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148
INDEX
comparative genome hybridization (CGH),
6–7
complement activation, 92
compound cluster, 23
congenital thymic aplasia, 96
conservative substitutions, 50
conservative transposition, 27
core promoter sequence, 39
cosmid vectors, 109
creatine phosphokinase, 51
Cre-loxP recombination system, 117
crossover, 17
cyclin-dependent protein kinases (Cdks), 68
cyclins, 68–9
cytokines, 87–8
activities, 88t
chemokines, 87
properties, 87
receptors, 87
cytokinesis, 68
cytosine, deamination of, 13
cytotoxicity, 92
D
D arm, 37
deamination, 13
deletion polymorphism, 57
deoxyribonucleoside 5’-triphosphates, 10
deoxyribonucleoside triphosphates, 104f, 105
depurination, 13
diabetic embryopathy, 131
dideoxyribonucleoside triphosphates, 104f, 105
differential display PCR, 113
DiGeorge syndrome, 96, 126f, 127–8
diploid, 66
disjunction, 17–9
DNA, 1–8
base composition, 8
chemical environment, 8
chemical modification of, 25
denaturation, 8
double helix, 2
melting curve, 8
noncoding, 25–8
microsatellite DNA, 25–6
minisatellite DNA, 25–6
satellite DNA, 25
transposons, 26–8
polynucleotide chain, 2f
supercoiling, 11
topoisomerases, 11–2
DNA cloning, 108f, 109–11, 112f
DNA damage, 12–3
DNA polymerases, 11
DNA primase, 11
DNA repair, 13, 72–3
DNA sequencing, 104f, 105, 131
DNA-binding proteins, 41–3
helix-loop-helix protein, 43
homeodomain proteins, 41
leucine zipper proteins, 42
zinc finger proteins, 43
DNA-binding transcription factor, 132
downstream sequences, 33
Duchenne muscular dystrophy (DMD), 51
dwarfism, 41
dynamic mutations, 53–5
dystrophin, 51
E
early instability theory, 72
EcoR1 enzyme, 100f, 101
electrophoresis, 102f, 103
ELISA test, 122f, 123
encephalopathy, 32
endocytosis, receptor-mediated, 136
endogenous antigens, 83
immune response to, 86–7
enhancer sequences, 39
enzyme-linked immunoabsorbent assay (ELISA) test,
122f, 123
eosinophil chemotactic factor, 79
eosinophils, 78
epigenetic control, 23, 25
episomes, 134, 135–6
euchromatin, 5, 10
ex vivo gene therapy, 134
exogenous antigens, 83
early response to, 85
late response to, 85–6
exons, 23
expression vector, 114f, 115
EYA1 protein, 131
F
familial adenomatous polyposis coli (FAPC), 64
flow cytometry, 126f, 127
fluorescence in situ hybridization (FISH), 6
FOS protein, 42
fragile X syndrome, 54
frameshift mutations, 51
G
G banding, 5–6
G
0
(gap) phase, 66
G
1
checkpoint, 66, 68
G
1
phase, 66
G
2
checkpoint, 66, 69
G
2
phase, 66
gain of function mutation, 55–6
gatekeeper tumor-suppressor genes, 60, 62t
gene expression, 39–48
definition of, 115
mechanisms of, 39–40, 41f, 44–6
cis-acting DNA sequences, 39–40
trans-acting proteins, 40
gene knockout, 116f, 117
gene regulatory proteins, 40
gene superfamily, 23
gene therapy, 133–6
episomes, 134
ex vivo, 134
germ-line, 133
host cell chromosomes, 134
nonviral vectors, 135–6
direct injection, 135
liposomes, 135
receptor-mediated endocytosis, 135
somatic cell, 133
viral vectors, 134–5
adeno-associated, 135
adenoviral, 135
herpes simplex, 135
lentivirus, 135
oncoretroviral, 134
in vivo, 134
genes
cluster, 23
dispersed, 23
multiple clusters, 23
truncated, 23
genetic code, 137t
genetic diseases, chromosomal locations of,
139–45
genetic recombination, 18f
general recombination, 19
site-specific, 19
genomic imprinting, 25
germ-line gene therapy, 133
growth factors, 60t
