I. Chromosome mutations (chromosomal aberrations)
A. Detect by
1. Microscopic examination
a. Drosophila polytene chromosomes
b. 1000+ copies of chromosome side by side
c. Able to detect fine bands - ~30,000 bp/band
2. Genetic analysis
3. Or both
B. Many cause
abnormalities in cell and organismal function
1. Many involve breakage of chromosome
2. If in gene, gene is inactivated
C. Position of
nucleolar organizers
1. Where nucleoli are found
2. Sequences coding for RNA
3. Help to pinpoint certain areas
D. Broken ends
of chromosomes are highly reactive ‘sticky' - bind anywhere
1. May be due to heat, ionizing radiation, chemicals, viruses, transposons,
errors in recombination
E. Telomeric
ends don't attach to others
II. Deletions
A. Interstitial
- break within chromosome
B. Terminal -
at one end
1. Must have telomere, so probably two breaks
2. Intragenic deletions
a. Appear to be similar to point mutation
b. But not revertible
C. Multigenic
deletions
1. Involve more than one gene
2. More severe consequences
3. If homozygous, almost always lethal
D. Detection
of deletions
1. Deletion loops in meiosis
2. Assign specific location on chromosome
E. Properties
of deletions
1. Failure to survive as homozygote
2. Can not revert to normal
3. If deletion involves centromere, acentric chromosome: won't survive
mitosis
4. Recombination frequencies of genes flanking region are reduced
5. Unmasks recessive alleles on other homolog
a. Heterozygous - effectively haploid in that region
(1) Upsets balance of genes
(2) Recessive genes on other chromosome expressed
(a) Lethal
(b) Deleterious
b. Called pseudo dominance
(1) Use concept in reverse to map deletions
(2) Chromosome with multiple recessive alleles
(3) Those that are expressed in heterozygote
(a) Indicate extent of deletion
(b) Pinpoint deletion that can't be seen
(4) Use deletions (visible) to pinpoint location of genes
F. Deletions
of specific portions of human chromosomes
1. Phenotypic expression as specific syndromes
a. Cri-du-chat syndrome portion of 5p missing (p. 157)
b. Prader-Willi syndrome portion of 15q missing
(1) Poor suckling, weak
(2) Compulsive eater by 5-6
2. Can occur spontaneously
3. Or balanced translocation in parent, not balanced in offspring
III. Duplications
A. Types
1. Tandem
2. Reverse
B. Duplicate
gene free to undergo gene mutation
C. Often formed
simultaneously with deletions
1. From unequal crossovers
2. May get higher order duplications from crossovers
D. Hemoglobin
genes
1. Two subunits ,
2. Each subunit part of multigene family
3. Duplication, then all but one gene mutated
4. Evolutionary advantage
E. Duplications
hard to detect and are rare
1. Also seen as loops in meiosis
2. Can affect recombination frequency of surrounding genes
IV. Inversions
A. Types
1. Pericentric (around centromere)
2. Paracentric (one side of centromere)
B. Some genes
may be turned off
1. Break occurs within gene
2. Other times break between genes
a. Inversion can be made homozygous
C. Recognition
1. Inversion loops in meiosis
2. Altered crossover frequencies
a. Regions outside inversion to inside inversion change distances
b. Mechanical constraint in inversion for crossovers to occur
(1) reduced frequency within inversion loop
c. Changes in chromosome arm lengths (pericentric)
D. Paracentric
crossovers
1. Result in double centromeric chromosome
a. leads to broken chromosomes
b. lethal
2. And acentric chromosome
3. Therefore crossover products not recovered
E. Pericentric
crossovers
1. Not recovered
2. Crossovers result in genetic imbalance
a. ABCD and ACBD - if crossover between B and C
b. ABBD and ACCD - missing and duplicated regions
F. Homozygous
inversions
1. Crossovers not inhibited
2. But linkage map is unusual
G. Use of inversions
to create duplications of particular regions of DNA
V. Translocations
A. Nonhomologous
chromosomes change parts
1. Reciprocal translocations
2. Usually because of breaks due to ionizing radiation
3. Recall that nontelomeric ends are sticky
4. Can also have one chromosome break and attach to a second (nonreciprocal
translocation)
B. Consequences
1. Difference in appearance
a. Length
b. location of centromeres
c. Banding
d. Pairing in meiosis: cruciform structure
2. Different linkage relationships
a. Especially if genes close to break point
b. If multiple genes, can get cross shaped linkage map
3. Meiosis
a. If both translocated chromosomes to same gamete
(1) Alternate segregation
(a) Balanced translocation
(b) No effect
(c) But can lead to adjacent 1 segregation next generation
(2) Adjacent 1 segregation
(a) Adjacent nonhomologous chromosomes to same pole
(b) Massive loss and duplication of genes
i) Nonviable
