Junk DNA: A Journey Through the Dark Matter of the Genome

Index

11-FINGERS protein 178–9, 286

AAUAAA motif 233–4

Adam and Eve story 125

addiction 265

age, as health risk factor 59–62

Agouti viable yellow mouse 122

AIDS 38, 41, 244, 279

albinism 211

alcohol 265, 266

Alnylam (company) 274–6

alpha satellite repeats 66

Alzheimer’s disease 76, 110–11, 212, 329

amino acids 10

adding to protein chain 146–9

placeholders for 14, 15

Amish communities 27, 243, 258

amyotrophic lateral sclerosis (ALS) 235–6, 276

aneuploidy 74–5

Angelman syndrome 137–40, 142, 329

antibiotics 152–3

antibodies 172–3, 271–2

anti-obesity drugs 215, 218

antisense RNAs 271, 276–81

aplastic anaemia 56–7, 58, 329

apoliprotein B100 280

apoptosis 50

appendix 32

assisted reproductive technologies 141–3

AUG sequence 224, 226

autosomes 80

BACE1 enzyme 111

bacteria 149, 152–3, 237

Barr body 84, 120

basal cell carcinoma 226, 329

bases 13

Beckwith-Wiedemann syndrome 140, 142, 329

beta-amyloid 111

biomarkers 217–18

BK protein 265

blindness 272

blood cancer 118, 217

blood pressure, high 263

blood stem cells 54, 58

body mass index 214

Boleyn, Anne 202

bone marrow 259, 260

brain

genes never expressed 176

long RNAs and 110–12

smallRNAs and 263–7

brain tumours

childhood 276–7

ETMR paediatric 330

BRCA1 gene 108

breast cancer 74, 108, 118, 217, 268, 272

brittle bone disease 219–25, 332

Brown, Louise 141

Burkitt’s lymphoma 48, 158–9, 172–3, 329

bystander events 101

CAC sequences 245

CAG sequences 245

calico cats 94–5

cancer 329–30

aneuploidy and 74–5

long RNAs and 107–10, 118–19

major repressor and 118–19

obesity and 62

paclitaxel and 74

promoters and 158–9

smallRNAs and 265–8

super-enhancers and 167

tailored therapies 27

tumour suppression 275

see also individual diseases

cancer cells, telomerase activity 53

carbon monoxide levels 214

cardiac hypertrophy 263

cardiac muscle 262–3

cardiovascular disease 60, 77, 246, 265, 279

cartilage-hair hypoplasia 257–8, 330

cats

with extra toes 203–4

tortoiseshell/calico patterning 94–5

CCG repeats 10, 19, 123, 227

Celera Genomics (company) 25, 29

cells 14

division 63–6

CENP-A protein 66–73

centromeres 64–73, 80

CGG repeats 226

Charcot-Marie-Tooth disease 44

chloride transport 231

cholesterol 279–80

chromosome 4 283–4, 286

chromosome 8 158

chromosome 10 208

chromosome 11 141

chromosome 13 77–8

chromosome 14 142, 158

chromosome 15 138–40

chromosome 16 215

chromosome 18 77–8

chromosome 21 76, 77–8

chromosomes

numbers 80

repair 47–9

chronic psychological stress 61

cigarette smoke, exposure to 213–14

cigarette smoking 58–9, 61

cirrhosis of the liver 213–14

cleft lip 204

Clinton, Bill 25

cloning 95–6

cocaine 265

collagens, defects in 220

colorectal cancer 108

congenital diarrhoea disorder 243–4, 330

consanguinity 207–8

Cornelia de Lange syndrome 169, 330

CpG motifs 114, 123, 133–4

cross-talk 117–23, 131–2, 191

crossing-over 43–4

CTCF protein (11-FINGERS) 178–9, 286

CTG repeats 9, 21, 23–4, 230

CUG repeats 230

cystic fibrosis 26–7

cytomegalovirus (CMV) 278

cytoplasm 15, 146

daughter cells 4

de novo mutation 138

detoxification 275–6

Dexter, Michael 26

diabetes

in babies 207

genetics contribution in 212

type 1 234

type 2, obesity and 61–2, 215

Diamond-Blackfan Anaemia 150

diarrhoea 243–4

Dicerna (company) 281

diet, and longevity 62

DNA

compaction/looping 168–70

knitting with 9–11

