The Human Genome and Karyotype Flashcards
(133 cards)
1
Q
The amount of DNA in one copy of the genome
A
Genome size (C-value)
2
Q
How many base pairs of DNA do humans have in each somatic cell of our bodies?
A
3.2x10^9 bp
3
Q
How many genes do humans have?
A
Approximately 22,000
4
Q
During mitosis, DNA is packaged into chromosomes. What is the chromosomal make-up of humans?
A
22 pairs of autosomal chromosomes and 2 pairs of sex chromosomes
5
Q
Contain distinct DNA (containing 37 known genes) not
associated with chromosomes. It is inherited solely from the mother in humans
A
Mitochondria
6
Q
Chromatin condenses into chromosomes during
A
Prophase of mitosis (after replication)
7
Q
After DNA is replicated, chromosomes form a pair of sister chromatids attached by the
A
Centromere
8
Q
A higher order of DNA organization where DNA is condensed at least by 10,000 times onto itself
-condensed chromatin fibers
A
Chromosomes
9
Q
Long and thin uncoiled structures found in the nucleus
A
Chromatin
10
Q
Compact, thick, and ribbon-like. These are coiled structures seen prominently during cell division
A
Chromosomes
11
Q
Chromosomes are paired, but chromatin is
A
Unpaired
12
Q
Permissive to DNA replication, RNA synthesis and recombination events
A
Chromatin
13
Q
Not permissive to DNA replication, RNA synthesis and recombination events
A
Chromosomes
14
Q
Generally increases with an organisms complexity
A
Genome size
15
Q
Wide variations exist between genome size and organism complexity; e.g., some single-celled protists have genomes much larger than that of humans. This is called the
A
C-value enigma
16
Q
Does not correlate with genome size or complexity
A
Chromosome number (ploidy)
17
Q
Increased genome complexity/size arises by what two basic mechanisms?
A
Duplication and Incorporation (from other species)
18
Q
In humans, which is more abundant, RNA or DNA?
A
RNA
19
Q
More complex and diverse in its function and may have preceded DNA in evolution
A
RNA
20
Q
Has more chemical stability and thus provides evolutionary advantages
A
DNA
21
Q
Mapped the genome in 80 different human cell types for transcripts and protein-encoding exons, chromatin modification and DNA methylation, DNAse hypersensitivity, and binding of transcription factors
A
Encyclopedia of DNA elements (ENCODE)
22
Q
Identifies cis-regulatory regions where the binding of regulatory factors exposed DNA to cleavage while DNA in nucleosomes is protected
A
DNAse hypersensitivity
23
Q
The ENCODE project concluded that chromatin exists in
A
7 major functional states
24
Q
The ENCODE project concluded that what percentage of chromatin is transcribed into RNA?
A
60-75%
25
The ENCODE project concluded that non-coding transcripts, many predicted to have regulatory roles, are nearly as abundant as
Protein-encoding genes
26
The ENCODE project concluded that there are only 21,000 protein coding genes, but at least 70,000 promoters and how many enhancers?
400,000 enhancers
27
Concluded that At least 80% of the genome is likely to be “functional” implying thatʻnon-coding regionsʼ may be as, or more important than, protein-encoding regions (as determinants of health and disease)
ENCODE
28
Repetitive sequences are common in the human genome and consist of
1. ) Tandem repeats
2. ) Short repeats
3. ) Retrotransposons
29
Repeats which are products of reverse transcription
Retrotransposons
30
Ancient tandem repeats have diverged in nucleotide sequence over time. However, recent repeats (segmental duplications) have a sequence identity of
>90%
31
Create "hot spots" for recombination, increasing the chance of structural change in chromosomes and the frequency of some genetic conditions
Repeats
32
Substrates for recombination because they are similar or identical in nucleotide sequence
Repeats
33
If sequence identity exists in more than 2 places, then what can occur between these regions?
Recombination
34
Depending on the position and orientation of the repeats, recombination between repeats may cause
Inversion, duplication, or deletion
35
Caused by recombination between duplicated genes with almost identical sequence identity on the X-chromosome
Red-green color blindness
36
In red-green colorblindness, there is a misalignment in meiosis followed by
Recombination
37
Due to the presence of three different photoreceptors in the retina, each sensitive to different wavelengths
Color Vision
38
The long (red) and medium (green) wavelength photoreceptors are encoded by genes close together on the
-The two genes differ by only a few bp
X chromosome
39
Recombination during meiosis can delete one gene from the chromosome. Males who carry a deleted X have only one receptor and thus can not distinguish
Long and medium wavelength light
40
Recombination occurs between large repeats resulting in the deletion of a block of DNA that contains multiple genes
-Ex: DiGeorge (Velocardiofacial) Syndrome and Prader-Willi and Angleman syndromes
Contiguous gene (microdeletion or segmental autoploidy) syndromes
41
Characterized by the failure of the pharyngeal pouches to develop. Results in parathyroid, thymus, and cardiac defects
DiGeorge (Velocardiofacial) Syndrome
42
Tandem repeats of sequences of a few hundred base pairs long; hundreds to thousands of copies, mostly at centromeres and telomeres.