ii) Semisterility
a) Plants abort at gamete
b) Animals abort at zygote
(3) Adjacent 2 segregation
(a) Adjacent homologous chromosomes to same daughter
(b) Rarely occurs
(c) Always inviable
4. Note that inversions, deletions also show some reduced fertility, but
not as drastic (in
translocation, typically ~50% reduction in fertility)
a. If deleted/duplicated segments are small, may survive
C. Results of
viable translocations
1. Down's syndrome
a. Usually anomaly of extra chromosome 21
b. Non-familial due to non-disjunction
c. Sometimes familial
(1) Due to Robertsonian translocation
(2) Long arms of two acrocentric chromosomes join
(3) End up with two normal 21s and one attached to 14
2. Some types of cancer
a. Sometimes because of location in transcription ‘hot zone'
b. Position effect - where appears affects expression
3. Can be used in generating duplications and deletions for genetic study
4. Can study evolutionary trends by looking at chromosomes of related species
VI. Fragile Sites and Fragile X Syndrome
A. Narrowing
in chromosome; prone to breakage
1. Most notably fragile X syndrome
a. Due to multiple repeats of base sequence CGG
(1) Normal: 6-54 repeats
(2) Premutation: 55-200 repeats
(3) Syndrome: 200-1300 repeats
b. Amplification in female only
c. Probably recombination that causes amplification
2. Other diseases with triplet amplification
a. Myotonic dystrophy
b. Spinobulbar muscular atrophy
c. Huntington disease
d. Because these are not on X chromosome, amplification occurs in both
sexes
VII. Aberrant Euploidy
A. Terminology
1. Monoploid number
2. Euploidy
a. Multiples of monoploid number
b. Haploid, diploid commonly used
c. Note: haploid = monoploid
3. Polyploid
a. Diploid
b. Triploid
c. Tetraploid
d. Pentaploid
e. Hexaploid
B. Monoploid
examples
1. Plants go through monoploid and diploid stages in cycle
a. Plants tolerate changes in numbers of chromosomes quite well
b. Useful technique
(1) Gamete induced with hormones to grow
(2) Use of colchicine in mitosis inhibits spindle fiber formation
(3) Doubles chromosome number
(4) results in diploid plant homozygous for all loci
2. Few animal examples
a. Some insects
(1) Males formed from unfertilized eggs
(2) Parthenogenesis
(3) Sexual reproduction without meiosis in males
C. Polyploids
1. Autopolyploids
2. Allopolyploids
D. Autopolyploids
1. Triploids
a. Usually sterile
(1) Seedless grapes, bananas, watermelon
(2) Plant endosperm
b. Genome imbalance
(1) Improper pairing at meiosis
(2) Univalent and bivalent
c. Humans 15-20% of all miscarriage; 0.01% live births;
(1) most die ~1 month
(2) large head, many anomalies
2. Tetraploids
a. Higher dosages of ALL genes
b. Everything is bigger - cells, flowers, etc.
c. Humans 5% miscarriage
E. Allopolyploids
1. Cells from two organisms fuse
2. Chromosomal pairing at meiosis - each chromosome has pair from same
organism
3. Cabbage - radish
4. Wheat (hexaploid) - 3 related species fused; each with 14 chromosomes
(N=7)
5. Usually have to be closely related species, or begin losing chromosomes
from one of ‘parents'
6. Somatic allopolyploids
a. Can be done using protoplast fusion
F. Polyploidy
in animals
1. not as common
2. Flatworms, leeches, brine shrimp
a. Reproduction by parthenogenesis
3. Amphibians and reptiles, some fish
4. Humans - arise
a. Most die in utero
b. Few are born, but do not survive
5. Mammalian liver tissue
VIII. Aneuploidy
A. Nullisomics
(2n - 2)
1. Usually doesn't survive because essential genes on each chromosome
2. Missing one entire chromosome pair
3. This is possible if 4n - 2 or 6n - 2 (eg. Wheat)
B. Monosomics
(2n - 1)
1. Deleterious
2. Meiosis - remaining chromosome missing pairing partner
3. Gene balance altered
4. hemizygous - expression of all recessive traits
5. Occur often by nondisjunction
6. Turner syndrome (XO in humans)
C. Trisomics
(2n + 1)
1. Chromosomal imbalance
2. Occur often by nondisjunction
3. Abnormality or death (extra dose of genes on chromosome)
4. Down syndrome (trisomy 21)
5. Klinefelter syndrome (XXY)
6. Also trisomy 18 - die within 6 months
a. Edwards syndrome
b. Multiple congenital malformations
c. Often die from cardiac complications
7. Trisomy 13 - die within 3 months of birth
a. Patau syndrome
b. Small eyes, polydactyly, mental and developmental retardation, cardiac
anomalies
D. Disomics (n
+ 1)
1. Haploid genome with one diploid chromosome
E. Somatic aneuploids
1. Spontaneously arise - result in mosaics
For questions, comments
and additional information, contact mfhicks@pstcc.edu
Last Updated: June 23
2001
Site map: Margaret
F. Hicks Home - Biology 2120 -
Notes
- Chromosomal Aberrations
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