Junk DNA: A Journey Through the Dark Matter of the Genome (47 page)

19
. Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Brüning JC, Nolan PM, Ashcroft FM, Cox RD. Overexpression of Fto leads to increased food intake and results in obesity.
Nat Genet
. 2010 Dec;42(12):1086–92

20
. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U. Inactivation of the Fto gene protects from obesity.
Nature
. 2009 Apr 16;458(7240):894–8

21
. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA. Obesity-associated variants within FTO form long-range functional connections with IRX3.
Nature
. 2014 Mar 20;507(7492):371–5

22
. For a recent review of this field see Trent RJ, Cheong PL, Chua EW, Kennedy MA. Progressing the utilisation of pharmacogenetics and pharmacogenomics into clinical care.
Pathology
. 2013 Jun;45(4):357–70

23
.
http://www.nhs.uk/Conditions/Herceptin/Pages/Introduction.aspx

24
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http://www.nature.com/scitable/topicpage/gleevec-the-breakthrough-in-cancer-treatment-565

25
.
http://www.cancer.gov/cancertopics/druginfo/fda-crizotinib

Chapter 16

  
1
. Examples of such cases can be found at
http://medicalmisdiagnosisresearch.wordpress.com/category/osteogenesis-imperfecta-misdiagnosed-as-child-abuse/

  
2
. For a good description of the symptoms and genetics, see
http://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta

  
3
. Cho TJ, Lee KE, Lee SK, Song SJ, Kim KJ, Jeon D, Lee G, Kim HN, Lee HR, Eom HH, Lee ZH, Kim OH, Park WY, Park SS, Ikegawa S, Yoo WJ, Choi IH, Kim JW. A single recurrent mutation in the 5′-UTR of IFITM5 causes osteogenesis imperfecta type V.
Am J Hum Genet
. 2012 Aug 10;91(2):343–8

  
4
. Semler O, Garbes L, Keupp K, Swan D, Zimmermann K, Becker J, Iden S, Wirth B, Eysel P, Koerber F, Schoenau E, Bohlander SK, Wollnik B, Netzer C. A mutation in the 5′-UTR of IFITM5 creates an in-frame start codon and causes autosomal-dominant osteogenesis imperfecta type V with hyperplastic callus.
Am J Hum Genet
. 2012 Aug 10;91(2):349–57

  
5
. Moffatt P, Gaumond MH, Salois P, Sellin K, Bessette MC, Godin E, de Oliveira PT, Atkins GJ, Nanci A, Thomas G. Bril: a novel bone-specific modulator of mineralization.
J Bone Miner Res
. 2008 Sep;23(9):1497–508

  
6
. Liu L, Dilworth D, Gao L, Monzon J, Summers A, Lassam N, Hogg D. Mutation of the CDKN2A 5′ UTR creates an aberrant initiation codon and predisposes to melanoma.
Nat Genet
. 1999 Jan;21(1):128–32

  
7
. Tietze JK, Pfob M, Eggert M, von Preußen A, Mehraein Y, Ruzicka T, Herzinger T. A non-coding mutation in the 5′ untranslated region of patched homologue 1 predisposes to basal cell carcinoma.
Exp Dermatol
. 2013 Dec;22(12):834–5

  
8
. For a full description see
http://omim.org/entry/309550

  
9
. Ashley CT Jr, Wilkinson KD, Reines D, Warren ST. FMR1 protein: conserved RNP family domains and selective RNA binding.
Science
. 1993 Oct 22;262(5133):563–6

10
. Qin M, Kang J, Burlin TV, Jiang C, Smith CB. Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse.
J Neurosci
. 2005 May 18;25(20):5087–95

11
. Azevedo FA, Carvalho LR, Grinberg LT, Farfel JM, Ferretti RE, Leite RE, Jacob Filho W, Lent R, Herculano-Houzel S. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain.
J Comp Neurol
. 2009 Apr 10;513(5):532–41

12
. Drachman DA. Do we have brain to spare?
Neurology
. 2005 Jun 28;64(12):2004–5

13
. Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, Stone EF, Chen C, Fak JJ, Chi SW, Licatalosi DD, Richter JD, Darnell RB. FMRP stalls ribosomal translocation on messenger RNAs linked to synaptic function and autism.
Cell
. 2011 Jul 22;146(2):247–61

14
. Udagawa T, Farny NG, Jakovcevski M, Kaphzan H, Alarcon JM, Anilkumar S, Ivshina M, Hurt JA, Nagaoka K, Nalavadi VC, Lorenz LJ, Bassell GJ, Akbarian S, Chattarji S, Klann E, Richter JD. Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology.
Nat Med
. 2013 Nov;19(11):1473–7

15
. Summarised in
http://www.ncbi.nlm.nih.gov/books/NBK1165/

16
. Jiang H, Mankodi A, Swanson MS, Moxley RT, Thornton CA. Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons.
Hum Mol Genet
. 2004 Dec 15;13(24):3079–88

17
. Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy.
Nat Genet
. 2001 Sep;29(1):40–7

