large-scale chromosomal changes Flashcards
(90 cards)
1
Q
two main themes underlying the observations on chromosomal changes
A
- karyotypes generally remain constant within a species
- most genetic imbalances result in a selective disadvantage - related species usually have different karyotypes
- closely-related species differ by only a few rearrangements
- distantly-related species differ by many rearrangements
- correlation between karyotypic rearrangements and speciation
2
Q
x =
A
number of different/unique chromosomes that make up a single complete set
eg 23 in humans
3
Q
n =
A
number of chromosomes in a gamete
eg 23 in humans
4
Q
relation between n and x in diploids
A
n = x
- each gamete contains a single complete set of chromosomes
5
Q
relation between n and x in hexaploids
A
n = 3x
6
Q
euploidy
A
A condition where a cell has a complete set(s) of chromosomes.
7
Q
aneuploidy
A
A condition where a cell has an abnormal number of individual chromosomes, not involving whole sets.
8
Q
give 4 examples of euploid
A
monoploidy (x)
diploidy (2x)
triploidy (3x)
tetraploidy (4x)
9
Q
using diploid species as a basis, explain:
- euploidy
- nullisomy
- monosomy
- trisomy
A
euploidy: 2n
nullisomy: 2n-2
monosomy: 2n-1
trisomy: 2n+1
9
Q
monoploidy
A
- male bees, wasps, and ants
- they undergo parthenogenesis
- usually lethal in other organisms
10
Q
parthenogenesis
A
development of unfertilised egg into an embryo (with no fertilisation):
- single set of chromosomes
- produce gametes by mitosis
11
Q
why is monoploidy lethal in most organisms?
A
- unmasks recessive lethal alleles (eg X-linked diseases)
- if an individual survives to adulthood, this most likely leads to sterility
12
Q
uses of monoploid plants
A
- visualize recessive traits directly
- introduction of mutations
13
Q
how can we create a monoploid plant?
A
- take a diploid plant
- haploid pollen grains are treated and plated onto agar
- growth of haploid embryoids
- embryoids treated with plant hormones
- monoploid plant (usually sterile)
14
Q
what is the issue with having a monoploid plant?
A
- in meiosis, chromosomes are supposed to pair up and separate.
- in monoploids, there’s nothing to pair with, so meiosis is disrupted, leading to infertile gametes.
15
Q
how is colchicine useful to scientists?
A
- colchicine inhibits the formation of the mitotic spindle
- thus the plant cells become diploid and meiosis is able to occur normally
16
Q
in what organisms is polyploidy particularly common?
A
in plants
17
Q
tetraploidy in plants
A
alfalfa, coffee, peanuts, large apples, pears, grapes
18
Q
octoploidy in plants
A
large strawberries
19
Q
results of polyploidy in plants
A
- associated with origin of new species
- may positively correlate with size and vigor
20
Q
two types of polyploids
A
- autopolyploids
- allopolyploids
21
Q
autopolyploids
A
- originate within a species
- all polyploids with an odd number of chromosome sets are sterile because they cannot produce balanced gametes, producing aneuploid gametes
22
Q
when can autopolyploids with an odd number of chromosome sets produce balanced gametes?
A
- if x is small
- balanced gametes are only produced if two copies of each chromosome always segregate to the same daughter cell and the third to the other
23
Q
generation of autotetraploids
A
- when the 2x genome of a diploid is doubled to 4x, with all four sets coming from the same species
- could be spontaneous or induced by a drug such as colchicine
- often the source of a new species
24
how are balanced gametes generated in autotetraploids?
