Week 01 Genomes, Genes, Mutations Flashcards
(86 cards)
1
Q
genome
A
the entire collection of genetic material within an organism
2
Q
chromosome
A
structure consisting of DNA and associated proteins that carries and transmits genetic information
Each unreplicated chromosome consists of a single molecule of DNA.
3
Q
Compare the chromosomes of prokaryotes vs eukaryotes with respect to:
- number
- shape
- location
- extra dna
- accompanying proteins
- replication
- percentage expressed
- repeats
A
-
number:
- prokaryotes: 1
- eukaryotes: >1
-
shape:
- prokaryotes: circular
- eukaryotes: linear
-
location:
- prokaryotes: cytoplasm
- eukaryotes: nucleus
-
extra dna:
- prokaryotes: plasmids
- eukaryotes: in organelles (e.g. mitochondria, chloroplasts)
-
accompanying proteins:
- prokaryotes: no, ‘naked’
- eukaryotes: packaged with histones to form chromatin
-
replication:
- prokaryotes: binary fission
- eukaryotes: mitosis and meiosis
-
percentage expressed:
- prokaryotes: >90% expressed
- eukaryotes: <10% expressed
-
repeats:
- prokaryotes: very few repeats
- eukaryotes: many repeats
4
Q
ploidy
A
the number of sets of homologous chromosomes in the genome of a cell or an organism (e.g. monoploid, diploid, triploid, polyploid)
5
Q
haploid number
A
The haploid number (n) refers to the total number of chromosomes found in a gamete (a sperm or egg cell produced by meiosis in preparation for sexual reproduction).
Depending upon the polidy of the organism, the chromosome number in somatic cells will be some multiple of this e.g. diploid = 2n, triploid = 3n
6
Q
total chromosome number
A
Depending upon the ploidy of the organism, the chromosome number in somatic cells will be some multiple of the haploid number e.g. diploid = 2n, triploid = 3n.
Most animals are diploid, so e.g. humans have 2n where n = 23 so 2n = 46 chromosomes
7
Q
euploidy
A
The state of a cell or organism having or ganing one or more than one set of the same set of chromosomes, possibly excluding the sex-determining chromosomes.
For example, most human cells have 2 of each of the 23 homologous monoploid chromosomes, for a total of 46 chromosomes.
A human cell with one extra set of the 23 normal chromosomes (functionally triploid) would be considered a case of abberant euploidy. This would also result in polyploidy, the organism’s having >2 sets.
8
Q
aneuploidy
A
Aneuploidy is the state where one or more individual chromosomes of a normal set are absent or present in more than their usual number of copies (excluding the absence or presence of complete sets, which is considered euploidy).
Unlike euploidy, aneuploid karyotypes will not be a multiple of the haploid number.
Examples: Down syndrome = extra copy of chromosome 21; Turner syndrome = partly or missing X chromosome
Veterinary example: XXY trisomy in male tortoiseshell cats (Klinefelter syndrome)
9
Q
karyotype
A
The complete set of chromosomes possessed by an organism
usually presented as a picture of a complete set of its metaphase chromosomes
Can be used to identify chromosomal abnormalities
10
Q
chromatin
A
Material found within the eukaryotic nucleus; consists of DNA and histone proteins
Chromatine regulates gene expression
11
Q
What are the three essential elements of a functioning (eukaryotic) chromosome?
A
- Centromere
- Pair of telomeres
- Origins of replication
12
Q
centromere
A
- appears as a constricted region on the chromosome
- serves as the attachment point for spindle microtubules
- Before cell division, a multiprotein complex called the kinetochore assembles on the centromere; later, spindle microtubules attach to the kinetochore
- Chromosomes lacking a centromere cannot be drawn into the newly formed nuclei; such chromosomes are lost, often with catastrophic consequences for the cell (p. 22)
13
Q
telomere
A
- Telomeres are the specific DNA sequences and associated proteins located at the tips of whole linear chromosomes
- telomeres protect and stabilize the chromosome ends
- telomeres also participate in limiting cell division and may play important roles in aging and cancer
14
Q
origins of replication
A
- sites where DNA synthesis begins;
- unlike centromeres and telomeres, they are not easily observed by microscopy
15
Q
nucleosome
A
- the basic structural unit of DNA packaging in eukaryotes, comprised of a section of DNA that is wrapped around a core of (histone) proteins
- Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight histone proteins, which are known as a histone octamer
16
Q
What is the difference between the relaxed and supercoiled states of chromatin?
