Lesson 6 - Genetic Basis Of Human Diseases Flashcards
1
Q
A scientific discipline that bridges the gap between classical genetics and the microscopic world of chromosomes
A
Cytogenetics
2
Q
By studying the structure and number of chromosomes in an individual’s cells, cytogenetics helps us understand the link between ____ and various ____.
A
Chromosomal abnormalities; genetic conditions
3
Q
(3) Cytogenetic Techniques
A
Karyotyping
FISH (Fluorescence in situ Hybirdization)
CGH (Comparative Genetic Hybridization)
4
Q
What cytogenetic technique?
Analyzing the number and structure of chromosomes
A
Karyotyping
5
Q
What cytogenetic technique?
targeting specific DNA sequences
A
FISH (Fluorescence in situ Hybridization)
6
Q
What cytogenetic technique?
detecting chromosomal gains or losses
A
CGH (Comparative Genomic Hybridization)
7
Q
Cells are cultured and then artificially arrested in mitosis during ____ (or ____)
A
Metaphase; prometaphase
8
Q
The most commonly used banding and staining method is the ____ (___)
A
GTG Banding; G-bands trypsin Giemsa
9
Q
GTG banding is also known as
A
G Banding
10
Q
XX meaning
A
Female
11
Q
XY meaning
A
Male
12
Q
[##] meaning
A
Number [#] of cells
13
Q
cen meaning
A
Centromere
14
Q
del meaning
A
Deletion
15
Q
der meaning
A
Derivative
16
Q
dup meaning
A
Duplication
17
Q
ins meaning
A
Insertion
18
Q
inv meaning
A
Inversion
19
Q
ish meaning
A
Metaphase FISH
20
Q
nuc ish meaning
A
Interphase FISH
21
Q
mar meaning
A
Marker
22
Q
mos meaning
A
Mosaic
23
Q
p meaning
A
Short arm
24
Q
q meaning
A
Long arm
25
r meaning
Ring chromosome
26
t meaning
Translocation
27
ter meaning
Terminal
28
/ meaning
Slash
29
+ meaning
Gain of
30
— meaning
Loss of
31
Normal female Karyotype
46, XX
32
Normal male karyotype
46, XY
33
Number of cells in each clone, typically inside brackets Mosaicism in Klinefelter syndrome with 12 normal cells and 10 cells with an extra X chromosome
46, XY[12]/47, XXY[10]
34
Male with deletion of chromosome 5 short arm
46, XY, del(5p)
35
Female with structurally rearranged chromosome 2 that resulted from a translocation between chromosomes 2 (short arm) and 7 (long arm)
46, XX, der(2), t(2p12;7q13)
36
Male with interstitial duplication in the long arm of chromosome 15 in the Prader-Willi/Angelman syndrome region
46, XY, dup(15)(q11-q13)
37
Male with an insertion within chromosome 3
A piece between q21q26 has reinserted on p13
46, XY, ins(3)(p13q21q26)
38
Male with pericentric inversion of chromosome 2 with breakpoints at bands p21 and q31
46, XY, inv(2)(p21q31)
39
Female with deletion in the Williams syndrome region detected by in situ hybridization
46, XX.ish del(7)(q11.23q11.23)
40
Interphase in situ hybridization showing 3 signals for the X centromeric region
nuc ish(DXZ1 x 3)
41
Male with extra, unidentified chromosome material
47, XY, +mar
42
Turner syndrome mosaicism (analysis of 30 cells showed that 14 cells were 45,X and 16 cells were 46,XX)
mos 45,X[14]/46, XX[16]
43
Male with deletion on the short arm of chromosome 5, band p12 (short nomenclature)
46,XY, del(5)(p12)
44
Male with a deletion on the long arm of chromosome 5, band 14
46, XY, del(5)(p14)
45
Female with 1 normal X chromosome and a ring X chromosome
46, X, r(X)(p21q27)
46
Interchange of material between chromosome 2 and 8 with breakpoints at bands 2q33 and 8q24.1
t(2;8)(q33;q24.1)
47
Male with a deletion of chromosome 5 between p12 and the end of the short arm (long nomenclature)
46, XY, del(5)(p12-pter)
48
Separate lines or clones
Mosaicism for monosomy X and a male cell line
45, X / 46, XY
49
Female with trisomy 21
47, XX, +21
50
Male with monosomy 21
45, XY, -21
51
identifying chromosomal abnormalities in fetuses
Prenatal Diagnosis
52
(3) Clinical applications of cytogenetics
Prenatal diagnosis
Cancer diagnosis
Genetic counseling
53
detecting chromosomal rearrangements in tumors
Cancer diagnosis
54
informing couples about the risk of passing chromosomal disorders
Genetic counseling
55
Far more common that is widely appreciated
Genetic disorders
56
Genetic disorders
Lifetime frequence is estimated to be ____ per ____
670;1000
57
Less extreme genotypic errors permit _____ and ____
Full embroyonic development; live birth
58
Estimated that ___% of spontaneous abortuses early in gestation demonstrate chromosomal abnormality
50
59
About ___% of all newborn infants possess a gross chromosomal abnormality
1
60
Serious disease with a significant genetic component develops in approximately __% of individuals younger than age ___ years
5; 25
61
Cause the disease or predispose to disease
Disorders related to mutations in single genes with large effects
62
Highly penetrant
Disorders related to mutations in single genes with large effects
63
Caused by single gene mutations and usually follow the classic Mendelian pattern of inheritance
Disorders related to mutations in single genes with large effects
64
Generally rare unless maintained in a population by strong selective forces
Disorders related to mutations in single genes with large effects
65
Chromosomal disorders arise from ____ or ___ in the autonomies and sex chromosomes
Structural; numerical alteration
66
