Chromosomes Flashcards
1
Q
What is cytogenetics?
A
The examination/visualization of chromosomes
2
Q
What do these terms mean?
- Metacentric
- Submetacentric
- Acrocentric
- Telocentric
A
- Metacentric: centromere is in the middle of the whole chromosome
- Submetacentric: centromere is skewed slightly to one side of the chromosome
- Acrocentric: centromere is skewed to one side of the chromosome
- Telocentric: the centromere is at one end of the chromosome
3
Q
What is the nomenclature of a human karyotype?
A
Lists in order:
- Number of chromosomes per cell
- Complement of sex chromosomes
- Any abnormal chromosomes
4
Q
What is the nomenclature of a human chromosome?
A
Lists in order:
- Chromosome number
- p- short arm or q- long arm
- The region of the arm
- The band number
e. g. 7q36 (chromosome 7, long arm (q), region 3, band 6
5
Q
What are the two methods to distinguish between chromosomes?
A
- G-banding:
- Chromosomes are treated with agent to loosen DNA-protein interaction
- Giemsa stain is added making light and dark bands - FISH (chromosome painting):
- A probe that contains many sequences from an individual chromosome is labelled fluroscently
- The probe is then hybridised the the chromosome in situ
6
Q
What are the sex determining systems of:
- Mammals
- Birds
- Lizards
- Snakes
- Alligators and turtles
- Drosophila
- Grasshoppers
- Wasps, bees and ants
A
1. Mammals: Female: XX Male: XY (Y determines male sex) 2. Birds: Female: ZW Male: ZZ 3. Lizards: Female: XX Male: XY 4. Snakes: Female: ZW Male: ZZ 5. Alligators and turtles: Female: high temp Male: low temp 6. Drosophila: Female: XX Male: XY (1 copy of X determines male sex) 7. Grasshoppers: Female: XX Male: X 8. Wasps, bees and ants Female: diploid Male: haploid
7
Q
What is X-inactivation?
A
- X-inactivation is the process by which randomly one of the two X chromosomes in female cells is inactivated
- This is to compensate for differences in gene dosages between males and females (most genes on X are not involved in sex differences)
- Early in female development an X chromosome in each cell will be randomly inactivated and this inactivated state is propagated to all progeny cells
- Therefore females with X-linked dominant disorders are mosaics
8
Q
What is the mechanism of X-inactivation?
A
- Initiation:
- A region of the X chromosome (Xq13) called the X inactivation centre (Xic) encodes the gene XIST (X-inactive specific transcript)
- Xic is expressed only on the inactive X - Spreading:
- The XIST RNA is not translated but spreads out and coats the inactivated X, this ensures most genes (all but 15% are inactivated- the pseduo-autosomal region) - Maintenance:
- X inactivation is maintained by continued XIST expression in the Barr body in interphase
9
Q
How are human genes mapped to chromosomes using somatic cell hybrids?
A
- An interspecies hybrid cell can be made from fusing the somatic cells of a human and another animal e.g. mouse
- In interspecies hybrid cells the chromosomes of one or other parent are progressively and randomly lost to bring the chromosome number down to a normal number
- By identifying cell lines in which all the other species e.g. mouse chromosomes are retained and only one or two human chromosomes genes can be mapped
- This is done by detecting the presence of a gene product e.g. via an assay, in certain cells and correlating this to the presence of the human chromosome
10
Q
What is aneuploidy?
A
- Aneuploidy: loss or gain of one or more entire chromosomes
- Euploid: normal chromosome complement
- Monosomic: loss of one chromosome
- Trisomic: gain of one chromosome
11
Q
What is the difference between the pair of chromosomes that are a result of non-disjunction at meiosis 1 vs non-disjunction at meiosis 2?
A
Non-disjunction at meiosis I:
- The gamete is given two copies of a chromosome from different homologs
Non-disjunction at meiosis II:
- The gamete is given two copies of a chromosome from the same homologous chromosome pair
12
Q
Why do aneuplodies cause an abnormal phenotype?
A
- The mutations are a result of the products of genes being out of balance
- Monosomy is more abnormal than trisomy
- Aneuploidy is more severe for larger chromosomes than smaller chromosomes (it is more likely that there are more important dosage sensitive genes on that chromosome)
- Severe imbalance leads to in-viability
13
Q
What are two reasons why monosomy of autosomes is inviable?
A
- Many genes are haploinsufficient so 50% of gene activity is not enough for function
- When there is only one copy of a chromosome many recessive mutations on chromosomes will cause problems as there is not a second chromosome to compensate
14
Q
Why are autosomal aneuploids more frequent among offspring of older women?
A
- The maternal age effect:
The spindle may be less efficient with the aging of the cells
15
Q
What is Down Syndrome?