A
Relaxed (extended)
- Required for gene expression
- Most of cell cycle
- Not visible under microscope
Supercoiled (condensed)
- NO gene expression
- During mitosis and meiosis
- Visible under microscope
17
Q
euchromatin
A
- a lightly packed form of chromatin that is enriched in genes
- is often (but not always) under active transcription
- Euchromatin comprises the most active portion of the genome within the cell nucleus
- ‘beads on a string’
18
Q
heterochromatin
A
Heterochromatin
- Generally condensed (not just meiosis)
- Minimal gene expression
- Few recombination events
- Constitutive or Facultative
19
Q
Constitutive heterochromatin
A
- ALWAYS condensed
- Centromeres, telomeres, repeat sequences (high numbers of tandem repeats)
20
Q
tandem repeats
A
Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other
21
Q
Facultative heterochromatin
A
- SOMETIMES condensed
- Not repeat sequences
- Example: X chromosome inactivation in female mammals: one X chromosome is packaged as facultative heterochromatin and silenced, while the other X chromosome is packaged as euchromatin and expressed
22
Q
In a karyotype image, we typically visualize chromosomes in their [relaxed/supercoiled], [replicated/unreplicated] form during meiosis/mitosis
A
In a karyotype image, we typically visualize chromosomes in their supercoiled, replicated form during meiosis/mitosis
23
Q
On the basis of the location of the centromere,
chromosomes are classified into four types. What are the names of these four types?
A
- Metacentric
- Submetacentric
- Acrocentric
- Telocentric
24
Q
Where is the location of the centromere in a metacentric chromosome (during metaphase)?
A
Centromere is in the middle such that the two arms of the chromosome are almost equal in length
25
Where is the location of the centromere in a *submetacentric* chromosome (during metaphase)?
Centromere is not in the middle, such that the dwo arms of the chromosomes are unequal. When unreplicated they form an L shape.
26
Where is the location of the centromere in an *acrocentric* chromosome (during metaphase)?
If the p (short) arm is so short that it is hard to observe, but still present, then the chromosome is acrocentric.
From Latin *acro-* "sharp, tip, peak, extremity" from Ancient Greek *ákros* "highest, at the extremity"
27
Where is the location of the centromere in an *telocentric* chromosome (during metaphase)?
A telocentric chromosome's centromere is located at the terminal end of the chromosome. A telocentric chromosome has therefore only one arm.
28
What is the example of chromosome staining in animals discussed in the lectures called? What are the two types of bands that can be visualised and what does this stain tell us?
Giemsa stain in animals
* G bright bands = gene-rich, GC rich, fewer repeats
* G dark bands = gene-poor, AT rich, more repeats
29
One way to view chromosomes microscopically is to stimulate them to divide mitotically then treat them with . This prevents formation of the apparatus, causing the accumulation of chromosomes in the stage of mitosis. In this form the are clearly visible under the microscope.
One way to view chromosomes microscopically is to stimulate them to divide mitotically then treat them with **_colichine_**. This prevents formation of the **_spindle_** apparatus, causing the accumulation of chromosomes in the **_metaphase_** stage of mitosis. In this form the are clearly visible under the microscope.
30
What are the three parts of the basic structure of a gene and their basic functions?
1. Promoter: Site of RNA Polymerase binding
2. Transcribed region: Transcribed into RNA and can include untranslated regions
3. Terminator: RNA Polymerase releases – transcription ends
31
In prokaryotic genes, the promoter is part of the region of the gene.
In prokaryotic genes, the promoter is part of the **_regulatory_** region of the gene.
32
In prokaryotic genes, the **transcribed** region includes (1) [**_5' untranslated region/3' untranslated region/both_**], (2) the protein coding region, and (3) [**_introns/no introns_**].
In prokaryotic genes, the **transcribed** region includes (1) **_both_** 5' and 3' untranslated regions, (2) the protein coding region, and (3) _**no** introns_.