gyrases, 12
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INDEX
H
haploid, 66
helix-loop-helix protein, 43
hematopoietin, 87
hemophilia B, 115
hemopoietic stem cells, 81, 83
heparins, 79
hereditary cancer syndromes, 62–5
BRCA1 and BRCA2 hereditary breast cancers, 65
development of, 71
familial adenomatous polyposis coli, 64
Li-Fraumen syndrome, 63
neurofibromatosis type 1, 63–4
retinoblastoma, 62–3
hereditary nonpolyposis colorectal cancer (HNPCC), 15
herpes simplex viruses, 135
heterochromatin, 4, 10
HindIII enzyme, 100f, 101
histamine, 79
histiocytes, 80
histone methyltransferase, 129
histones, 3
chemical modification of, 25
positively charged, 121
homeobox sequence, 41
homeodomain proteins, 41
host cell chromosomes, 134
housekeeping genes, 39–48
housekeeping proteins, 39–48
hsp70, 40
human disease gene identification, 129–32
chromosome abnormality, 129
comparison of human and mouse maps, 131–2
DNA sequencing, 131
transcript mapping, 130
human Factor IX, 115
human Factor VIII, 109
human genetic diseases, chromosomal locations of,
139–45
human immunodeficiency virus (HIV)
ELISA test, 122f, 123
structure, 122f, 123
Western blot test, 122f, 123
Huntington disease, 54–5
hypermutation, 82
I
IgA, 91–2
IgD, 91
IgE, 91
IgG, 91
IgM, 90–1
immune system, 77–99
cell biology of, 77–88
clonal selection theory, 89
disorders of phagocytic function, 96–7
molecular biology of, 89–99
organ-specific autoimmune disorders,
97–9
systemic autoimmune disorders, 97
immunoglobulin (IG), 89–92
agglutination, 92
complement activation, 92
cytotoxicity, 92
gene rearrangement, 90
heavy chains, 89
insertional diversity, 90
junctional diversity, 90
light chains, 89
neutralization, 92
opsonization, 92
properties, 93
somatic cell mutations, 90
in vivo gene therapy, 134
insertion polymorphism, 57
insulator sequences, 39
interleukin, 88t
internal gene fragments, 23
introns, 23, 50
inverse PCR, 113
isotype switching, 82
J
JUN protein, 42
K
karyotype chaos, 71
Kearns-Sayre syndrome (KS), 31–2
L
lac operon, 46–7
lactic acidosis, 32
Leber’s hereditary optic neuropathy (LHON), 31–2
lentiviruses, 135
leucine zipper proteins, 42
leukotrienes, 79
Li-Fraumen syndrome (LFS), 63
ligase chain reaction (LCR), 124f, 125
liposomes, 135
long interspersed nuclear elements (LINEs), 26
long terminal repeat transposons, 26
loss of function mutation, 55
M
macrophages, 80
Martin-Bell syndrome, 54
mast cells, 78–9
maternal RNA, 45–6
meiosis, 19–20
vs. mitosis, 21t
meiosis I, 17–9
alignment, 17
cell division, 17–9
crossover, 17
disjunction, 17–9
synapsis, 17
meiotic chromosomes, 5
Mep-1, 40
metaphase, 5, 68
micro RNA (miRNA) genes, 24, 44
microsatellite DNA, 25–6
microsatellite DNA polymorphism, 57
microsatellite instability, 72–3
Miller syndrome, 131
minisatellite DNA, 25–6
minisatellite DNA polymorphism, 57
mismatch repair, 13
missense mutations, 50
mitochondrial diseases, 31–2
mitochondrial genome, 29–32
general features, 29
location of mtDNA genes and gene products, 30f
protein-coding genes, 29, 30t
RNA-coding genes, 29, 30t
mitochondrial myopathy, encephalopathy, lactic acidosis, and
stroke-like episodes syndrome (MELAS), 32
mitochondrial proteins, 31
mitosis, 66–8
vs. meiosis, 21t
mitotic chromosomes, 5
modified standard theory of cancer, 71
molecular biology techniques, 100–28
DNA cloning, 108f, 109–11, 112f
DNA sequencing, 104f, 105
