Ch. 6 Variation in # and Structure of Chromosomes Flashcards
1
Q
Aneuploidy
A
missing or additional single chromosomes
2
Q
Polyploidy
A
additional sets of chromosomes
3
Q
Chromosome mutations - different types
A
Modifications at the level of the chromosomes.
Changes in the total number of chromosomes.
Deletion or duplication of segments of chromosomes.
Rearrangements within or among chromosomes.
4
Q
Chromosomes mutations have an impact on?
A
Phenotypes. Bc genetic component of organisms is a very delicate balance.
5
Q
Changes in location or content of the genetic variation?
A
Changes the phenotype
6
Q
Changes in location or content of the genetic variation in animals and plants?
A
In animals, most such changes are lethal.
Plants are more tolerant - can use this to create plants that are bigger and more viable
7
Q
Cytological analysis steps
A
How to diagnose chromosome mutations.
- Take blood sample
- Separate cells from serum by centrifugation
- Remove white cells and culture in vitro
- Stimulate cells to divide
- Disable mitotic spindle (cells arrested in metaphase)
- Add hypotonic solution to swell cells.
- Squash cells on slide, fix, and stain.
- Examine chromosomes (karyotype)
8
Q
Cytological analysis - different staining techniques
A
Giemsa, quinacrine mustard, reveal characteristic bands; FISH and fluorescent microscopy can reveal locations of genes etc.
9
Q
Human kayrotype
A
p= petite, small arm of chromosome
q= long arm
Use staining techniques to reveal banding pattern. Experienced lab technicians can see if there is a piece of chromosome missing.
10
Q
ploidy
A
“fold” as in “twofold”
11
Q
Euploid
A
“good fold”
Having complete sets of chromosomes (diploid=2n; triploid=3n; tetraploid=4n; polyploid= multiples of n)
12
Q
Aneuploid
A
“not good fold”
Having particular chromosomes of parts under or over represented.
13
Q
Aneuploidy vs polyploidy
A
Aneuploidy implies a genetic imbalance; polyploidy does not.
14
Q
Monosomy
A
2n-1
Loss of a single chromosome in an otherwise diploid organism.
15
Q
Trisomy
A
2n+1
Gain of a single chromosome in an otherwise diploid organism.
16
Q
Autopolyploidy
A
Multiples of the same genome
17
Q
Allopolyploidy (amphidiploidy)
A
Multiples of closely related genomes
18
Q
Aneuploidy
A
variation in chromosome number.
Organisms gains or loses one or more single chromosome.
19
Q
Hypoploid
A
an organism in which a chromosome or chromosome segment is underrepresented
20
Q
Hyperploid
A
an organism in which a chromosome or chromosome segment is overrepresented
21
Q
Nondisjunction causes?
A
monosomy and trisomy
22
Q
Nondisjunction
A
random errors during the formation of gametes.
Paired homologs fail to disjoin during segregation.
Results: normal distribution of chromosomes into gametes is disrupted.
Nondisjunction can happen during meiosis 1 or 2. - outcome is different depending on where.
(homologous chromosomes pair up in meiosis, random error happens and pair fails to disjoin during segregation.
23
Q
Nondisjunction in meiosis 1
A
In metaphase 1, homologous chromosomes don’t separate.
1 daughter has more chromosomes, the other is missing some.
2 gametes are n+1 (extra), 2 gametes are n-1 (missing). No normal gametes.
24
Q
Nondisjunction in meiosis 2
A
In metaphase 2, sister chromatids don’t separate.
1 gamete is n+1 (extra), 1 gamete is n-1 (missing), 2 gametes are n (normal)
25
Fertilized gametes- first division nondisjunction
Can result in either trisomic or monosomic zygotes
26
Fertilized gametes- second division nondisjunction
Can result in disomic (normal), trisomic, or monosomic zygotes
27
Monosomic and trisomic zygotes
Most fail to develop, so frequency is not as high
28
Only known monosomy in humans (in X)
Turner syndrome
29
Monosomy overview
loss of one chromosome (2n-1).
Although one copy remains, if an allele is lethal, organisms is not viable (Monosomy unmasks lethal alleles).
Haploinsufficiency: when one copy of a gene is not sufficient for an organism to survive.
Monosomy of sex chromosomes: Turner syndrome (45,X).
Autosomal monosomy not tolerated in humans or other animals. (causes organism to lose too much genetic material to survive).