18
. Ho TH, Charlet-B N, Poulos MG, Singh G, Swanson MS, Cooper TA. Muscleblind proteins regulate alternative splicing.
EMBO J
. 2004 Aug 4;23(15):3103–12

19
. Kino Y, Washizu C, Oma Y, Onishi H, Nezu Y, Sasagawa N, Nukina N, Ishiura S. MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1.
Nucleic Acids Res
. 2009 Oct;37(19):6477–90

20
. Hanson EL, Jakobs PM, Keegan H, Coates K, Bousman S, Dienel NH, Litt M, Hershberger RE. Cardiac troponin T lysine 210 deletion in a family with dilated cardiomyopathy.
J Card Fail
. 2002 Feb;8(1):28–32

21
. Reviewed in Michalova E, Vojtesek B, Hrstka R. Impaired pre-messenger RNA processing and altered architecture of 3′ untranslated regions contribute to the development of human disorders.
Int J Mol Sci
. 2013 Jul 26;14(8): 15681–94

22
. For a full description of the syndrome see
http://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathyx-linked-syndrome

23
. Bennett CL, Brunkow ME, Ramsdell F, O’Briant KC, Zhu Q, Fuleihan RL, Shigeoka AO, Ochs HD, Chance PF. A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome.
Immunogenetics
. 2001 Aug;53(6):435–9

24
. For further information see
http://www.alsa.org/

25
. A database of genes believed to be implicated in ALS can be found at
http://alsod.iop.kcl.ac.uk/

26
. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.
Science
. 2009 Feb 27;323(5918):1205–8

27
. Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.
Science
. 2009 Feb 27;323(5918):1208–11

28
. Lai SL, Abramzon Y, Schymick JC, Stephan DA, Dunckley T, Dillman A, Cookson M, Calvo A, Battistini S, Giannini F, Caponnetto C, Mancardi GL, Spataro R, Monsurro MR, Tedeschi G, Marinou K, Sabatelli M, Conte A, Mandrioli J, Sola P, Salvi F, Bartolomei I, Lombardo F; ITALSGEN Consortium, Mora G, Restagno G, Chiò A, Traynor BJ. FUS mutations in sporadic amyotrophic lateral sclerosis.
Neurobiol Aging
. 2011 Mar;32(3):550.e1–4

29
. Sabatelli M, Moncada A, Conte A, Lattante S, Marangi G, Luigetti M, Lucchini M, Mirabella M, Romano A, Del Grande A, Bisogni G, Doronzio PN, Rossini PM, Zollino M. Mutations in the 3′ untranslated region of FUS causing FUS overexpression are associated with amyotrophic lateral sclerosis.
Hum Mol Genet
. 2013 Dec 1;22(23):4748–55

Chapter 17

  
1
. Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R, Shoemaker DD. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays.
Science
. 2003 Dec 19;302(5653):2141–4

  
2
. Reviewed in Keren H, Lev-Maor G, Ast G. Alternative splicing and evolution: diversification, exon definition and function.
Nat Rev Genet
. 2010 May;11(5):345–55

  
3
. These steps are laid out very clearly in some reviews e.g. Wang GS, Cooper TA. Splicing in disease: disruption of the splicing code and the decoding machinery.
Nat Rev Genet
. 2007 Oct;8(10):749–61

  
4
. More information on the spliceosome can be found in e.g. Padgett RA. New connections between splicing and human disease.
Trends Genet
. 2012 Apr;28(4):147–54

  
5
.
http://ghr.nlm.nih.gov/condition/retinitis-pigmentosa

  
6
. Vithana EN, Abu-Safieh L, Allen MJ, Carey A, Papaioannou M, Chakarova C, Al-Maghtheh M, Ebenezer ND, Willis C, Moore AT, Bird AC, Hunt DM, Bhattacharya SS. A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11).
Mol Cell
. 2001 Aug;8(2):375–81

  
7
. McKie AB, McHale JC, Keen TJ, Tarttelin EE, Goliath R, van Lith-Verhoeven JJ, Greenberg J, Ramesar RS, Hoyng CB, Cremers FP, Mackey DA, Bhattacharya SS, Bird AC, Markham AF, Inglehearn CF. Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13).
Hum Mol Genet
. 2001 Jul 15;10(15):1555–62

  
8
. Chakarova CF, Hims MM, Bolz H, Abu-Safieh L, Patel RJ, Papaioannou MG, Inglehearn CF, Keen TJ, Willis C, Moore AT, Rosenberg T, Webster AR, Bird AC, Gal A, Hunt D, Vithana EN, Bhattacharya SS. Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa.
Hum Mol Genet
. 2002 Jan 1;11(1):87–92

  
9
. Maita H, Kitaura H, Keen TJ, Inglehearn CF, Ariga H, Iguchi-Ariga SM. PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa, is a splicing factor.
Exp Cell Res
. 2004 Nov 1;300(2):283–96

10
. Microcephalic osteodysplastic primordial dwarfism type 1 also known as Taybi-Linder syndrome.
http://rarediseases.info.nih.gov/gard/5120/microcephalic-osteodysplastic-primordial-dwarfism-type-1/resources/1