polymerase chain reaction, 113–28
restriction enzymes, 100–4
monocytes, 79–80
multiple myeloma, 97–8
multiple sclerosis, 98–9
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mutagenesis, 116f, 117
mutations, 49–57
base substitutions, 49
cancer progression and, 72–3
gain of function, 55–6
general features, 49
loss of function, 55
non-silent (nonsynonymous) mutations, 50–4
dynamic mutations, 53–5
frameshift mutations, 51
missense mutations, 50
nonsense mutations, 50
RNA splicing mutations, 52
translocation mutations, 52–3
transposon mutations, 52
point, 58
silent (synonymous), 49–50
translocation, 58–9
myasthenia gravis, 99
MYC protein, 42
myeloperoxidase deficiency (MPO), 96
myoclonic epilepsy with ragged red fibers syndrome
(MERRF), 31
MyoD protein, 42
N
Nager syndrome, 131
natural killer CD16
cells, 81
negative selection, 83
negative supercoiling, 11
neurofibromatosis type 1, 63–4
neutralization, 92
neutrophils, 77
nitrogenous bases, 1
noncoding DNA, 25–8. See also DNA
microsatellite DNA, 25–6
minisatellite DNA, 25–6
satellite DNA, 25
transposons, 26–8
nonconservative substitutions, 50
nonsense mutations, 50
Northern blot, 118f, 119
NSD1 protein, 129
nuclear genome, 22–8
epigenetic control, 25
general features, 22–3
noncoding DNA, 25–8
protein-coding genes, 23–4
nucleic acids, 1
nucleosides, 1
nucleosome, 3
nucleotide excision repair, 13
O
oncogenes. See also proto-oncogenes
alteration of proto-oncogenes to, 58–9
definition of, 58
oncogenesis, 71–2
all-aneuploidy theory, 72
early instability theory, 72
formation of cancer stem cells, 72
modified standard theory, 71
standard theory, 71
oncoretroviruses, 134
opsonization, 92
organ-specific autoimmune disorders, 97–9
P
P1 artificial chromosomes (P1 artificial chromosomes), 109
palindromes, 100f, 101
PAX3 gene, 131–2
petit arms, 7
Philadelphia chromosome, 58
phosphates, 1
pituitary dwarfism, 41
plasmid vector, 109
point mutation, 58
polymerase chain reaction (PCR), 113–28
chimeric mice, 116f
differential display, 113
ELISA test, 122f, 123
expression vector, 114f, 115
flow cytometry, 126f
gene knockout, 116f, 117
inverse, 113
ligase chain reaction, 124f, 125
mutagenesis, 116f, 117
Northern blot, 118f, 119
real-time, 113
reverse transcription, 113
viral detection, 112f, 113
Western blot, 120f, 121
polymorphisms, 49
positive selection, 83
positive supercoiling, 11
prenatal testing, 106f, 107
processed pseudogenes, 23
prometaphase, 5, 66
prophase, 66
protein synthesis, 33–8
general features, 33
processing RNA transcript into mRNA, 34–5
transcription, 33–4
translation, 35–7
protein-coding genes, 23–4
proto-oncogene, 58–60
proto-oncogenes
alteration to oncogene, 58–9
amplification, 58
definition of, 58
growth factors, 60t
point mutation, 58
RAS, 59
receptors, 60t
signal transducers, 60t
transcription factors, 60t
translocation, 58
proximal promoter region sequence, 39
pseudogenes, 23–4
purines, 1
pyrimidine, 1
Q
Q banding, 6
queue arm, 7
R
R banding, 6
RAS gene, 59
RB1 gene, 61
real-time PCR, 113
receptors, 60t
recombinant plasmid, 109
regulatory RNA genes, 24
repetitive DNA sequences, 23
replication, 9–11
bubble, 9, 10f
fork, 10f, 11
origins, 9
prokaryotic DNA, 11
response element sequences, 40
restriction enzymes (REs), 100–4
retinoblastoma, 61, 62–3
retrogenes, 23
retrotransposition, 27
reverse gyrase, 12
reverse transcription PCR, 113
