Junk DNA: A Journey Through the Dark Matter of the Genome (42 page)

22
. For a useful description see
http://www.patient.co.uk/doctor/aplastic-anaemia

23
. de la Fuente J, Dokal I. Dyskeratosis congenita: advances in the understanding of the telomerase defect and the role of stem cell transplantation.
Pediatr Transplant
. 2007 Sep;11(6):584–94

24
. Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.
Proc Natl Acad Sci U S A
. 2005 Nov 1;102(44):15960–4

25
.
http://www.who.int/mediacentre/factsheets/fs339/en/

26
. Alder JK, Guo N, Kembou F, Parry EM, Anderson CJ, Gorgy AI, Walsh MF, Sussan T, Biswal S, Mitzner W, Tuder RM, Armanios M. Telomere length is a determinant of emphysema susceptibility.
Am J Respir Crit Care Med
. 2011 Oct 15;184(8):904–12

27
. Cited in Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing.
Nature
. 2010 Mar 25;464(7288):520–8

28
. Statistical factsheet from the American Heart Association on Older Americans & Cardiovascular Diseases, 2013 update

29
.
http://www.rcpsych.ac.uk/healthadvice/problemsdisorders/depressioninolderadults.aspx

30
. Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, Aviv A, Spector TD. Obesity, cigarette smoking, and telomere length in women.
Lancet
. 2005 Aug 20–26;366(9486):662–4

31
. Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older.
Lancet
. 2003 Feb 1;361(9355):393–5

32
. Fitzpatrick AL, Kronmal RA, Kimura M, Gardner JP, Psaty BM, Jenny NS, Tracy RP, Hardikar S, Aviv A. Leukocyte telomere length and mortality in the Cardiovascular Health Study.
J Gerontol A Biol Sci Med Sci
. 2011 Apr;66(4):421–9

33
. Atzmon G, Cho M, Cawthon RM, Budagov T, Katz M, Yang X, Siegel G, Bergman A, Huffman DM, Schechter CB, Wright WE, Shay JW, Barzilai N, Govindaraju DR, Suh Y. Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians.
Proc Natl Acad Sci U S A
. 2010 Jan 26;107 Suppl 1:1710–7

34
. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry.
Psychol Bull
. 2004 Jul;130(4):601–30

35
. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress.
Proc Natl Acad Sci U S A
. 2004 Dec 7;101(49):17312–5

36
.
http://www.who.int/mediacentre/factsheets/fs311/en/index.html

37
. For a useful introduction to this field, see Tennen RI, Chua KF. Chromatin regulation and genome maintenance by mammalian SIRT6.
Trends Biochem Sci
. 2011 Jan;36(1):39–46

38
. Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, Aviv A, Spector TD. Obesity, cigarette smoking, and telomere length in women.
Lancet
. 2005 Aug 20–26;366(9486):662–4

39
. UNFPA report on Ageing in The Twenty-First Century, 2012

40
. Jennings BJ, Ozanne SE, Dorling MW, Hales CN. Early growth determines longevity in male rats and may be related to telomere shortening in the kidney.
FEBS Lett
. 1999 Apr 1;448(1):4–8

Chapter 6

  
1
. From
The King and I
, 1956, screenplay by Ernest Lehman, 20th Century Fox

  
2
. A good overview of the types of centromeres in the different arms of the evolutionary tree can be found in Ogiyama Y, Ishii K. The smooth and stable operation of centromeres.
Genes Genet Syst
. 2012;87(2):63–73

  
3
. For a useful review, see Verdaasdonk JS, Bloom K. Centromeres: unique chromatin structures that drive chromosome segregation.
Nat Rev Mol Cell Biol
. 2011 May;12(5):320–32

  
4
. Palmer DK, O’Day K, Wener MH, Andrews BS, Margolis RL. A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones.
J Cell Biol
. 1987 Apr;104(4):805–15

  
5
. Takahashi K, Chen ES, Yanagida M. Requirement of Mis6 centromere connector for localizing a CENP-A-like protein in fission yeast.
Science
. 2000 Jun 23;288(5474):2215–9

  
6
. Blower MD, Karpen GH. The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions.
Nat Cell Biol
. 2001 Aug;3(8):730–9

  
7
. Hori T, Amano M, Suzuki A, Backer CB, Welburn JP, Dong Y, McEwen BF, Shang WH, Suzuki E, Okawa K, Cheeseman IM, Fukagawa T. CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore.
Cell
. 2008 Dec 12;135(6):1039–52

  
8
. Heun P, Erhardt S, Blower MD, Weiss S, Skora AD, Karpen GH. Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores.
Dev Cell
. 2006 Mar;10(3):303–15.