In Drosophila, flies that are monosomic for chromosome IV (less than 5% of the organism's genes) develop more slowly, exhibit reduced body size, and have impaired viability.
More common in plants (tabacco, maize) but plants are usually less viable.
30
Trisomy overview
Addition of a chromosome (2n+1).
Trisomies for autosomes are often lethal during development.
Addition of chromosomes produces more viable organisms than monospmy (as long as the chromosomes are small)- depends on the amount of genetic material.
Plant tirsomies are viable. Ex: Datura stramonium with altered phenotype (Jimson weed)
31
Jimson weed
The capsule of the fruit of the jimson weed, the phenotype of which is uniquely altered by each of the possible 12 trisomic conditions
32
Monosomies and Trisomies: impact
depends on the size/information content of the chromosome in question.
Only known Trisomies in humans where baby survives the chromosomes are small and contain less genetic material than large ones.
33
Human aneuploidy
About 20% of all conceptions end in spontaneous miscarriages during early pregnancy (first trimester) very often before she is aware of pregnancy.
About 30% of these show some form of chromosomal imbalance.
In humans, only 3 autosomic trisomies are known to survive to term:
Patau Syndrome (47, 13+)
Edwards syndrome (47, 18+)
Down syndrome (47, 21+) - only one where affected person survives into adulthood.
34
```
Trisomy 21 (Down Syndrome)
s/s
```
Affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate.
Characteristic facial appearance.
Weak muscle tone (hypotonia) in infancy.
Variety of birth defects: about half of all affected children are born with a heart defect.
20 times more likely to develop leukemia.
Alzheimer's disease in older individuals.
35
DSCR: Down Syndrome critical region on chromosome 21
Genes are dosage sensitive.
Responsible for many phenotypic-associated syndromes.
Since 2004: mouse model trisomic for DSCR
Cognitive deficiencies are most likely caused by the presence of 3 copies of DSCR, but other unknown factors many contribute.
Decreased risk of developing cancers with solid tumors, like lung cancer and melanoma.
36
Origin of Extra 21st chromosome
Nondisjunction of chromosome 21 during meiosis.
Homologs do not disjoin in anaphase 1 or 2.
Leads to n+1 gametes.
Ovum is the source of 95% of trisomy cases (means maternally caused)
Increased incidence with increasing maternal age.
Newer research suggest that the paternal age plays role too.
37
Incidence of Down Syndrome syndrome births related to maternal age
```
Trisomies are caused through random nondisjunction for various unknown reasons, but there is a correlation with maternal age (exception: Familial Down syndrome)
35 - 3/1000
40 - 10/1000
45 - 1/30
50 - 1/15
```
38
Down syndrome and age men vs women
In spermatogenesis, gametes are continuously produced from puberty into adulthood.
IN oogenesis, primary oocytes are produced in the female embryo.
Meiosis is arrested in the primary oocytes in prophase 1, ovaries are inactive during infancy and childhood.
Starting with puberty, every month one primary oocyte completes meiosis and becomes an egg.
An egg released by a 40 yr old woman, originates from a 40 yr old oocyte.
Chromosome nondisjunction is more likely to happen in an older egg.
39
Trisomy 13 - Platau Syndrome
Occurs 1 in 16,000 births
Severe intellectual disability and physical abnormalities (hear defects, brain/spinal cord abnormalities, very small eyes).
Many infants with trisomy 13 die within their first days or weeks in life.
Only 5-10% of children with this condition live past their first year.
40
Trisomy 18 - Edward's syndrome
Occurs 1 in 5000 births.
Slow growth before birth and a low birth weight.
May have heart defects and abnormalities of other organs, small abnormally shaped head; many individuals with trisomy 18 die before birth or within their first month.
5-10% of children with this condition live past their first year.
41
Triple X syndrome (XXX)
Occurs in 1 in 1000 females.
Although females with this condition many be taller than average, this chromosomal change typically causes no unusual physical features. Most females with triple X have normal sexual development and are able to conceive children.
42
Jacob's syndrome (XYY)
Occurs in 1 in 1000 male births.
May be taller than average, this chromosomal change typically causes no unusual physical features.
Normal sexual development.
Associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), hand tremors or other involuntary movements (motor tics).
43
Kleinfelter Syndrome (XXY)
Occurs in 1 in 1000 male births.
| Breast development. Wide hips. Female type pubic hair. small testicular size. poor beard growth. few chest hairs.