rheumatoid arthritis, 97
ribosomal RNA (rRNA) genes, 24
riboswitch genes, 24
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INDEX
riboswitch RNA, 44
RNA capping, 34
RNA polyadenylation, 34
RNA polymerases, 33
RNA splicing, 35, 45
RNA splicing mutations, 52
RNA-binding proteins, 45
RNA-coding genes, 23, 24
Robertsonian translocation, 52–3
S
S (synthesis) phase, 66
satellite DNA, 25
serum response factor, 40
severe combined immune deficiency (SCID), 95
short interspersed nuclear elements (SINEs), 26
sickle cell anemia, 100f, 101, 106f, 107
signal transducers, 60t
signal transduction pathways, 73–6
mitogen-activated protein kinase, 74f
phosphatidylinositol 3-kinase/PTEN/AKT, 76f
transforming growth factor, 75f
silencer sequences, 39
silent (synonymous) mutations, 49–50
simple sequence repeat (SSR) polymorphism, 57
single nucleotide polymorphisms, 49
site-specific recombination, 19
small interfering (siRNA) genes, 24, 44
small nuclear (snRNA) genes, 24
small nucleolar (snoRNA) genes, 24
somatic cell gene therapy, 133
Sotos syndrome, 129
Southern blotting, 106f, 107
spacer DNA, 49
Splotch (Sp) mutant, 132
sporadic cancers, 71
standard theory of cancer, 71
stat-1, 40
stem cells, 72
adult, 83
embryonic, 83
hemopoietic, 83
steroid hormone receptor, 40
subbands, 7
subregions, 7
sub-subbands, 7
sugars, 1
supercoiling, 11
synapsis, 17
systemic autoimmune disorders, 97
systemic lupus erythematosus (SLE), 37–8
T
T
C arm, 37
T banding, 6
T cells, 83
T lymphocytes, 94–5
endogenous antigens, 83
exogenous antigens, 83
hemopoietic stem cells, 83
immature T cells, 83
mature T cells, 83
negative selection, 83
positive selection, 83
T-cell receptor diversity, 94–5
T-cell receptor structure, 94
telomere, 12
telophase, 68
topoisomerases, 11–2
Towne-Brocks syndrome, 131
TP53 gene, 61–2
trans-acting proteins, 40
transcript mapping, 130
transcription, 33–4
transcription factors, 40, 60t
transfer RNA (tRNA) genes, 37
transitions, 49
translation, 35–7
translocation mutations, 52–3, 58–9
transposons, 26–8
conservative transposition, 27
DNA, 26
genetic variability and, 27–8
long interspersed nuclear elements, 26
long terminal repeat, 26
mechanisms of, 26–7
mutations, 52
retrotransposition, 27
short interspersed nuclear elements, 26
transversions, 49
Treacher-Collins Franceschetti syndrome, 130
trp operon, 47–8
truncated genes, 23
tryptophan, 47–8
tumor necrosis factor, 88t
tumor-suppressor genes, 60–2
caretaker, 61, 62t
gatekeeper, 60, 62t
RB1, 61
TP53, 61–2
22q11.12 deletion syndrome, 95–6
U
unequal crossover, 56
unequal sister chromatid exchange (UESCE), 57
unprocessed pseudogenes, 23
upstream sequences, 33
uracil, deamination of cytosine to, 13
V
variable number tandem repeat (VNTR) polymorphisms, 56–7
large-scale, 57
replication slippage in, 57
simple, 57
unequal crossover in, 56
unequal sister chromatid exchange in, 57
viral vectors, 134–5
adeno-associated, 135
adenoviral, 135
herpes simplex, 135
lentivirus, 135
oncoretroviral, 134
von Recklinghausen disease, 63–4
W
Waardenburg syndrome type 1, 131–2
Warthin-Lynch syndrome, 14–5
Western blot, 120f, 121, 122f, 123
X
X chromosome inactivation, 45
xeroderma pigmentosum, 14
x-linked infantile agammaglobulinemia (XLA), 95, 126f, 127
Y
yeast artificial chromosomes (YACs), 109
Z
zinc finger proteins, 43
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