  
9
. Van Hooser AA, Ouspenski II, Gregson HC, Starr DA, Yen TJ, Goldberg ML, Yokomori K, Earnshaw WC, Sullivan KF, Brinkley BR. Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A.
J Cell Sci
. 2001 Oct;114(Pt 19):3529–42

10
. Zuccolo M, Alves A, Galy V, Bolhy S, Formstecher E, Racine V, Sibarita JB, Fukagawa T, Shiekhattar R, Yen T, Doye V. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions.
EMBO J
. 2007 Apr 4;26(7):1853–64

11
. Palmer DK, O’Day K, Wener MH, Andrews BS, Margolis RL. A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones.
J Cell Biol
. 1987 Apr;104(4):805–15

12
. Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres.
Nature
. 2010 Sep 16;467(7313):347–51

13
. Warburton PE, Cooke CA, Bourassa S, Vafa O, Sullivan BA, Stetten G, Gimelli G, Warburton D, Tyler-Smith C, Sullivan KF, Poirier GG, Earnshaw WC. Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres.
Curr Biol
. 1997 Nov 1;7(11):901–4

14
. For a very good analysis of this model, see Sekulic N, Black BE. Molecular underpinnings of centromere identity and maintenance.
Trends Biochem Sci
. 2012 Jun;37(6):220–9

15
. If you are interested in learning more about the details of this process, and the epigenetic modifications involved, see González-Barrios R, Soto-Reyes E, Herrera LA. Assembling pieces of the centromere epigenetics puzzle.
Epigenetics
. 2012 Jan 1;7(1):3–13

16
. From the song ‘Something Good’ in the movie version of
The Sound of Music
, 1965, 20th Century Fox

17
. A particularly important protein in this respect is call HJURP, and more information can be found in Sekulic N, Black BE. Molecular underpinnings of centromere identity and maintenance.
Trends Biochem Sci
. 2012 Jun;37(6):220–9

18
. Palmer DK, O’Day K, Margolis RL. The centromere specific histone CENP-A is selectively retained in discrete foci in mammalian sperm nuclei.
Chromosoma
. 1990 Dec;100(1):32–6

19
. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol.
Nature
. 1979 Feb 22;277(5698):665–7

20
.
http://www.cancerresearchuk.org/cancer-help/about-cancer/treatment/cancer-drugs/paclitaxel

21
. Figure quoted in Rajagopalan H, Lengauer C. Aneuploidy and cancer.
Nature
. 2004 Nov 18;432(7015):338–41

22
. For a review of this issue, see Pfau SJ, Amon A. Chromosomal instability and aneuploidy in cancer: from yeast to man.
EMBO Rep
. 2012 Jun 1;13(6):515–27

23
. Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BS, Kingsbury MA, Cabral KM, McConnell MJ, Anliker B, Fontanoz M, Chun J. Constitutional aneuploidy in the normal human brain.
J Neurosci
. 2005 Mar 2;25(9):2176–80

24
. Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J. Chromosomal variation in neurons of the developing and adult mammalian nervous system.
Proc Natl Acad Sci U S A
. 2001 Nov 6;98(23):13361–6

25
. Kingsbury MA, Friedman B, McConnell MJ, Rehen SK, Yang AH, Kaushal D, Chun J. Aneuploid neurons are functionally active and integrated into brain circuitry.
Proc Natl Acad Sci U S A
. 2005 Apr 26;102(17):6143–7

26
. Melchiorri C, Chieco P, Zedda AI, Coni P, Ledda-Columbano GM, Columbano A. Ploidy and nuclearity of rat hepatocytes after compensatory regeneration or mitogen-induced liver growth.
Carcinogenesis
. 1993 Sep;14(9):1825–30

27
. For an extraordinary account of the ill-tempered controversy over who exactly identified the cause of Down’s Syndrome, which is still raging after 50 years, see
http://www.nature.com/news/down-s-syndrome-discovery-dispute-resurfaces-in-france-1.14690

28
. For more information on the medical and social aspects of Down’s Syndrome there are a large number of patient advocacy groups such as
http://www.downs-syndrome.org.uk/

29
.
http://www.nhs.uk/conditions/edwards-syndrome/Pages/Introduction.aspx

30
.
http://www.cafamily.org.uk/medical-information/conditions/p/patau-syndrome/

31
. Toner JP, Grainger DA, Frazier LM. Clinical outcomes among recipients of donated eggs: an analysis of the U.S. national experience, 1996–1998.
Fertil Steril
. 2002 Nov;78(5):1038–45

Chapter 7

  
1
. Statistical Bulletin from the Office for National Statistics, 8 August 2013 Annual Mid-year Population Estimates, 2011 and 2012

  
2
. The publication that demonstrated the importance of this gene is Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M. Genetic evidence equating SRY and the testis-determining factor.
Nature
. 1990 Nov 29;348(6300):448–50