- each chromosome has three homologs to choose from
- in order to form balanced gametes, the four copies of each group of homologues must form two bivalents
- successful tetraploids produce balanced 2x gametes and are fertile
25
allopolyploids
- hybrid of two or more closely-related species
- partially homologous chromosomes
26
amphidiploid
doubled diploid: contains two different diploid genomes
27
amphipolyploids in agriculture
F1 hybrid of wheat and rye (triticale) is sterile because there are no pairing partners for the rye chromosomes
28
describe the different triticale hybrids that have been generated
- some combine high yield of wheat with ability of rye to grow in unfavourable environments
- some combine high level of protein from what with high level of lysine from rye
29
4 examples of aneuploidy in sex chromosomes
XXY, XXX, XO, XYY
30
draw diagrams for nondisjunction during the first and second meiotic division, as well as after fertilisation by a normal gamete
31
what are the potential consequences of mitotic nondisjunction?
can result in a mosaic - am individual has two or more populations of genetically different cells in their body.
32
gynandromorph
an organism that has both male and female physical characteristics — often with distinct regions of male and female tissues
33
two types of mitotic nondisjunction
1. mitotic nondisjunction
2. mitotic chromosome loss
34
why do fertile aneuploids generate aneuploid progeny?
offspring of fertile aneuploids have an extremely high chance of aneuploidy because of production of unbalanced gametes
35
aneuploidy in the human population
- incidence of abnormal phenotypes caused by aberrant chromosome organisation or number is 0.4%
- half of spontaneously aborted foetuses have chromosome abnormalities
- incidence of abnormal phenotypes caused by single-gene mutations is 0.01%
36
monosomy in humans
2n-1; usually lethal in utero in humans, but there are a few exceptions:
- Monosomy 21: born with severe multiple abnormalities but die shortly after birth
- Turner Syndrome (XO): 99% of affected foetuses are not born. Those who are born have developmental abnormalities
37
defining characteristics of Turner Syndrome
short stature, sterile due to rudimentary ovaries and lack of menstruation
38
X inactivation occurs in XX individuals, so why are there abnormalities in XO individuals?
- embryogenesis: X inactivation occurs after several rounds of cell division, so it is thought that the 2nd X chromosome has important function within the first hundred divisions
- some of the genes on the 'inactivated' X chromosome are expressed
- germ-line: X chromosome reactivation
39
trisomy in humans
2n+1: often lethal in animals owing to chromosome imbalance
40
trisomy 21
Down syndrome
- females can be fertile
- males infertile
- average life expectancy is 40-60 years due to congenital heart disease
41
trisomy 18
Edward syndrome
- severe physical and mental abnormalities
- heart defects, growth retardation, small jaw, kidney abnormalities, narrow pelvis, rocker bottom feet, clenched fists
- average life expectancy of a few weeks
- 1/6000 to 1/10000 live births
42
trisomy 13
patau syndrome
- severe physical and mental abnormalities
- major abnormalities of heart kidneys, brain, face and limbs, small or absent eyes, harelip, small malformed head
- average life expectancy of 130 days
- 1/12500 to 1/21700 live births
43
three types of sex chromosome trisomies
XYY
XXX
XXY (Klinefelter syndrome)
44
Klinefelter syndrome
1/1000 male births
- humans tolerate X chromosome aneuploidy because of X inactivation
- sterile
45
why can aneuploidy for X have phenotypic consequences?
some X-linked genes escape inactivation — especially those in the pseudoautosomal regions (PARs). One key gene, SHOX, is essential for bone growth. Loss (like in Turner syndrome) or gain (like in XXX or XXY) of SHOX copy number leads to short or tall stature, respectively.
46
prenatal diagnostic testing
- look for abnormal karyotypes
- possible to screen for biochemical and genetic disorders
- tests are done in combination with blood tests for certain maternal and fetal proteins, and with ultrasound tests
47
prenatal testing - screening tests
first trimester screening test (11 to 13 weeks) ultrasound (nuchal translucency) and maternal blood test [pregnancy associated plasma protein-A (PAPP-A) and β-human chorionic gonadotrophin (β-hCG)]
48
prenatal testing - diagnostic tests
- chorionic Villi Sampling, CVS (10 to 13 weeks)
- amniocentesis (16+ weeks), less invasive
49
which comes first - screening tests or diagnostic tests
screening tests - if there are abnormalities, we then conduct diagnostic tests.
50
how does chromosome rearrangement represent a major feature of evolution?