DNA double helix 68

DNA fingerprinting 45–6

DNA methylation 114–16

DNA methyltransferases 134

dominant disorders 8

Down’s Syndrome 76–7, 79, 80, 330

Duchenne muscular dystrophy 26–7, 91–4, 248–54, 276, 278, 330

DUX4 (FSHD retrogene) 284–6

dwarfism 243, 258, 331

dyskeratosis congenita 55–6, 330

dystrophin 92–3, 248–54, 278

Edward’s syndrome 77, 79, 80, 330

eggs

chromosome numbers 64, 80

formation 43–4, 64, 73, 75, 181–2

mutated cells 138

electron transport chain 154

embryonic stem (ES) cells 105, 163–6

ENCODE project 185–99

critiques 191–2, 196–9

evolutionary conclusions 195–9

measures of function 191–4

multiple parameters 188–91

endogenous retroviruses (ERVs) 41–3

enhancers 159–60

epigenetic modifications and 160–7

epigenetic modifications 114

and enhancers 160–7

self-sustaining 176

smallRNAs and 267

epigenetic systems 115

cross-talk with long non-coding RNAs 117–23, 131–2

and expansions 123

erythromycin 152

ETMR paediatric brain tumour 330

evolution, ENCODE project and 195–9

exons 238, 249–50

expressivity, variable 206

extra digits 202–4, 330

extracellular matrix 50–1

EZH2 enzyme 117

facial development 204–7

facioscapulohumeral muscular dystrophy (FSHD) 11–12, 283–6, 330

factories 171–3

familial hypercholesterolaemia 279–80

Feingold syndrome 257, 330

fibrillarin 152

fibroblasts 50–1

fingers, extra 202–4, 330

forebrain 264

FOXP3 transcription factor 234

Fragile X protein 20, 227–9

Fragile X syndrome 10, 19–20, 89, 123, 227, 229–30, 330

frame shift 250

Friedreich’s ataxia 11, 18–19, 20, 331

fruit flies, HOX cluster 41

FSHD 11–12, 283–6, 330

FTO gene 215

FUS gene 236

GAA repeats 11, 18–19

gain-of-function mutations 230

gametes

creation 64, 65, 75–6

see also eggs; sperm

GATA8 transcription factor 207

Gcn5 gene 50

gender, determination 81–2

gene expression

amplification steps 14–16

levels 159–60

stochastic component 88–9

genes, protein-coding, identification 98

genome percentage having function 186–7

potential versus actual functional regions 191–4

see also human genome genome-wide association studies (GWAS) 213

Genzyme (company) 280

germ cells 64

telomerase activity 53

germline 133, 285

GGC sequences 246–7

GGT sequences 246–7

GlaxoSmithKline (company) 252–4

glioblastoma 107

glutamine 245

glycine 246, 247

GU sequences 244

haemoglobin, production 115, 172, 176

haemophilia B 90

Hawking, Stephen 235

heart attacks 262

heart disease, obesity and 61

heart protein 231–2

height 184

Hemingway, Ernest 203–4

hepatitis C virus 269, 331

HHV-8 virus 244–5, 331

histidine 245

histone proteins 69–70, 73

modifications 113–20

HIV 41, 244, 279

holoprosencephaly 204–7, 331

horses 268

HOX genes 41, 106, 175

human cartilage-hair hypoplasia 257–8, 330

human genome

number of genes 28–9

percentage having function 186–7

potential versus actual functional regions 191–4

size 29–32

Human GenomeProject 12, 26

human genome sequence cost of sequencing 27

initial draft 25

human immunodeficiency virus (HIV) 41, 244, 279

human telomere syndromes 55

Huntington’s disease 212, 213

Hutchinson-Gilford Progeria 245–6, 331

hydatidiform mole 126–8

idiopathic pulmonary fibrosis 56, 331

IFITM5 gene 223

Ig genes 175

immune system 115, 172–3, 257–8, 269, 285

immunologically privileged sites 285

imprinting 128–30

disorders 136–41, 142–3

resetting the imprint 133–6

imprinting control element (ICE) 130–5, 139–40

