Junk DNA: A Journey Through the Dark Matter of the Genome (46 page)

  
2
. For a review of this, see Moltó E, Fernández A, Montoliu L. Boundaries in vertebrate genomes: different solutions to adequately insulate gene expression domains.
Brief Funct Genomic Proteomic
. 2009 Jul;8(4):283–96

  
3
. Ishihara K, Oshimura M, Nakao M. CTCF-dependent chromatin insulator is linked to epigenetic remodeling.
Mol Cell
. 2006 Sep 1;23(5):733–42

  
4
. Lutz M, Burke LJ, Barreto G, Goeman F, Greb H, Arnold R, Schultheiss H, Brehm A, Kouzarides T, Lobanenkov V, Renkawitz R. Transcriptional repression by the insulator protein CTCF involves histone deacetylases.
Nucleic Acids Res
. 2000 Apr 15;28(8):1707–13

  
5
. Lunyak VV, Prefontaine GG, Núñez E, Cramer T, Ju BG, Ohgi KA, Hutt K, Roy R, García-Díaz A, Zhu X, Yung Y, Montoliu L, Glass CK, Rosenfeld MG. Developmentally regulated activation of a SINE B2 repeat as a domain boundary in organogenesis.
Science
. 2007 Jul 13;317(5835):248–51

  
6
. Reviewed in Kirkland JG, Raab JR, Kamakaka RT. TFIIIC bound DNA elements in nuclear organization and insulation.
Biochim Biophys Acta
. 2013 Mar–Apr;1829(3–4):418–24

  
7
. This is known as Turner’s syndrome and more information can be found at
http://www.nhs.uk/Conditions/Turners-syndrome/Pages/Introduction.aspx

  
8
. For more information see
http://ghr.nlm.nih.gov/condition/triple-x-syndrome

  
9
. This condition is known as Klinefelter’s syndrome and more information can be found at
http://ghr.nlm.nih.gov/condition/klinefelter-syndrome

10
.
Star Trek: First Contact
(1996). By far the best of all the Star Trek movies, at least until the JJ Abrams franchise reboot.

11
. See
https://ghr.nlm.nih.gov/gene/SHOX

12
. Hemani G, Yang J, Vinkhuyzen A, Powell JE, Willemsen G, Hottenga JJ, Abdellaoui A, Mangino M, Valdes AM, Medland SE, Madden PA, Heath AC, Henders AK, Nyholt DR, de Geus EJ, Magnusson PK, Ingelsson E, Montgomery GW, Spector TD, Boomsma DI, Pedersen NL, Martin NG, Visscher PM. Inference of the genetic architecture underlying BMI and height with the use of 20,240 sibling pairs.
Am J Hum Genet
. 2013 Nov 7;93(5):865–75

Chapter 14

  
1
. A wealth of information about ENCODE, including interviews with some of the leading scientists, can be accessed at
http://www.nature.com/encode/

  
2
.
http://www.theguardian.com/science/2012/sep/05/genes-genome-junk-dna-encode

  
3
.
http://edition.cnn.com/2012/09/05/health/encode-human-genome/index.html?hpt=hp_bn12

  
4
.
http://www.telegraph.co.uk/science/science-news/9524165/Worldwide-army-of-scientists-cracks-the-junk-DNA-code.html

  
5
. ENCODE Project Consortium, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M. An integrated encyclopedia of DNA elements in the human genome.
Nature
. 2012 Sep 6;489(7414):57–74

  
6
. Mattick JS. A new paradigm for developmental biology.
J Exp Biol
. 2007 May;210(Pt 9):1526–47

  
7
. Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters.
Nature
. 2012 Sep 6;489(7414):109–13

  
8
. Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, Garg K, John S, Sandstrom R, Bates D, Boatman L, Canfield TK, Diegel M, Dunn D, Ebersol AK, Frum T, Giste E, Johnson AK, Johnson EM, Kutyavin T, Lajoie B, Lee BK, Lee K, London D, Lotakis D, Neph S, Neri F, Nguyen ED, Qu H, Reynolds AP, Roach V, Safi A, Sanchez ME, Sanyal A, Shafer A, Simon JM, Song L, Vong S, Weaver M, Yan Y, Zhang Z, Zhang Z, Lenhard B, Tewari M, Dorschner MO, Hansen RS, Navas PA, Stamatoyannopoulos G, Iyer VR, Lieb JD, Sunyaev SR, Akey JM, Sabo PJ, Kaul R, Furey TS, Dekker J, Crawford GE, Stamatoyannopoulos JA. The accessible chromatin landscape of the human genome.
Nature
. 2012 Sep 6;489(7414):75–82

  
9
. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR. Landscape of transcription in human cells.
Nature
. 2012 Sep 6;489(7414):101–8

10
. I originally used this description in a Huffington Post blog about the ENCODE project. I’ve decided I like it so much I will use it again here! For the original blog, see
http://www.huffingtonpost.com/nessa-carey/the-value-of-encode_b_1909153.html

11
. A good example can be found at
http://blog.art21.org/2009/03/06/on-representations-of-the-artist-at-work-part-2/#.UyDZjZZFDIU

12
. Ward LD, Kellis M. Evidence of abundant purifying selection in humans for recently acquired regulatory functions.
Science
. 2012 Sep 28;337(6102):1675–8.