Chromosomal disorders are ___ but associated with ___
Uncommon; high penetrance
67
Caused by interactions between multiple variant forms of genes and environmental factors
Complex multigenic disorders
68
Complex multigenic disorders are far more ___
Common
69
Variant gene confers small increase in disease risk, no susceptible gene is necessary to produce the disease
Polymorphisms
70
This is under polymorphisms
Complex multigenic disorders
71
Complex multigenic disorders occurs when several polymorphisms occur that in ____ or _____
Multigenic or polygenic diseases
72
Small effect and has low penetrance
Complex multigenic disorders
73
Environmental interactions are important in pathogenesis ~ multifactorial disorders (4)
Hypertension
Atherosclerosis
Diabetes mellitus
Autoimmune diseases
74
A permanent change in DNA
Mutations
75
Germ cells = ___
Inherited diseases
76
Somatic cells = ____
Cancers and some congenital malformations
77
Point mutations within coding sequences (3)
Silent mutations
Missense mutations
Nonsense mutations
78
Frameshift mutations (2)
Deletion
Insertion
79
(4) mutations
Point mutations within coding sequences
Mutations within noncoding sequences
Deletions and Insertions (Frameshift mutations)
Trinucleotide-repeat mutations
80
Genetic mutation where a single nucleotide base is changed, inserted or deleted from a sequence
Point mutation
81
Mutations in DNA that do not have an observable effect on the organism's phenotype
Silent mutation
82
Silent mutations are a specific type of _____
Neutral mutation
83
Mutations that alter the meaning of the sequence of the encoded protein
Missense mutation
84
Type of missense mutation (2)
Conservative
Nonconservative
85
Type of missense mutation
Substituted amino acid is biochemically similar to the original and causes little change in function
Conservative
86
Type of missense mutation
Replaces the normal amino acid with a biochemically different one
Nonconservative
87
A point mutation may change amino acid codon to a chain terminator or stop codon
Nonsense mutation
88
Signals the cell to stop building protein which results in a shortened protein that may function improperly or not at all
Nonsense mutation
89
Interfere with binding of transcription factors and leads to marked reduction or lack of transcription
Mutations with noncoding sequences
90
Interfere with binding of transcription factors and leads to marked reduction or lack of transcription such as ____
Thalassemias
91
Mutations with noncoding sequences may lead to ___ of intervening sequences and results to form a mature ____ . Therefore translation cannot take place and the gene product is not ____.
Defective splicing; mRNA
Synthesized
92
involves the loss of one or more nucleotides (in multiple of threes of not) from a segment of DNA
Deletion
93
Permanent change in DNA sequence caused by the addition of nucleotides (in multiple of three or not)
Insertion mutation
94
Small deletions or insertions of base pairs involved is three or multiple of three
Non-frameshift mutation
95
The reading frame of non-frameshift mutation will remain ___ and an abnormal protein lacking or gaining one or more amino acids will be ____
Intact; synthesize
96
The number of affected coding bases is not a multiple of threes
Frameshift mutations
97
The frameshift mutation results in an altered reading frame if the DNA strand typically results in incorporation of a ___ number of incorrect amino acids followed by a premature ____ codon
Variable; stop
98
The frameshift mutation results in an altered reading frame if the DNA strand typically results in incorporation of a ___ number of incorrect amino acids followed by a premature ____ codon
Variable; stop
99
Characterized by amplification of a sequence of three nucleotides
Trinucleotide-Repeat mutations
100
Specific nucleotide sequence that undergoes amplication differs in various disorders, almost all affected sequences share the nucleotides ____ and ___
Guanine (G); cytosine (C)
101
These disorders are caused by expansion in the number of 3-bp repeats
Triple repeat expansion disorders
102
Triplet repeat expansion disorders include (4)
fragile X syndrome
myotonic dystrophy
Huntington disease
spinocerebellar ataxias
103
Triple repeat expansion disorder can result to loss of protein production when gene becomes ____
Hypermethylated
104
Triple Repeat Expansion Disorders
Some can cause disease through a mechanism other than decreased protein production like in Huntington disease, expansion causes the gene product to have a _____ effects on the ____
Toxic; neurons
105
For most triplet repeat disorders, there is a clinical correlation to the size of the expansion, with a greater expansion causing more severe symptoms and having an earlier age of disease onset
Anticipation
106
Thread-like structures found within the nucleus of a cell
Chromosome
107
Chromosome contains the ___ material
Hereditary
108
Humans have ___ chromosomes organized into ___ pairs
46; 23
109
Chromosome is an organized structure where the DNA is tightly packed with histones forming the ____
Chromatin
110
Each chromosome is made up of identical copies, called ____, held together by _____.
