Committee on Mapping & Sequencing the Human Genome, National Research Council. 1988. Mapping and Sequencing the Human Genome. Washington, D.C.: National Academies Press.
2. Chakravarti A, Clark AG, Mootha VK. 2013. Distilling pathophysiology from complex disease genetics. Cell 155: 21-6.
3. Childs B. 1999. Genetic Medicine: A Logic of Disease. Baltimore: Johns Hopkins University Press.
4. Committee on a Framework for Development a New Taxonomy of Disease, National Research Council. 2011. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington, D.C.: National Academies Press.
5. Mayr E, Provine WB. 1980. The Evolutionary Synthesis: Perspectives on the Unification of Biology. Cambridge, MA: Harvard University Press.
6. Antonarakis SE, Chakravarti A, Cohen JC, Hardy J. 2010. Mendelian disorders and multifactorial traits: the big divide or one for all? Nat Rev Genet 11: 380-4.
7. Fisher RA. 1918. The correlation between relatives on the supposition of Mendelian inheritance. Philos T Roy Soc Edinburgh 52: 399-433.
8. International Human Genome Sequencing Consortium. 2001. Initial sequencing and analysis of the human genome. Nature 409: 860-921.
9. Human Genome Sequencing Consortium I. 2004. Finishing the euchromatic sequence of the human genome. Nature 431: 931-45.
10. Chong JX, Buckingham KJ, Jhangiani SN, Boehm C, et al. 2015. The genetic basis of mendelian phenotypes: discoveries, challenges, and opportunities. Am J Hum Genet 97: 199-215.
11. Welter D, MacArthur J, Morales J, Burdett T, et al. 2014. The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42: D1001-6.
12. Turner TN, Douville C, Kim D, Stenson PD, et al. 2015. Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns. Hum Mol Genet 24: 5995-6002.
13. Boone C, Bussey H, Andrews BJ. 2007. Exploring genetic interactions and networks with yeast. Nat Rev Genet 8: 437-49.
14. Chakravarti A. 2011. Genomic contributions to Mendelian disease. Genome Res 21: 643-4.
15. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, et al. 2009. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106: 9362-7.
16. Wood AR, Esko T, Yang J, Vedantam S, et al. 2014. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 46: 1173-86.
17. Willer CJ, Schmidt EM, Sengupta S, Peloso GM, et al. 2013. Discovery and refinement of loci associated with lipid levels. Nat Genet 45: 1274-83.
18. Locke AE, Kahali B, Berndt SI, Justice AE, et al. 2015. Genetic studies of body mass index yield new insights for obesity biology. Nature 518: 197-206.
19. Mohlke KL, Boehnke M. 2015. Recent advances in understanding the genetic architecture of type 2 diabetes. Hum Mol Genet 24: R85-92.
20. Emison ES, McCallion AS, Kashuk CS, Bush RT, et al. 2005. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 434: 857-63.
21. Emison ES, Garcia-Barcelo M, Grice EA, Lantieri F, et al. 2010. Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am J Hum Genet 87: 60-74.
22. Coste B, Houge G, Murray MF, Stitziel N, et al. 2013. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proc Natl Acad Sci USA 110: 4667-72.
23. Dixon JR, Selvaraj S, Yue F, Kim A, et al. 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485: 376-80.
24. Phillips-Cremins JE. 2014. Unraveling architecture of the pluripotent genome. Curr Opin Cell Biol 28: 96-104.
25. Maurano MT, Haugen E, Sandstrom R, Vierstra J, et al. 2015. Large-scale identification of sequence variants influencing human transcription factor occupancy in vivo. Nat Genet 47: 1393-401.
26. Finucane H. 2014. Nature Genomics of Complex Disease Conference.
27. Alon U. 2007. An Introduction to Systems Biology: Design Principles of Biological Circuits. Boca Raton, FL: Chapman & Hall/CRC.
28. Davidson EH. 2006. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution. Academic Press.
29. Iossifov I, O'Roak BJ, Sanders SJ, Ronemus M, et al. 2014. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515: 216-21.
30. Nurse P. Emerging themes in biology: Hints for the future. Cell 157: 272-3.
31. Falconer DS. 1965. The inheritance of liability to certain diseases, estimated from incidence among relatives. Ann Hum Genet 29: 51-76.
32. Carter CO. 1969. Genetics of common disorders. Br Med Bull 25: 52-7.
33. Hall JM, Lee MK, Newman B, Morrow JE, et al. 1990. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250: 1684-9.
34. Turner TN, Sharma K, Oh EC, Liu YP, et al. 2015. Loss of delta-catenin function in severe autism. Nature 520: 51-6.
35. Israely I, Costa RM, Xie CW, Silva AJ, et al. 2004. Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction. Curr Biol 14: 1657-63.
36. Matter C, Pribadi M, Liu X, Trachtenberg JT. 2009. Delta-catenin is required for the maintenance of neural structure and function in mature cortex in vivo. Neuron 64: 320-7.