A
Trisomy 21:
- most common and least detrimental autosomal trisomy
- Low IQ
- Characteristic facial features (broad flat face)
- Short stature
- Congenital heart disease and Alzheimers
- Lifespan 60 years
- Region 21q22.2 is the down sydrome critical region
16
Q
What is Edward’s Sydrome?
A
Trisomy 18:
- Growth failure
- Skull elongation
- Mental retardation
- Life span (few days to few months)
17
Q
What is Patau Sydrome?
A
Trisomy 13:
- Growth failure
- Cleft palate
- Harelip
- Polydactyly
- Life span (few days to few months)
18
Q
Why are aneuploidies of sex chromosomes less severe than autosomal aneuplodies?
A
- X-inactivation of most of excess X chromosomes
- Very few genes on Y chromosome
- Phenotype is mainly from pseduoautosomal regions of X and Y (not inactivated in X)
19
Q
What are the 4 common Sex chromosome Aneuploidies?
A
- Turner Syndrome:
45, X, Female: Viable, non-fertile (ovaries degenerate)
Phenotype: short, webbed neck - Triple X:
47, XXX, Female: Viable, fertile - Klinefelter Syndrome:
47, XXY, Male: Viable, non-fertile (testes from but no spermatogonia)
Phenotype: tall, slightly lower IQ, small testes, female pattern body hair - Double Y:
47, XYY, Male: Viable, fertile
20
Q
How do double Y and triple X individuals produce normal gametes?
A
- During early development of the germ cells the normal karyotype is restored
- This occurs because the extra sex chromosome is lost through non-disjunction or lagging during early mitosis
21
Q
What is uniparental disomy?
A
- Both pairs of a homologous chromosome are inherited from one parent
- Usually originates as a trisomy, zygote has 2 copies of chromosome from one parent and one copy from the other
- One of the copies is lost (the copy from the parent that only contributed one)
- Therefore the child has inherited both copies of chromosome from one parent
- If the N.D in one parent is in meiosis II and they are a carrier of an recessive disorder this can result in the child being affected with only one parent being a carrier
22
Q
Can aneuploidy occur during mitosis?
A
- Yes
- Change is permanent and present in all descendent cells
- Leads to a mosaic organism
23
Q
What are the 4 common types of changes in chromosome structure?
A
- Deletion (segment missing)
- Duplication (segment is repeated
- Inversion (change in direction of genetic material along region of chromosome)
- Translocation (segment of one chromsome becomes attached to a different chromosome- or different site on the same chromosome)
24
Q
What are the results of chromosome structure changes?
A
- An abnormal chromosome only survives mitosis/meiosis if it still have one centromere and two telomeres
- Rearrangements can be:
1. Balanced: no gain or loss of genetic material, chromosome complement is complete. Often harmless unless breakpoint disrupts vital gene. Heterozygotes at risk of producing offspring with unbalanced complement
- Unbalanced: gain or loss of genetic material- serious effect on organism
25
What is a deletion?
- A loss of part of a chromosome resulting in effective 'monosomy' for just that segment
- Usually determental, deletion of more than 2% of total haploid genome is fatal
- Defects are due to haplo-insufficiency of one more more genes
26
What is a duplication?
- A segment of a chromosome is repeated
- Mostly caused by abnormal crossing over if chromosomes mis-pair due to presence of repeated sequences in genome (likely to occur in regions of repeats e.g. STRs)
- Many small duplications have no effect (and are retained)
- Gene duplication is critical in generating diversity
27
What are inversions? What are the two types?
- Two breaks in a chromosome occur, the internal region rotates 180 and then the broken ends heal
- The region between the breaks is inverted
- Two types:
1. Pericentric: centromere is inside inverted region
2. Paracentric: centromere is outside inverted region
28
What are the effects of inversions?
- As inversions are balanced, there is often no effect on phenotype
- Effects arise from:
- Breakpoints disrupting important genes
- Individuals heterozygous for an inversion have a variable risk of producing unbalanced gametes
29
How does meiosis occur in an individual heterozygous for a pericentric inversion?
- An inversion loop forms
- If no crossover in inverted region occurs:
1/2 gametes inverted chromosome
1/2 gametes normal chromosome
- all balanced and normal
- If a crossover occurs:
1/4 gametes normal chromosome
1/4 gametes inverted chromosome
1/2 gametes have duplication and deletion
- Therefore 50% of gametes are inviable (unbalanced)
- Causes reduced fertility
- The larger the inversion, the more likely for crossovers to occur
- As crossovers create inviable gametes, no recombination between genes in inverted region occurs
30
How does meiosis occur in an individual with a paracentric inversion?
- Crossover within inverted segment results in recombinant chromosomes that are either acentric or dicentric
- Acentric chromosomes cannot attach to spindle and are lost
- Dicentric chromosomes form dicentric bridges during meiosis and will break resulting in variable deletion
- Causes reduced fertility
- The larger the inversion, the more likely for crossovers to occur
- As crossovers create inviable gametes, no recombination between genes in inverted region occurs
31
What is a translocation? What are the two types?