33
Some genes in bacteria are in **operons** (this not true in eukaryotes). What does this mean?
Several genes are controlled by the same promoter.
34
In eukaryotic genes, both exons and introns exist in the transcribed region. Exons are [**_transcribed and/spliced out and not_**] translated into proteins. Introns are [**_transcribed and/spliced out and not_**] translated into proteins.
In eukaryotic genes, both exons and introns exist in the transcribed region. Exons are **transcribed and** translated into proteins. Introns are **spliced out and not** translated into proteins.
35
Enhancers are found [**_upstream/downstream_**] to the coding regions in a gene (towards the 5' end). Gene regularoty proteins/transcription factors can bind to these regions to up or downregulate transcription of a particular gene.
Enhancers are found **upstream** to the coding regions in a gene (towards the 5' end). Gene regularoty proteins/transcription factors can bind to these regions to up or downregulate transcription of a particular gene.
36
The three main types of transcription factors in eukaryotic genes are:
1. General transcription factors
2. Positive transcription factors (activator proteins)
3. Negative transcription factors (repressors)
37
Over 80% of what used to be called "junk" DNA we now know is translated into RNA. What are some of these types of RNA?
38
What is RNAi?
RNA interference: Extragenic sequences control expression of protein coding genes
39
What are four sites for the control of gene expression?
1. Transcription factors
* Bind promoters and enhancers
* Affect binding of RNA polymerase
* Most genes are affected by several transcription factors
2. Chromatin
* Nucleosome packaging
* Histone modifications (eg: acetylation)
3. DNA modifications
* eg: methylation of CpG nucleotides in gene promoters to suppress gene expression
4. RNAi
* Affects abundance of mRNA
40
Epigenetics
Stable, heritable phenotypes resulting from changes in a chromosome without alterations in the DNA sequence (e.g. Chromatin modifications, DNA modifications, Small RNA)
May or may not be transgenerational (ie can be somatic or germline)
e.g. agouti mice
41
\_\_\_\_\_\_-\_\_\_\_\_\_\_ mutations arise in cells that ultimately produce
gametes.
**Germ-line** mutations arise in cells that ultimately produce
gametes.
42
What is a **base substitution** mutation and what are the two types?
* The alteration of a single nucleotide in the DNA
1. **Transition**: a puring replaced by a different purine, or a pyrimidine replaced by a different pyrimidine
2. **Transversion**: A purine is replaced by a pyrimidine or *vice versa*
43
What is the term for mutations by **insertion or deletion** of one or more nucleotide pairs?
These are the most frequent type of mutation and may lead to a **frameshift mutation**. Define this term.
* Indels
* Change in the reading frame of the gene
* Alter all downstream amino acids so may have large phenotypic effects
* May also produce premature *stop* codons
44
Define "in-frame" insertions/deletions
Indels that do not affect the reading frame of a gene (may, for example, delete three base pairs)
45
What is the term for the phenomenon in which the number of copies of a set of nucleotides increases?
expanding nucleotide repeats
46
Forward mutation
A mutation that alters the wild-type
phenotype
47
Reverse mutation (reversion)
Changes a mutant phenotype back to the wild type
48
Term for a base substitution that results in a different amino acid in the protein?
missense mutation
49
Term for a mutation that changes an amino acid specifying codon into one that terminates translation (a stop codon)?
Nonsense mutation
If a nonsense mutation occurs early in the mRNA sequence, the protein will be truncated and usually nonfunctional
50
Term for a mutation that changes a codon to a synonymous codon that specifies the same amino acid?
Silent mutation
51
What is a **neutral mutation**?
a missense mutation that alters the amino acid sequence of a protein but does not significantly change its function.
52
What is the term for a mutation that causes the complete or partial absence of normal protein functions?
Loss-of-function mutation
e.g. mutations that cause cystic fibrosis: produce a nonfunctional form of the CFTR protein, which normally regulates the movement of chloride ions into and out of the cell
53
What is the term for a mutation that causes the cell to produce a protein or gene product whose function is not normally present?
gain-of-function mutation
The result could be an entirely new gene product or one produced in an inappropriate tissue or at an inappropriate time in development
54
What is the term for mutations that are only expressed under certain conditions (e.g. only at elevated temperatures)?
conditional mutations
55
What is the term for mutations that produce premature death?