induced pluripotent stem (iPS) cells 164

infection, risk in elderly 54

infertility treatment 141–3

inflammatory response 160

insulation theory 34–6

insulators 177–9

insulin 207, 231–2, 234, 271

interspersed repetitive elements 38–41

intestines 260–1

introns 17, 214, 238, 249

IPEX syndrome 234–5, 331

iron overload 19

IRX3 gene 216

Isis (company) 280

Japan, diet and longevity 62

Jolie, Angelina 108

Kaposi’s sarcoma 244–5

karyotypes 81

keratin 176

Klinefelter’s syndrome 332

Kynamro (drug) 280

Leopold, Prince 90

limb development 41, 106, 204

linc RNAs 103

lipoproteins 280

liver, and detoxification 275–6

liver cancer 108, 275–6

liver cirrhosis 213–14

long non-coding RNAs 97–112

3D structures 99–100

and brain 110–12

and cancer 107–10, 118–19

cross-talk with epigenetic systems 117–23, 131–2

definition 97

enhancing 162, 167

expression level 97–8

expression patterns 190

functions 102–3, 106, 112

longevity 60–2

Lou Gehrig’s disease (amyotrophic lateral sclerosis) 235–6, 276

lung cancer 74, 107, 217, 268

macromolecular complex 146

major repressor 117–20

and cancer 118–19

knockout of 132

malignant melanoma see melanoma

mammals, reproduction 125–6, 129–30

marsupials, imprinted genes 130

master regulators 164–6

MeCP2 gene 91

Mediator complex 162–3, 165, 167, 169

melanoma 35, 226, 331

Merck (company) 281

messenger RNA 16, 147–9, 222–4

expression level 97–8

expression patterns 190

untranslated regions at end of 232–6

see also splicing

methionine 247

mice

Agouti viable yellow 122

brain 263–5

with Fragile X syndrome 229

gene knockout experiments 260–1

imprinted genes 135

long non-coding RNAs 98

overweight 215–16

reconstituted eggs experiments 126–8, 135

repeat elements in 40

microRNA (miRNA) 256

Mipomersen (drug) 280

Mirna Therapeutics (company) 275–6

mitochondria 153–5

mutant 155

monotremes 132

morphogens 202–4

and facial development 204–7

and pancreas 207–10

mosquitoes 268

motor neuron disease (amyotrophic lateral sclerosis) 235–6, 276

multiple sclerosis 212

muscle stem cells 261–2

muscle wasting 232

Muscleblind-like protein 1 (MBNL1) 230

mutations

de novo 138

definition 8

effects 10

gain-of-function 230

MYC protein 158

myotonic dystrophy 8–9, 21–4, 230–2, 331

National Institutes of Health 25

neurons 20, 114–15, 228–9, 263

neuropathic pain 111–12, 331

non-templated changes 235

North American eastern equine encephalitis virus 268–9, 331

Novartis 281

nucleolus 150–1

obesity 61–2, 214–17

OCA2 gene 211

octamers 69–73

Ohio Amish dwarfism 243, 331

Opitz-Kaveggia syndrome 163, 331

organ transplants 42

organismal complexity, proportion of junk DNA and 4, 187–8

osteogenesis imperfecta (brittle bone disease) 219–25, 332

ovarian cancer 74, 107, 268

paclitaxel (drug) 74

pancreas, development 209

pancreatic agenesis 207–10, 332

pancreatic cancer 108

papillary thyroid cancer 108

parent-of-origin effect 128, 138, 140

Patau’s Syndrome 77, 79, 80, 332

patient-derived cells 165

penetrance, variable 206

personalised medicine 217–18

pigmentation 211, 214

pigs 42–3

placebo procedures 252–3

placenta 105, 127, 129–30, 135, 141

plaques 111

plasmapheresis 279

pluripotency 105–6, 107

poetry example 238–40

polyadenylation signal 233, 234–5

Polycomb Response Complex (PRC2) 118

positive feedback loops 166

Prader-Willi syndrome 136–40, 150, 152, 332

pregnancy rates 78

programmed cell death 50

promoters 157–9, 190