13
. Ecker JR, Bickmore WA, Barroso I, Pritchard JK, Gilad Y, Segal E. Genomics: ENCODE explained.
Nature
. 2012 Sep 6;489(7414)

14
. For a fascinating example of epigenetic transgenerational inheritance see this paper, in which a fear response was passed on from parent to pups: Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations.
Nat Neurosci
. 2014 Jan;17(1):89–96

15
. Graur D, Zheng Y, Price N, Azevedo RB, Zufall RA, Elhaik E. On the immortality of television sets: ‘function’ in the human genome according to the evolution-free gospel of ENCODE.
Genome Biol Evol
. 2013;5(3):578–90

Chapter 15

  
1
.
http://womenshistory.about.com/od/mythsofwomenshistory/a/Did-Anne-Boleyn-Really-Have-Six-Fingers-On-One-Hand.htm

  
2
. Lettice LA, Heaney SJ, Purdie LA, Li L, de Beer P, Oostra BA, Goode D, Elgar G, Hill RE, de Graaff E. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly.
Hum Mol Genet
. 2003 Jul 15;12(14):1725–35

  
3
.
www.hemingwayhome.com/cats/

  
4
. Lettice LA, Hill AE, Devenney PS, Hill RE. Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly.
Hum Mol Genet
. 2008 Apr 1;17(7):978–85

  
5
. For a fuller description, see
http://www.genome.gov/12512735

  
6
. Jeong Y, Leskow FC, El-Jaick K, Roessler E, Muenke M, Yocum A, Dubourg C, Li X, Geng X, Oliver G, Epstein DJ. Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein.
Nat Genet
. 2008 Nov;40(11):1348–53

  
7
. For more information see
http://rarediseases.info.nih.gov/gard/10874/pancreatic-agenesis/resources/1

  
8
. Lango Allen H, Flanagan SE, Shaw-Smith C, De Franco E, Akerman I, Caswell R; International Pancreatic Agenesis Consortium, Ferrer J, Hattersley AT, Ellard S. GATA6 haploinsufficiency causes pancreatic agenesis in humans.
Nat Genet
. 2011 Dec 11;44(1):20–2

  
9
. Sellick GS, Barker KT, Stolte-Dijkstra I, Fleischmann C, Coleman RJ, Garrett C, Gloyn AL, Edghill EL, Hattersley AT, Wellauer PK, Goodwin G, Houlston RS. Mutations in PTF1A cause pancreatic and cerebellar agenesis.
Nat Genet
. 2004 Dec;36(12):1301–5

10
. Weedon MN, Cebola I, Patch AM, Flanagan SE, De Franco E, Caswell R, Rodríguez-Seguí SA, Shaw-Smith C, Cho CH, Lango Allen H, Houghton JA, Roth CL, Chen R, Hussain K, Marsh P, Vallier L, Murray A; International Pancreatic Agenesis Consortium, Ellard S, Ferrer J, Hattersley AT. Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.
Nat Genet
. 2014 Jan;46(1):61–4

11
. For a review of this, see Sturm RA. Molecular genetics of human pigmentation diversity.
Hum Mol Genet
. 2009 Apr 15;18(R1):R9–17

12
. Durham-Pierre D, Gardner JM, Nakatsu Y, King RA, Francke U, Ching A, Aquaron R, del Marmol V, Brilliant MH. African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism.
Nat Genet
. 1994 Jun;7(2):176–9

13
. Visser M, Kayser M, Palstra RJ. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter.
Genome Res
. 2012 Mar;22(3):446–55

14
. For an up-to-date catalogue, see
www.genome.gov/gwastudies/

15
. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
Proc Natl Acad Sci U S A
. 2009 Jun 9;106(23):9362–7

16
. Gorkin DU, Ren B. Genetics: Closing the distance on obesity culprits.
Nature
. 2014 Mar 20;507(7492):309–10

17
. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.
Science
. 2007 May 11;316(5826):889–94

18
. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.
PLoS Genet
. 2007 Jul;3(7):e115