- A translocation is a transfer of genetic material between two non homologous chromosomes
- Two types:
1. Reciprocal: breaks and exchanges occur between two chromosomes
2. Non-reciprocal: one chromosome gains material and the other loses
32
What causes reciprocal translocation?
1. Chromosome breaks: broken ends lack telomeres and are reactive and may region incorrectly
2. Abnormal crossing over between non-homolgous chromosomes
33
How does meiosis in individuals heterozygous for reciprocal translocations occur?
- The two pairs of chromosomes form a translocation cross/quadrivalent
- They are then segregated by:
1. Alternate segregation (50% of time):
1 and 2 together, der1 and der 2 together.
1/2 gametes normal chromosomes. 1/2 gametes translocation chromosomes (all balanced)
2. Adjacent I segregation (50% of time)
1 and der 2 together, der1 and 2 together.
All gametes duplicate and deficient (unbalanced)
2. Adjacent II segregation (very rare)
1 and der 1 together, 2 and der2 together.
All gametes duplicate and deficient (unbalanced)
- Therefore people heterozygous for these translocations produce only 50% viable balanced gametes
34
What are Robertsonian Translocations?
- A type of non-reciprocal translocation unique to acrocentric chromosomes
- The short arm of one acrocentric chromosome is exchanged with the long arm of another- producing one new large metacentric fusion chromosome and a fragment that is lost
- Chromosome number is reduced
35
What effect do inversions and translocations on evolution?
- Inversion and translocation mutations if they arise and spread promote speciation
- This is because being heterozygous for these mutations causes decreased fertility, so it is advantageous for those homozgyous for the mutation and those homozgyous without the mutation to interbreed only with each other
- This favours reproductive isolation
36
What is an iso-chromosome?
An iso-chromosome is caused by a non-characteristic break at the centromere of a chromosome causing the loss of one arm of the chromosome and the duplication of the other
37
What is fragile X syndrome?
- A mutation in the X chromosome in which there is a section of the chromosome (near telomere at Xq27.3) that causes a fragile site at the gene FMR-1
- The mutation is an increase in CCG repeats in the FMR-1 gene
- The repeats cause the FMR-1 gene to be methylated, the greater the number of repeats, the less function of the gene
- This fragile site is liable to break
- It can be visualized as a non-staining gap
- Causes high forehead, large ears, connective tissue weakness and moderate-severe learning difficulties
- Female carriers sometimes show some facial features and have mild learning difficulties
- So it is considered dominant but with incomplete penetrance
38
What is a polyploid?
- An individual with more than two sets of haploid chromosomes in their somatic cells >2n
e. g. triploid = 3n
e. g. tetraploid = 4n
39
What are the two categories of germline polyploidy?
Autopolyploids: more than two sets of chromosomes, all derived from one ancenstral species
Allopolyploids: more than two sets of chromosomes, derived from more than one ancenstral species
40
What is autotetraploidy? What causes it?
Autotetraploidy (4n): arises as an accident during mitosis where the chromosomes replicate but the cell does not divide. Occurs mainly in plants
- All daughter cells of this original cell are irreversibly autotetraploid
- If the 4n cell are part of the germ line, gametes that arise are diploid and if they self-fertilise they will generate a fully tetraploid plant
41
What is the phenotype of autotetraploids?
- The chromosome complement is balanced so the plant is fully viable (chormosomes pair by bivalents or a quadrivalent during meiosis)
- The cells/tissues/organs are much larger but grow more slowly
- Other than that the autotetraploid closely resembles the diploid
- Once produced is an instant new species (can no longer breed with diploid)
42
What is an autotriploid?
- Arises if a diploid gamete (2n)- from autotetraploid plant or non-disjunction during meiosis, joins with a haploid gamete (n)
- The chromosome complement is balanced- in plants often fully viable
- Usually completely sterile (meiosis in 3n = unbalanced gametes)
Advantages:
- Sterile = no seeds
43
How do allopolyploids arise?
- Haploid complements of species 1 (n=A) and species 2 (n=B) combine to produce an alldiploid interspecies hybrid 2n = AB (nearly always sterile)
- The chromosome number of the interspecies allodiploid hybrid (AB) is doubled during mitosis making an allotetraploid (AABB)
- The resulting allotetraploid cells can form bivalents and balanced diploid gametes will result- making it fertile
- Once produced this allotetraploid is fertile and reproductively isolated from both ancestral species so is an instant 'new' species
44
What is somatic polyploidy?
- Normal variation from euploidy in certain tissues within an animal
e. g. Human liver cells can be 3, 4s, or 8n.
- The purpose of somatic polypoloidy is unclear but it is perhaps to produce very high levels of certain gene products or to generate large cells