44
Turner's Syndrome (X0) monosomy
occurs 1 in 2500 female births.
Underdeveloped breasts, widely spaced nipples.
Rudimentary ovaries.
45
Mosaicism
Nondisjunction in mitotic division can generate patches of cells with chromosomal abnormality and patches of normal cells.
50% of persons diagnosed with Turner syndrome are mosaics through mitosis: some cells are 45,X and some cells are 46,XX (normal).
Arises when X chromosome is lost soon after fertilization in XX embryos.
46
Mosaicism in Drosophila (fruit flies)
presence of two XX produces female traits.
Presence of one X produces male traits.
XX/XO mosaics in fruit flies are gynandromorphs.
XX-female traits (red)
X- male traits (white)
47
Polyploidy
Multiple sets of chromosomes are present (more than 2 sets) influences phenotypes
48
Polyploidy
Extra sets of chromosomes: can affect the organism's appearance and fertility.
More than 2 multiples of haploid chromosomes found. (most organisms diploid 2n)
Triploid has 3n
Tetraploid has 4n
Pentaploid has 5n
Polyploidy is rare in animals: probably it interferes with sex-determination mechanism; found in some reptiles, amphibians and fish.
(doesn't necessarily imply there is an imbalance in gene doses, but can affect appearance and fertility)
49
Polyploidy is common in plants
2/3 of all grasses are polyploid (wheat)
1/2 of all plant genera contain at least 1 polyploid species.
Tolerable bc a lot of these species reproduce asexual. (No sex determination mechanism in plants)
50
Polyploidy: Major mechanisms by which new plant species have evolved
40% of all flowering plants
80% of all grasses are polyploid
Polyploid cells are larger
Polyploid species are overall larger, more robust and larger seeds and fruits
Application:
many ornamental garden plants are polyploid
many crop species are polyploid: wheat, oats, cotton, sugar cane, potatoes
51
Origin of polyploidy in plants depends on
if a 2nd species is involved or not
52
Autopolyploids
Addition of one or more sets of chromosomes identical to the haploid complement of the same species
53
Allopolyploids
Combination of chromosome sets from different species as a consequence of hybridization
54
Chromosome doubling is a key event in?
The formation of polyploids
55
Accidents during mitosis or meiosis can create?
Autopolyploids
56
Autopolyploid through mitosis
Replication
Separation of sister chromatids.
Nondisjunction (no cell division).
Autotetraploid (4n)
57
Autopolyploid through meiosis
Replication
Nondisjunction
Homologous chromosome pairs do not get separated.
Results in 2 gametes that are 2n (diploid).
When fertilization occurs, results in triploid (3n) zygote.
58
Accidents during mitosis or meiosis can create autopolyploids
Arises in several ways; failure of all chromosomes to segregate during meiosis/ separate during mitosis.
Each identical set of chromosomes is identical to parent species.
Homologous chromosomes will try to align during prophase 1.
Would lead to gametes with unbalanced chromosomes numbers (even and uneven numbered autopolyploids).
Usually autopolyploids are sterile and do not produce seeds (triploid bananas, watermelons).
(mitotic mechanism interfering)
59
Sterile polyploids
Although larger and more robust, many polyploid plants are sterile.
Extra sets of chromosomes segregate irregularly, leading to unbalanced gametes.
60
Sterile polyploids
| Triploid species
Homologous chromosomes have problem pairing during meiosis. Some gametes will have too many chromosomes, other will be aneuploid.
Such species are cultivated asexually (cuttings, bulbs)
61
Allopolyploids
Arise from hybridization b/t two species.
Hybrid plants may be sterile.
Cannot produce viable gametes.
Chromosomes are not homologous (bc fused from 2 diff species).
Cannot synapse in meiosis.
But: chromosomes doubling can change this, bc it creates even number of chromosome sets (highly sought after when breeding crop species to turn them from sterile to fertile).
62
Fertile polyploids
Distinct sets segregating during meiosis.
Mostly in hybrids of two species of plants (allopolyploids).
1. Gametes from two diploid plants unite to form a hybrid.
2. The hybrid is sterile bc meiosis is highly irregular (A can't pair with B = sterile)
3. The chromosomes are doubled creating a tetraploid (AA BB)
4. Meiosis in the tetraploid is regular. A chromosomes pair with A chromosomes and B chromosomes pair with B chromosomes.