Satellite sequences
43
Repeats of a few nucleotides, such as (CA)n dinucleotides. Common, copy number n highly variable. Widely used to identify specific chromosomes in genetic counseling, because often each of the four parental copies will be different.
Micro-Satellites
44
Satellites are called satellites because when DNA is fractionated, there is a small peak next to the DNA peak because it differs in
Base composition
45
Estimated to account for up to 25% of the increased complexity of the human genome
Retrotransposons
46
What are the main types of retrotransposons?
1. ) LINE
2. ) SINE
3. ) Pseudogenes
47
mRNA's encoding reverse transcriptase
LINE (long interspersed nuclear elements)
48
Copies of a short cellular RNA
-Most abundant are Alu sequences
SINE (short interspersed nuclear elements)
49
The most abundant SINEs are Alu sequences, which are unique to human DNA and are named because they contain a restriction site for
Alul
50
Copies of cellular mRNAs
-not transcribed because they lack promoter sequences
Pseudogenes
51
Insertion of reverse-transcribed RNA into DNA can disrupt a gene at an
-An uncommon but well-known cause of genetic disease
Integration site
52
Analysis of the number and structure of chromosomes
Cytogenesis
53
About what percentage of people have an abnormality of chromosome number or structure?
1.5%
54
If there are problems with physical or mental development, infertility, spontaneous abortion, stillbirth, pregnancy in a woman 35 or older, or cancer, you should consider a diagnosis of
Chromosome abnormality
55
Techniques used for visual identification of chromosomes and to detect changes in their structure
Karyotyping
56
What are three karyotyping techniques?
1. ) G banding
2. ) Fluorescent in situ hybridization (FISH)
3. ) Comparative genomic hybridization (CGH)
57
Giemsa staining creates a pattern of dark and light bands unique to each chromosome in
G banding
58
Detects changes in chromosome structure that are too small to see by G banding
-The location must be known in order to design the probe
FISH
59
Detects deletions or duplications even if their location is not known
Comparative Genomic Hybridization (CGH)
60
In G banding, cells are incubated with colchicine, which binds tubulin, prevents spindle function, and
Arrests cells in metaphase
61
Condense steadily during prolonged metaphase.
-With time, the number of cells in mitosis increases but the number of visible bands decreases
Chromosomes
62
The standard karyotype will have how many bands per haploid set of chromosomes?
500-800
63
In G banding, chromosomes are identified by
1. ) Size (1 largest, 22 smallest)
2. ) Centromere position
3. ) Banding pattern
64
A chromosome is made up of what three regions?
1. ) P (short) arm
2. ) Centromere
3. ) Q (long) arm
65
What are three different styles of chromosome?
1. ) Metacentric
2. ) Submetacentric
3. ) Acrocentric
66
The centromere is located in the middle of a
ex: chromosome 3
Metacentric chromosome
67
The centromere is located above the midline, but not at the top of the chromosome in a
-Ex: chromosome 18
Sub-metacentric Chromosome
68
The centromere is located high, towards the top of the chromosome in a
-Ex: chromosome 22
Acrocentric Chromosome
69
Has the centromere at the end of the chromosome
-Not present in humans
Telocentric Chromosome
70
Chromosome bands are numbered on each arm outward from the
Centromere
71
The chromosome bands are further divided with increasing
Resolution
72
Can detect structural changes regardless of the nature or location, but detects only relatively large changes in chromosome structure
G-banding
73
The lower resolution limit of G banding is
One band
74
For metaphase G banding, there are about
500-800 bands
75
A single band is about
4-7 Mb (45 or so genes)
76
To detect smaller changes in a chromosome, we want to use
FISH or CGH
77
Chromatin or chromosomes are fixed to a slide and a fluorescent probe binds to DNA of the complimentary sequence
Fluorescent in situ hybridization (FISH)
78
Faster because it can be done directly on clinical samples
Interphase FISH (on Chromatin)
79
Requires culture to amplify cell number and then incubation in colchicine
Metaphase FISH (on Chromosomes)
80
Has a lower resolution because DNA is not condensed
Interphase FISH
81
Because it is faster, Interphase fish is often used for
Prenatal diagnosis
82
Interphase fish is also used to identify common
Trisomies
83
An example of a use of Metaphase FISH is screening for
DiGeorge syndrome
84
FISH only indicates that a region of DNA complementary to the probe is present. But it will not reveal a single nucleotide deletion/change in the gene or changes elsewhere in the genome. Thus FISH can not rule out a
Mutation or Small deletion in the gene
85
When using FISH, a small deletion will only be revealed with a very specific
Probe
86
Detects alterations too small to be seen by G banding but requires a specific probe and only detects the presence/absence/position of the DNA to which the probe binds
FISH
87
One problem with FISH is that single probes detect the presence of an exon or gene but cannot detect
Single nucleotide changes
88
In FISH, a family of probes can detect a single chromosome or region, but resolution decreases as the number of probes