Sister chromatids; centromere
111
Tips of the chromosome are guarded by ____, which prevent from ____
Telomeres; fraying
112
Chromosomes are the foundation of ____, holding the information of our ____ and shaping the _____we inherit
Heredity
Ancestry; traits
113
The chromosome’s complex structure allows for the precise ____ and transmission of _____
Replication; genetic information
114
Chromosomal disorders variation (5)
Variation in chromosome number
Variation in chromosome size
Variation in the arrangement of chromosome segments
Variation in the number of chromosome segments
Variation in chromosome morphology
115
Any exact multiple of the haploid number of chromosomes (23)
Euploid
116
Type of polyploidy (1)
Triploidy
117
Types of aneuploidy
Monosomy
Trisomy
118
Euploid cells with more than the normal diploid number of 46 (2n) chromosomes: 3n, 4n
Euploid
119
Those with 3 haploid sets of chromosomes (3n)
Triploidy
120
An error occurs in meiosis or mitosis and a cell acquires a chromosome complement that is not the exact multiple of 23
Aneuploidy
121
Occur when only 1, instead of the normal 2, of a given chromosome is present
Monosomy
122
In humans, most autosomal monosomies appear to be ____ early in development, and survival is possible in mosaic forms except in ____
Lethal
Turner syndrome (45,X)
123
Results from complete or partial monosomy of the X chromosome
Turner Syndrome 45,X
124
Turner syndrome characterized primarily by ____ in phenotypic females
Hypogonadism
125
the failure of chromosomes to disjoin normally during meiosis
Nondisjunction
126
Characterized by the presence of 3 chromosomes, instead of the normal 2, of any particular chromosome
Trisomy
127
Monosomy is the most common sex chromosome abnormality in ____, affecting about ___ in ____ live-born females
Females
1; 2500
128
Most common form of aneuploidy
Trisomy
129
Trisomy 21
Down syndrome
130
Trisomy 18
Edwards syndrome
131
Trisomy 13
Patau syndrome
132
47, XXY
Klinefelter syndrome
133
Most common of the chromosomal disorders and is a major cause of mental retardation
Down Syndrome or Trisomy 21
134
Approximately 1% of Down syndrome patients are ____
Mosaics
135
Male hypogonadism that occurs when there are two or more X chromosomes and one or more Y chromosomes
Klinefelter syndrome
136
Loss of a portion of a chromosome
Deletions
137
Most are ____ but rarely terminal deletions may occur
Interstitial
138
Formation of a ring chromosome by a break in each arm, loss of the terminal segments and union of the centric segment
Ring chromosome
139
The presence of extra genetic material from the same chromosome
Duplication
140
breaks are in the 2 opposite arms of the chromosome and include the centromere
Pericentric inversions
141
Occur when a piece of a chromosome broken at 2 points is incorporated into a break in another part of a chromosome
Insertion
142
Occur when a piece of a chromosome broken at 2 points is incorporated into a break in another part of a chromosome
Insertion
143
Consist of 2 copies of the same chromosome arm joined through a single centromere and forming mirror images of one another
Isochromosome
144
Involve the transfer of material from one chromosome to another
Translocation
145
Result of breaks in nonhomologous chromosomes with reciprocal exchange of the broken segments
Balanced Reciprocal Translocation
146
Translocation between two acrocentric chromosomes
Robertsonian Translocation or Centric Fusion
147
Robertsonian Translocation or Centric Fusion significance also lies in the production of ____
Abnormal progeny
148
refers to traits that are caused by a combination of inherited, environmental, and stochastic factors
Multifactorial inheritance
149
refers to traits that result from the additive effects of multiple genes
Polygenic inheritance
150
Example of Triplenucleotide-Repeat Disorder (7)
Dentatorubral-pallidoluysian atrophy
Fragile-X syndrome
Friedreich’s ataxia
Hungtington’s disease
Myotonic dystrophy
Spinobulbar muscular atrophy
Spinocerebellar ataxia
151
Example of trisomy syndrome (3)
Trisomy 13 (Patau syndrome)
Trisomy 18 (Edwards syndrome
Trisomy 8 (mosaicism)