5. The euploid gametes (AB) produced by the tetraploid can combine to propagate the organisms sexually.
63
1920: Georg Karpechenko's experiments with polyploids
Tried to create cabbage/radish hybrid.
Cabbage (2n=18) only leaves are consumed.
Radish (2n = 18) only roots are consumed.
Goal: cabbage radish hybrid would be a waste less plant.
Crosses: hybrids (2n=18) were sterile.
One hybrid produced seeds.
Grew into viable, fertile plants (allotetraploids, 2n=36), but new plants had cabbage roots and radish leaves (opposite of what he wanted).
(Don't have influence over how genes will be expressed. Bc 2 species have same # of chromosomes, doesn't mean that the chromosomes would be homologous)
64
Polyploids in agriculture
In many organisms, cell volume is correlated w nuclear volume, which is determined by genome size increase in chromsomes number -> increase in cell size.
Leads to plants with larger leaves, flowers, seeds and fruits (or seed less plants-watermelon)
65
The origin of hexaploid (6n) wheat
1. Two diploid species (Einkorn wheat AA and wild grass BB) cross to produce a hybrid with 2 different sets of chromosomes in its genome (AB).
2. The chromosomes in the hybrid double to form a tetraploid (AA BB).
3. The tetraploid hybrid (AA BB) crosses with another diploid species (wild grass DD) to produce a plant with three different sets of chromosomes in its genome (ABD).
4. The chromosomes in the triple hybrid double to form a hexaploid (AA BB DD = modern day bread wheat).
Bigger yield. Higher gluten content - for bread you want high gluten content to make dough sticky.
66
Chromosome rearrangements: Changes in chromosome structure
Deletions (deletion of a segment).
Duplications (duplication of a segment).
- total amt of genetic information in chromosome changes.
Inversions (segment inverted by 180 degrees).
Translocations (movements of a segment).
- genetic material is rearranged, but the information content remains the same.
67
Nonreciprocal translocation
AB is broke off and merged with other chromosome.
68
Reciprocal translocation
changes both chromosomes
69
Chromosome deletions
```
Missing regions of chromosomes.
Chromosome breaks in one or more places.
Usually the piece is lost.
Location of deletion can vary.
Terminal deletion (near one end).
Intercalary deletion (interior of the chromosome).
Large deletions can be seen on karyotypes.
In individuals heterozygous for the deletion, homologous chromosomes can still pair during prophase 1 in meiosis (loop formation)
```
70
Effects of deletions:
Depend on which genes are located in the deleted region.
If the deletion includes the centromere, the chromosome will be lost during mitosis/meiosis - monosomy.
Many deletions are lethal in the homozygous state.
Individuals heterozygous for a deletion may have multiple defects:
1. Produces an imbalance
2. Recessive mutation will be expressed if the wildtype allele was lost (pseudodominance).
3. Haploinsufficiency: some genes must be present in two copies, one copy is not enough.
71
Cri-du-chat syndrome Karyotype 46,XY (5p-)
Chromosome 5 - piece of petite arm missing.
"cat cry syndrome" - infants make cat like cries.
The deletion causes severe mental and physical impairment.
FISH- fluorescent probe binds to 5 p arm, only binds to 1 homologous chromosome but not the other bc the piece is missing.
72
Chromosome deletions in humans
Cri-du-chat (46, XY, 5p-)
73
Chromosome deletions in humans
| Wolf-Hirschhorn syndrome (46, XY, 4p-)
cleft lip and palate, severe intellectual disability
74
Chromosome deletions in humans
| Williams-Beuren syndrome (46, XY, 7q-)
heart defects, mental impairment
75
Chromosome deletions in humans
| Prader-Willi syndrome (46, XY, 15 q-)
feeding difficulty at early age but become obese after 1 year of age, mild to moderate intellectual disability
(more common-ppl usually survive)
76
Chromosome duplications
Repeated segment of chromosome, part of the chromosome has been doubled.
Single locus is present more than once in genome.
Effects: unbalance gene doses
Can arise from unequal crossing over between synapsed chromosomes during meiosis.
77
Duplicatons
Crossing over is not in correct location (BCx CD)
| Results in one chromosome ABDEF and the other ABCCDEF.
78
Origin of red green blindness in humans
Red and green opsin genes on X chromosomes, 98% identical.
Chromosomes do not align properly, results in unequal crossing over.
(bc red and green are so similar, crossing over can happen b/t them but in unequal way).