Increases
89
An array of oligonucleotides are immobilized at different positions on a glass slide (microarray), complementary to sequences spaced across the genome in
Comparative Genome Hybridization (CGH)
90
Compares PCR-amplified patient genome (test) DNA with reference genome (control) DNA in the ability to hybridize with oligonucleotides
CGH
91
You can analyze the CGH by comparing the
Green (patients DNA) to Red (control DNA) ratios
92
For example, if the control has two DNA sequences that hybridize to oligonucleotides, but the patient (Green) experiences a deletion in one of those sequences, the green to red ratio will be
1 : 2, or 0.5 : 1
93
Detects very small changes anywhere in the genome
-i.e. you do not need to know where to look
CGH
94
A weakness of CGH is that it detects only
Deletions or duplications
95
CGH can not detect rearrangements without gain or loss, such as
Inversions or translocations
96
Refers to the chromosome number
Ploidy
97
Sperm have one copy of each chromosome, meaning they are
Haploid (N)
98
Zygotes and somatic cells contain two copies of each chromosome, meaning they are
Diploid (2N)
99
In diploid cells, the two copies of each chromosome are
Homologues (form a homologous pair)
100
Normally, one homologue is maternal, from the egg, and one is paternal, from the sperm. They carry the same genes in the same order, but not necessarily identical
Alleles
101
If the homologous chromosomes differ genetically, normally they are distributed into gametes in a 1:1 ratio. This is what gives rise to
Mendel's Laws
102
Diploid conceptions with two maternal or two paternal chromosomes are not
Viable
103
Characterized as having a normal number of chromosomes: 22 pairs of autosomes and one pair of sex chromosomes
Euploidy
104
The karyotype designation for Euploidy is
46, XX or 46, XY
105
Characterized as having missing (2N-1, monosomy) or extra (2N+1, trisomy) chromosomes
Aneuploidy
106
Aneuploidy for most chromosomes is
-exceptions: X, Y and trisomy for a few small autosomes
Lethal
107
When 2 sperm fertilize one egg resulting in 3 complete chromosome sets
-Lethal
Triploidy
108
Down syndrome in a male is indicated by
Trisomy 21
Karyotype designation: 47, XY, +21
109
Down syndrome in a female is indicated by
Trisomy 13
Karyotype designation: 47, XX, +13
110
A female with monosomy X (45, X) has
-only nonlethal monosomy
Turner's syndrome
111
When genetic material is moved from one chromosome to another
Translocation
112
What are the two types of translocation?
1. ) Reciprocal
| 2. ) Non-reciprocal
113
When 2 chromosomes exchange segments
Reciprocal translocation
114
The movement of DNA from one chromosome to another
Non-reciprocal Translocation
115
When a segment of DNA is inverted with respect to the rest of the chromosome
Inversion
116
What are three abnormalities in chromosome structure
1. ) Translocation
2. ) Inversion
3. ) Duplication or deletion
117
When a double stranded DNA break occurs, the chromosomes are healed by recombination, NHEJ, or slower backup mechanisms. If the ends are not rejoined correctly, there will be a
Structural alteration of the chromosome
118
Structural alterations of a chromosome are important in carcinogenesis because they can alter gene structure or expression. They are increased by
Radiation
119
The general rule is that the number of chromosomes = the
Number of centromeres
120
The identity of a chromosome = the identity of its
Centromere
121
Most common translocations are between
Acrocentric autosomes
122
Breakpoints occur within the centromeres of D- and G-group chromosomes, with fusion of chromosomes and loss of p arms
-i.e. two q arms fuse together and lose their p arms
Robertsonian Translocations
123
Is Robertsonian translocation always lethal?
No, not always
124
During metaphase, the Robertsonian chromosome will pair with
2 chromosomes (1 that contains one q arms and the other containing the other q arm)
125
In Robertsonian translocation, the pairing of homologous chromosomes during metaphase will occur between
3 chromosomes (2 normal and 1 translocation)
126
A chromosome where both arms are from the q arm of chromosome 21
Isochromosome 21 (i21q)
127
Fertilization of a cell with i21q will result in either
trisomy 21 (downs) or monosomy 21 (lethal)
128
Any live-born children with i21q qill have
Down Syndrome
129
An inversion in which the break points are in different arms of the same chromosome and thus the inversion includes the centromere
Pericentric inverison
130
Inversion where the 2 breakpoints are in the same arm and thus the centromere is not included in the inversion
Paracentric inversion
131
What does 46, XY, t(1:3)(q31;q24) mean?
Male with 46 chromosomes that has a translocation between chromosomes 1 and 3, and the position of the translocation is the q31 for chromosome 1 and q24 for chromosome 3
132
What does rob(14;21) mean?
Robertsonian translocation where the q arms of chromosomes 14 and 21 are joined
133
What does 46, XY, inv(6)(p23;q21) mean
A male with 46 chromosomes has an inversion on chromosome 6 between p23 and q21, and since the inversion is in different arms, it is a pericentric inversion