and cancer 158–9

Prosensa (company) 252, 254

prostate cancer 107, 108, 109, 118–19

proteins

as drugs 271–2

functions 10

importance 1

pseudoautosomal regions 182

PTF1A transcription factor 207

pufferfish 32–3

pulmonary fibrosis 56, 58–9

RaNA Therapeutics (company) 281

red blood cells 54

red — green colour blindness 90

regulatory regions 170, 189, 195, 207, 209–11

regulatory T cells 234

research funding 198–9

retina, viral infection in 278–9

retinitis pigmentosa 242–3, 332

retrogenes 284–6

Rett syndrome 90–1

rheumatoid arthritis 212, 271

ribosomal RNA molecules see rRNA

ribosomes 146–7, 148–9, 224–5, 245

in primitive organisms 151

RNA 15–16

enzymatic activities 156

Roberts Syndrome 169, 332

Roche (company) 281

rodents, repeat elements in 40

Romanov dynasty 90

rRNA 146–9

methylation 151

mutations in genes 149

numbers of genes 149

Sainsbury, David 26

Sanofi 280

Sarepta 254

satellite cells 261

schizophrenia 212, 213

scissors enzyme 258, 260–3, 264–5

senescence 51

sense RNAs 277–8

sex chromosomes 80

Silver-Russell syndrome 140, 142, 332

simple sequence repeats 45–6

Six3 transcription factor 205

skeletal deformations 108, 119, 224, 257–8

skeletal muscle problems 231–2, 261

skin cells 168

small interfering RNA (siRNA) 256

small molecule drugs 271–3

smallRNAs 255–69

and brain 263–7

and cancer 265–8

epigenetic modifications 267

and stem cells 258–63

smell, sense of 263–4

SMN1 gene 248

SMN2 gene 248

smoking 58–9, 61

passive 214

snoRNAs 150–2

Sonic Hedgehog (SHH) protein 202

sperm

chromosome numbers 64, 80

formation 43–4, 64, 73, 75–6, 181–2

mutated cells 138

Spinal Muscular Atrophy 247–8, 332

spindle apparatus 65–6, 67, 70–1, 73–4

spleen 260

spliceosome 241–2, 243, 244, 248

splicing 17, 30, 222, 237–54

alternative 238

and disease 242–8

manipulating for therapeutic gain 248–54

SRY gene 82

statins 279

stem cells 53–4

blood 54, 58

smallRNAs and 258–63

stop signals 148–9, 245, 246, 250

super-enhancers 163, 165–7

and cancer 167

supratentorial neuroectodermal tumours 266

telomerase activity 52–3

telomeres 49–62

and diseases 55–9

length importance 54–5

as molecular clock 60–2

shortening 51–3

testes 82, 110

testosterone 82, 109

tetracycline 152

tetrapods 99

thymus 260

thyroid gland 234

tobacco 58, 61

tortoiseshell cats 94–5

totipotency 105

Trading Places (film) 47

transcription factors 157–9, 205

transfer RNA see tRNA transthyretin 274

Treacher-Collins Syndrome 150

trisomy 13 77–8

trisomy 18 77–8

trisomy 21 76, 77–8

tRNA 147–9

and insulation 179–80

numbers of genes 150

Tsix gene 87–8

Tsix RNA 87–8, 97

TTAGGG motifs 49, 52, 54

tumour suppressors 275

Turner’s syndrome 332

two-base sequences 241

ultraviolet radiation 35

uniparental disomy 138

untranslated regions (UTRs) 222–3, 226–7, 230, 232–6

variable expressivity 206

variable penetrance 206

Victoria, Queen 90

virgin birth 125

Wellcome Trust 25, 26

white blood cells 60–1, 268–9

Williams-Beuren syndrome 44

worms

genome size 29–32

number of genes 28

X chromosomes 79–96, 180–4

people with wrong numbers of 83, 180–1, 183–4

physical conformation 83–4

X inactivation 82–4, 86–8, 89, 93–6, 120–1, 180–3

X inactivation centre 84, 88

X0 syndrome 332

xenotransplantation 42–3

Xist gene 84–8

Xist RNA 85–8, 94, 97, 120, 182

XXX syndrome 332

XXY syndrome 332

Y chromosome 80–1, 181–3

yeast, genome size 31–2

zebrafish 98

zygote 64, 104–5