One resulting chromosome has 2 green opsin genes (a duplication) and the other chromosome has no green opsin gene (a deletion).
If a son inherits the X chromosome with the deletion, he will be red green blind (no green opsin).
79
Duplications in evolution
Duplications provide a way for the arousal of new genes.
The extra copy of the duplication is free to undergo mutation.
Humans have a series of genes for different globin chains, some are active as oxygen carriers during adulthood, some during embryonic and fetal development. All of these globing genes arose from an ancestral gens that underwent duplication.
Amylase gene in wolves (one copy) and dogs (several copies) breaks down starch.
Duplications of amylase gene- natural selection during domestication of dogs, could digest more starch diet.
80
Inversion
Rearrangement of a linear gene sequence.
No loss of genetic information.
Segment of chromosome turned 180 degrees within the chromosome.
Requires two breaks in chromosome, and insertion of the inverted segment.
May arise from chromosomal looping.
81
Paracentric inversion
Centromere is not part of inverted segment.
| Does not change lengths of the 2 arms of chromosome.
82
Pericentric inversion
Centromere is part of inverted segment.
Does change lengths of the two arms of chromosome.
Location of centromere changes.
83
Pericentric vs paracentric inversions
Has been studied extensively in Drosophila.
Inversion can be induced in the lab with X-ray irradiation (X-rays can cause chromosomes to break).
Peri - includes centromere. Location of centromere has changes, p arm is bigger and q are is shorter in example.
Para - excludes centromere. Centromere stays in the same place.
84
Pairing between normal and iverted chromosomes
Pairing between homologous chromosomes can still happen during meiosis through a loop formation.
(Can still travel through meiosis and pair up with each other)
85
Effects of inversion
Only the DNA sequence has been altered, but no information is gained or lost.
Still has effect on phenotypes: Genes could break into 2 parts.
Human evolution: g-banding patterns reveal that several human chromosomes differ from those of chimpanzees by only a pericentric inversion.
86
Translocations
Alter the location of chromosomal segments in the genome.
| Occur when a segment from one chromosome is detached and reattached to a different (non homologous) chromosome.
87
Reciprocal translocation
pieces of two non homologous chromosomes are exchanged without any net loss of genetic material.
Bc location has been changed, consequence can be catastrophic in genome.
88
Robertsonian Translocation (centric fusion)
Involves breaks at extreme ends of short arms of two non homologous acrocentric chromosomes.
Small segments are lost.
Large submetacentric or metacentric chromosomes ae produced.
Ex: Familial Down Syndrome (causes 4% of all down syndrome cases) (down syndrome following mendelian rules and is inherited)
89
Robertsonian translocation are formed by
the fusion of two nonhomologous chromosomes at their centromeres.
Results in: q centromere q
p centromere p is lost
90
Translocation carrier
Karyotype of a 21/14 translocation carrier, who is phenotypically normal, but is at an increased risk of having children with down syndrome (familial)
21 only has 1 chromosome, 14 one of the chromosomes is longer so other chromosome 21 ended up on 14
91
Robertsonian translocation: Familial down syndrome
Translocation carrier has a normal phenotype (translocation does not affect gene function).
But during meiosis translocation interferes with segregation.
Zygotes: 1 normal, 1 translocation carrier (phenotypically normal), 1 Trisomy 21 (downs), 1 monosomic (lethal)
92
Fragile sites
| CFS: Chromosomal fragile sites
Constrictions or gaps at particular sites on chromosomes, prone to breakage.
More than 100 fragile sites in human chromosomes
2 types are common and rare
HumCFS: database for fragile sites in humans
93
Fragile sites
CFS: Chromosomal fragile sites
Common fragile sites
Present in all humans, normal feature (often a location for breakage in cancer cells).
(research-might be a way to stop cancer cells from dividing)
94
Fragile sites
CFS: Chromosomal fragile sites
Rare fragile sites
found in only few people, inherited in Mendelian fashion; associated with genetic disorders
95
Fragile - X syndrome (FXS, Martin Bell syndrome)
1 in 3600 to 4000 males
1 in 4000 to 6000 females
X linked inheritance.
Range of intellectual disabilities.
Correlation with Autism Spectrum Disorder.
FMR1: gene at the fragile site - produces protein important for synapses in brain.
FMRP: protein involved in forming synapses.
Gene mutation results in increase in the number of CGG trinucleotides (the higher the number the more severe are the symptoms)