Lethal mutations
56
What is a **suppressor mutation**?
genetic change that hides or suppresses the effect of another mutation
A suppressor mutation occurs at a site distinct from the site of the original mutation; thus, an individual with a suppressor mutation is a double mutant, possessing both the original mutation and the suppressor mutation but exhibiting the phenotype of the nonmutated wild type.
57
What are the terms for the two types of **suppressor mutations**?
intragenic
intergenic
58
What is the difference between a somatic and a germline mutation?
59
What is the name for a mutation where a section of a genetic sequence gets flipped around and reversed end-to-end?
inversion
60
What are some causes (internal process and environmental) of small scale mutations?
Errors in natural processes
* DNA replication/synthesis
* DNA repair
* Recombination
Environmental
* Radiation
* Chemicals
* Cause DNA damage produce errors in repair
61
Mutations that are brought about by internal processes during normal conditions are termed **mutations.** Those caused by environmental factors such as exposure to mutagenic chemicals or radiation are termed **mutations**.
Mutations that are brought about by internal processes during normal conditions are termed **spontaneous mutations.** Those caused by environmental factors such as exposure to mutagenic chemicals or radiation are termed **induced mutations**.
62
What are the terms for:
**(a)** the spontaneous replication error that arises through changes in how protons (H ions) are positioned in DNA bases, leading to non-standard base-bairings (e.g. C-A instead of C-G), and
**(b)** the phenomenon that causes conditions in which normal, protonated, and other forms of the bases are able to pair because of flexibility in the DNA helical structure
(a) Tautometric shifts
(b) wobble
63
What are **transposons**/transposable elements?
What is the term that describes their moving about?
* DNA sequences that can move about in the genome (using *transposase* enzyme). Most transposable elements can insert themselves at many different locations in the genome, relying on mechanisms that are distinct from homologous recombination. Often a cause of mutations (Shift DNA segments; Gene disruption).
* **transposition**
64
What is a **chromosome mutation**?
Variations that arise in chromosome *number* (such as extra sets) or *structure* (individual chromosomes may lose or gain parts, and the order of genes within a chromosome may be altered)
65
What are the three basic types of chromosome mutation?
1. Chromosome rearrangements (of parts)
2. Aneuploidy
* the number of chromosomes is altered: one or more individual chromosomes are added or deleted
3. Polyploidy
* one or more complete sets of chromosomes are added
66
What are the four basic types of chromosome rearrangements?
1. duplications
2. deletions
3. inversions
4. translocations
67
With respect ot chromosomal duplication (can be *part* of the chromosome doubled), define:
1. Tandem duplication
2. Displaced duplication
3. Reverse duplication
4. Segmental duplicaitons
1. **Tandem** duplication: the duplicated segment is immediately adjacent to the original segment
2. **Displaced** duplication: the duplicated segment is located some distance from the original segment, either on the same chromosome or on a different one
3. **Reverse** duplication: the duplication is inverted (e.g. ABCD : DCBA)
4. **Segmental** duplicaitons: duplications greater than a thousand base pairs (bp) in length. May be *intrachromosomal* duplications (i.e., the two copies are found on the same chromosome), or *interchromosomal* duplications (the two copies are found on different chromosomes).
68
What is the term for the process by which duplications and deletions may arise from the misalignment of chromosomes during crossing over?
**Unequal crossing over**
This is frequently the cause of red-green color blindness in humans.
69
What is haploinsufficiency?
When a single copy of a gene is not sufficient to produce a wild-type phenotype (two copies are needed)
70
What is a (chromosomal) **translocation**?
A **translocation** entails the movement of genetic material between *nonhomologous* chromosomes or within the same chromosome. Translocation should not be confused with **crossing over**, in which there is an exchange of genetic material between *homologous* chromosomes.
71
What is the term describing when genetic material moves from one chromosome to another (translocation) without any exchange in return?
nonreciprocal translocation
72
What is the term describing when genetic material moves from one chromosome to another (translocation) with an exchange also in return of material from that chromosome to the first?