1. rearrangement breakpoint may acquire new patterns of gene expression and create new gene functions by fusion of two separate genes
2. some rearrangements contribute to the process of speciation
3. duplications provide extra gene copies that can acquire new functions
51
state and draw the four classes of chromosomal rearrangements resulting from chromosome breakage and subsequent DNA repair
- deletion
- inversion (180 degree rotation of a piece of DNA)
- deletion in one chromosome, duplication in another
- translocation of a piece of DNA into another chromosome
52
state and draw the four types of chromosomal rearrangements resulting from aberrant crossing over at repeated sequences
- deletion
- inversion
- deletion in one chromosome, duplication in another
- reciprocal translocation of a piece of DNA into another chromosome
53
two types of deletions
1. intragenic: small deletion within a single gene
2. multigenic: many genes deleted
54
Del (Df) homozygotes
- short for deletion (deficiency) homozygote, is an individual that has both copies of the same chromosomal region deleted
- usually inviable
55
Del (Df) heterozygotes
- gene imbalance
- might result in haploinsufficiency
56
deletion loop
a DNA loop formed during meiosis when one homologous chromosome has a segment deleted. The extra DNA on the normal homolog that has nothing to pair with loops out.
57
pseudodominance
when a recessive allele is expressed in a heterozygous individual because the dominant allele has been deleted or is missing.
58
what is a practical application of deletions?
- deletions may uncover recessive mutations
- they can be used to locate genes for mapping
59
deletion mapping: complementation
1. Start with a mutant strain that has a recessive mutation (e.g. mut) causing a known phenotype.
2. Cross it with a strain that carries a known deletion of part of the chromosome (e.g. Df1).
3. Examine the phenotype of the offspring (heterozygotes: mut / Df1):
- If the offspring show the mutant phenotype, then the deletion likely removes the same gene as the mutation → No complementation.
- If the offspring show the wild-type phenotype, the mutation must lie outside the deleted region → Complementation occurs.
60
two main types of duplications
tandem duplications: the duplicated segment is inserted right next to the original.
non tandem (dispersed) duplications: the duplicated segment is inserted elsewhere in the genome, not adjacent to the original.
61
impact of duplications
- less likely to affect phenotype
- in some cases causes a dosage effect/genetic imbalance
- genes may be placed in a new location that modifies their expression
62
how do duplications arise?
1. X-ray breaks/any other cause of breaks:
- X-rays break one chromosome in two places
- X-rays break homologous chromosome in one place
- during repair, the freed segment from the first chromosome is mistakenly inserted at the break site on the homolog -> non tandem duplication
2. Unequal crossing over:
- Homologous chromosomes misalign during meiosis.
- Crossing over occurs at these misaligned points.
- One chromosome gains extra DNA (duplication), the other loses it (deletion).
63
duplications can result in
unequal crossing over, causing increase and reciprocal decrease in the number of copies (eg Bar-eye in drosophila)
64
potential impacts of inversions
- most inversions to not alter phenotype unless breakpoints occur within genes
- but genes may be placed in a new location that modifies their expression (eg Antennapedia)
65
two main types of inversion
1. pericentric inversion - includes the centromere
2. paracentric inversion - does not include the centromere
66
breakpoints between genes
- Genes remain intact.
- Order of genes is reversed in the inverted segment.
- Usually no gene disruption or loss of function.
- May affect gene expression if regulatory regions are affected.
67
breakpoints within ONE gene
- The gene is disrupted (split) and mutated
- Usually causes loss of gene function or creates a truncated protein.
- Can lead to a nonfunctional or altered gene product.
68
breakpoints within TWO genes
- Both genes are disrupted at the breakpoints.
- May create fusion genes by joining parts of two genes.
- Can produce novel or dysfunctional proteins.
- Often causes loss of function or gain of abnormal function.
69
inversion loops
- form in inversion heterozygotes
- enables pairing of homologous regions despite the reversed gene order.
- produces abnormal recombinant chromosomes.
