Chromosomal abberration Flashcards
Chromosomal rearrangements
- Chromosomes are fragile, regions can:
- Break off (and sometimes re-join another chromosome)
- Invert
- Duplicate
- Changes to chromosome structure have varied phenotypes
- Sometimes nothing happens – especially if balanced
- Sometimes disease results
Chromosomal fragile sites
• Chromosomes are littered with tiny gaps or ‘pinches’ which tend to break
• Not prone to spontaneous breaks
biological/ reproductive stressor such as - alcohol and
• Unless other factors influence chromosomal instability
• Interest to cancer genetics
Four main types of chromosomal aberrations
- Deletions
- Duplications
- Inversions
- Ring chromosomes
- Translocations (reciprocal or non-reciprocal)
- Chromosomal deletions
• A chromosome breaks in one or more places
• A chromosomal portion is lost
1. Terminal deletion
2. Intercalary deletion
• Also called Interstitial deletion
• Severity depends on size of deletion
What would be the outcome in the case of an acentric deletion?
the chromosome will be lost
acentric chromosome lack centromere hence hence the chromosome is lost during cell division/ mitotic division
Mitosis or meiosis with deletion chromosomes
- Partial chromosomes can’t pair properly
- Leads to the formation of a deletion loop (prone to breakage)
- Also known as a compensation loop
- Allows for synapsis to occur
50% normal chromosome
50% abnorml chromosone with deletion
Cri du Chat syndrome
- Partial deletion of chromosome 5
- 46, 5p-
- Partial monosomy
- Affected individuals tend to be:
- Anatomical deformities glottis & larynx
- Mental retardation
- Generally have normal life expectancy
Duplication
• Where a portion of a chromosome is duplicated
• Commonly produced as a result of:
1. Un-even crossing over
2. Errors in DNA replication
• High degree of phenotypic variation
• Not always a bad thing
Positive effects of duplication
- Gene redundancy
• Ribosomes are required in high numbers in metabolically active cells
• Having multiple copies of the rRNA gene allows for significant numbers to be
generated - Evolution
• Paralogous genes arose from a genetic duplication event
a new mutation in one of the gene = new gene
Negative effects of duplication
- MECP2 duplication syndrome
- Duplication of a region on X, q-arm
- X-linked inheritance (100% penetrant)
- Presents with
- Profound intellectual disability
- Hypotonia
- Predisposition to infections
- Epileptic seizures
- Inversions
Occurs when a chromosome breaks
at two points and re-joins
• 2 types:
1. Paracentric – centromere outside inverted
region
2. Pericentric – centromere inside inverted
region
• HINT: IC = includes centromere
Inversion arise from
Potentially arise from unusual looping of chromosome
- Genes are in balance – minimal effect on individual
- But can have consequences for offspring
- If the inversion interferes the expression of other genes (oncogenes)
Meiosis continues normally if the inversion is
homozygote for inversion
• Genes pair up during prophase
• Inversion will be passed onto
offspring
What happens when individuals are heterozygote for inversion?
Inversion loop forms if heterozygote
• Inversion loop forms to allow genes to pair during prophase (homologous pairing)
One normal chromosome and one with inversion
• If no cross-over occurs within inversion loop
• 50% will have inverted chromosome
• 50% will have a normal chromosome
Crossing over in pericentric inversion
Half normal gametes (one inverted,
but balanced)
Half abnormal gametes (carrying deletions) - duplicated /deteletd
Unbalanced - infertility
Crossing over in paracentric inversion
Gametes produced:
½ normal (normal and one inverted) ; ½ abnormal
Acentric fragment (no centromere)
get lost – cannot attach to spindle
Dicentric chromosome forms
dicentric bridge – fragment lost
Dicentric chromosomes
• Chromosome breaks during separation
• Fragment lost
• 2 normal gametes (1 with balanced
inversion)
• 2 deletion chromosomes – if fused
with normal gamete foetus not-viable
- Ring chromosomes
Form when breaks occur on both arms and the ends re-join
• Effects of ring chromosomes are severe
• Ring chromosome 14 syndrome
- Translocations
• Transfer of genetic material from one location to another
• Can occur within the same homologous pair
(intrachromosomal); or between non-homologous pairs
(interchromosomal)
• Reciprocal translocations – exchange of genetic material with replacement
• Non-reciprocal translocations - transfer of genetic material without replacement
Effects of translocations
- As long as the genetic material remains balanced – no consequence
- May affect meiosis
- Can disrupt important genes
- Interrupt important genetic regulatory sequences
Origins of translocations
- Chromosomal break & re-joining
- Abnormal crossing-over
Meiosis with chromosomes with translocations
• Similar to inversions, if the individual is homozygous for the
translocation – meiosis will continue normally
• If they’re a heterozygote, how do the chromosomes synapse?
• Form a translocation cross (quadrivalent)
Alternate segregation
Results in two normal gamate - 1 copy of normal chromosome 1 and one copy of normal chromosome 2
and Two balanced gamate = blanaced translocation
Adjacent one segregation
ALL 4 cell UNBALANCED translocation
ecah cell have chrosomome 1 and 2 kintochore
fusion of unbalaced gamate with a normal gamete results in unviable zygote
Robertsonian translocations
- Breaks can occur on the p-arms of acrocentric chromosomes
- Will reduce chromosome number by 2
- The p-arms are lost, and the two q-arms fuse
- Only tolerated if p-arms contain non-essential (redundant) genes
- Example: Familial Down Syndrome\
trivalent complex
Adjacent 2
rare
4 unbalanced gamate
Familial Down Syndrome
Normal
1 chromosome 14 and one 21 give rise to 4 gamates each with one chormatid 14 and 21
Accounts for about 3% of total Down Syndrome births
- Very common where parents give birth to multiple Down Syndrome children
- Robertsonian translocation between Chr 14 & 21