**reciprocal translocation**
* Errors in chromosome alignment during meiosis (subfertility)
* **Balanced** = complete chromosome complement (Phenotypic effects unlikely; reduced fertility)
* **Unbalanced** = duplication and deletion (Lethal or phenotypic effects likely; segregation problems during meiosis)
73
What are two possible effects of translocations?
* they can physically link genes that were formerly located on different chromosomes
* may affect gene expression (a position effect)
* the chromosome breaks that bring about translocations may take place *within* a gene and disrupt its function
74
What is a **Robertsonian translocation**?
* the long arms of two acrocentric chromosomes become joined to a common centromere through a translocation, generating a metacentric chromosome with two long arms and another chromosome with two very short arms
* The smaller chromosome is often lost because very small chromosomes do not have enough mass to segregate properly during mitosis and meiosis. The result is an overall reduction in chromosome number
75
Chromosome rearrangements and copy-number variations are collectively referred to as **\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_**.
Chromosome rearrangements and copy-number variations are collectively referred to as **structural variants**
76
What are the four common types of aneupolidy in diploid organisms?
1. **Nullisomy**: loss of both members of a homologous pair of chromosomes (*2n - 2*)
2. **Monosomy**: loss of a single chromosome (*2n - 1*)
3. **Trisomy**: gain of a single chromosome (*2n + 1*)
4. **Tetrasomy**: gain of two homologous chromosomes (*2n + 2*)
77
Nondisjunction in a mitotic division may generate patches of cells in which every cell has a chromosome abnormality and other patches in which every cell has a normal karyotype. This type of nondisjunction leads to regions of tissue with different chromosome constitutions, a condition known as **\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_**.
Nondisjunction in a mitotic division may generate patches of cells in which every cell has a chromosome abnormality and other patches in which every cell has a normal karyotype. This type of nondisjunction leads to regions of tissue with different chromosome constitutions, a condition known as **genetic mosaicism**.
78
Polyploidy
possession of more than two sets of chromosomes
79
What are the two types of polyploidy?
**autopolyploidy**, in which all chromosome sets are from a single species, and **allopolyploidy**, in which chromosome sets are from two or more species (e.g. wheat)
80
What is **nondisjunction** and what are the three ways it can arise?
The failure of homologous chromosomes or sister chromatids to separate properly during cell division:
1. failure of a pair of **homologous chromosomes** to separate in **meiosis I**
2. failure of **sister chromatids** to separate during **meiosis II**
3. failure of **sister chromatids** to separate during **mitosis**
81
What are the consequences of nondisjunction during meiosis I for gametes and zygotes?
* homologous pair fails to split
* 100% abnormal gametes
* Zygotes (assuming second parent normal):
* 50% Trisomy
* 50% Monosomy
* Lethal or phenotypic effects likely
82
What are the consequences of nondisjunction during meiosis II for gametes and zygotes?
* set of sister chromatids fail to split
* Gametes
* 50% normal gametes
* 50% abnormal gametes
* Zygotes (assuming second parent normal):
* 50% Normal
* 25% Trisomy
* 25% Monosomy
* Lethal or phenotypic effects likely
83
What is a **retrovirus**?
A retrovirus is a type of virus that inserts a copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell.
Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus.
The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus
84
What types of genome changes are most likely to lead to **altered gene function** and WHY?
Various types of mutations in the gene (coding, splice junctions, etc), promoter or flanking regions with controlling elements; if the amount of protein is affected (eg gene expression or nonsense mutations) or if the type of protein is affected (eg missense), then the function or product (product) of the gene will be altered, respectively
85
What types of genome changes are most likely to lead to **new species** and WHY?
Large scale changes such as aneuploidy (including chromosome duplication), ploidy, translocations, chromosomal rearrangements which result in **reproductive isolation** because the progeny of parents with different chromosome complements will be infertile due to errors in meiosis
86
What types of genome changes are most likely to lead to **new genes** and WHY?
Random mutations, alternative splicing, exon/intron shuffling, gene duplication with subsequent mutations, mobile elements; rearrangements or mutations of existing genes can give rise to new genes particularly if the genes or exons have been duplicated but collecting random mutations in a segment of DNA can create new genes, too, but this is rare