70
paracentric inversion loop
Normal chromosome + Inversion chromosome. Inversion loop forms outside the centromere:
- if crossing over occurs inside this loop, it produces one dicentric chromosome (with two centromeres) and one acentric fragment (without a centromere)
- the acentric fragment is lost
- there is a random break in the dicentric bridge of the dicentric fragment
Results in: one normal product, two deletion products, and one inversion product with all genes present. Reduced number of viable gametes
71
pericentric inversion loop
Normal chromosome + inversion chromosome. Inversion loop includes the centromere:
- if crossing over occurs inside this loop, it results in gene imbalance
- one normal product, two different inviable deletion/duplication products, one viable inversion product (all genes present). Reduced number of viable gametes
72
look over how to find the possible gametes arising from a paracentric and pericentric inversion
73
What are balancer chromosomes and why are they useful?
- engineered chromosomes used in genetics that carry multiple inversions and sometimes other rearrangements.
- these prevent crossing over from happening during meiosis
74
translocations
- most translocations do not alter phenotype unless breakpoints occur within genes
- but genes may be placed in a new location that modifies their expression
75
three types of translocations
a) nonreciprocal intrachromosomal translocation
b) nonreciprocal interchromosomal translocation
c) reciprocal interchromosomal translocation
76
cause of chronic myelogenous leukaemia
- arises from a specific reciprocal translocation between chromosomes 9 and 22
- this translocation fuses the BCR gene from chromosome 22 with the ABL gene from chromosome 9, creating the BCR-ABL fusion gene.
- the BCR-ABL fusion produces a constitutively active tyrosine kinase protein that drives uncontrolled cell division and the malignant proliferation of white blood cells seen in CML.
77
3 types of segregation patterns occurring in heterozygotes during meiosis
- alternate
- adjacent-1
- adjacent-2
78
draw a diagram and table for alternate segregation pattern
79
draw a diagram and table for adjacent-1 segregation pattern
80
draw a diagram and table for adjacent-2 segregation pattern
81
consequences of different segregation patterns
- semiysterility since <50% of the time there are viable gametes
- pseudo linkage since genes can't independently assort
- only alternate segregation produces viable progeny
82
robertsonian translocation
reciprocal exchange between acrocentric chromosomes generates a large metacentric chromosome and a small chromosome (which may be lost)
83
robertsonian translocation and Down syndrome
- a parent carries a Robertsonian translocation involving chromosome 21 and another acrocentric chromosome (commonly chromosome 14).
- this carrier has 45 chromosomes but is usually healthy because they have all the essential genetic material.
- however, during gamete formation, abnormal segregation can lead to a child inheriting two normal chromosome 21s plus the translocated chromosome containing an extra copy of 21 material.
- this causes trisomy 21, the genetic cause of Down syndrome.
table
84
methods of detection of chromosomal rearrangements
Fluorescent in situ hybridisation (FISH)
- FISH Karyotype
- Multicolour banding
85
FISH karyotype
- uses fluorescent probes that bind to specific DNA sequences or regions on chromosomes.
- detects presence, absence, or location of specific genes or chromosomal regions.
- useful for identifying known abnormalities (e.g., deletions, duplications, translocations).
- shows bright fluorescent signals on chromosomes under a microscope.
86
Multicolour Banding
- specialized form of FISH that uses multiple probes along a single chromosome to create a unique banding pattern with different colors.
- allows high-resolution analysis of structural chromosome rearrangements.
- can distinguish small intrachromosomal changes like inversions or complex rearrangements.
- provides a detailed “barcode”-like pattern for precise mapping.
87
chromosomes from normal cells vs chromosomes from tumour cells
chromosomes from tumour cells may be present in larger copies
88
detection of chromosomal rearrangements by PCR
- fast
- inexpensive
- highly sensitive
89
give a real world example of how translocations can contribute to speciation
- house mice in the island of Madeira
- different Madeira mouse populations have unique Robertsonian translocations, forming distinct chromosomal races.
- reduced fertility of heterozygotes for translocations can contribute to reproductive isolation and promote speciation
