Chromosomes and Chromosomal Abnormalities Flashcards
What are aneuploidies?
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes (whole extra or missing chromosome)
What are reciprocal translations?
Reciprocal translocations are a transfer of genetic material between homologous chromosomes. These are most commonly balanced exchanges, such that no genetic material is lost and individuals are phenotypically normal
What are Robertsonian Translocations?
• Two acrocentric chromosomes stuck end to end
In a reciprocal translocation, two different chromosomes have exchanged segments with each other. In a Robertsonian translocation, an entire chromosome attaches to another at the centromere
What are insertions and deletions?
Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. Deletions are mutations in which a section of DNA is lost, or deleted
What are duplications?
Duplication is a type of mutation that involves the production of one or more copies of a gene or region of a chromosome
What are inversions?
An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end to end. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself
(DEF -> FED)
How can we recognise different chromosomes?
- Banding pattern with specific stains
- Length
- Position of centromere
What are acrocentric chromosomes?
Acrocentric chromosomes have a centromere which is severely offset from the center leading to one very long and one very short section. (The short arm doesn’t really matter - satellite ribosomal genes, tRNAs etc)
What chromosomes are acrocentric?
Ch 13, 14, 15, 21 and 22.
What are the four different types of chromosome?
Metacentric
Submetacentric
Acrocentric
Telocentric
Name a chromosome change that causes disease
Unbalanced chromosome rearrangement
What is unbalanced chromosome rearrangement?
Balanced chromosome rearrangement
-All the chromosomal material is present
Unbalanced chromosome rearrangement
-Extra or missing chromosomal material. Usually 1 or 3 copies of some of the genome.
Having 1 or 3 copies of a part of your genome is developmentally bad news
What is nondisjunction?
When chromosomes fail to separate normally resulting in a gain or loss of chromosomes
What can nondisjunction result in?
Aneuploidy in cell lines
This is why nondisjunction birth defect rate increases with age
What happens in Trisomy of chromosome 21? (47 X-X/Y)
Down syndrome
What happens in trisomy of chromosome 18? (47 X-X/Y)
Edward syndrome
What is Edward syndrome?
Babies are often born small and have heart defects. Other features include a small head, small jaw, clenched fists with overlapping fingers, and severe intellectual disability
What happens in Trisomy of chromosome 13? (47 X-X/Y)
Patau syndrome
What is Patau syndrome?
The extra genetic material disrupts normal development, causing multiple and complex organ defects.
Approximately 90% of infants with Patau syndrome die within the first year of life.[8] Those children who do survive past 1 year of life are typically severely disabled with intellectual disability, seizures, and psychomotor issues
There’s a ton of symptoms associated w this
How may one get a rapid prenatal diagnosis for nondisjunction disorders?
Interphase chromosome counting using FISH (Fluorescence In Situ Hybridization)
What happens when a female has a missing X chromosome (Aneuploidy)?
Turner syndrome
What is Turner syndrome?
Caused by missing X chromosome in females
Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hairline at the back of the neck, short stature, and swollen hands and feet are seen at birth. Typically, they develop menstrual periods and breasts only with hormone treatment, and are unable to have children without reproductive technology.
What are the nondisjunction diseases associated with X chromosome aneuploidy?
45 X Turner syndrome
47 XXX Triple X
47 XXY Klinefelter syndrome
What is unique about conditions caused by X chromosome aneuploidy?
X Chromosome aneuploidy is better tolerated because of X inactivation
What are the major two chromosome mutations?
Chromosomal Insertion
Chromosomal Translocation
What impacts on foetal development does Robertsonian translocation?
Increased risk of trisomy in pregnancy
As chromosome 14 and 21 (two acrocentric chromosomes) may translocate onto one another which can result in an extra chromosome in the foetal cells
What are the possible results of Robertsonian translocation of acrocentric chromosomes 14 and 21 in pregnancy?
No translocation = normal
Balanced translocation = translocation occurs but does not result in extra genetic material (one combined 14-21 + 14 + 21)
Trisomy 14 = an extra Ch 14, results in miscarriage
Trisomy 21 = an extra Ch21, results in Down syndrome
What is the result of translocation of eccentric and centric fragments?
Dicentric chromosome and eccentric chromosome - not stable in mitosis
(One has two centromeres, one has none)*
What is the result of a reciprocal translocation of 2 eccentric fragments?
Stable reciprocal translocation
*Both have one centromere
What occurs when a chromosome 1 from the father that has undergone stable reciprocal translocation with a acentric fragment of chromosome 9 combines with an unaltered maternal chromosome 9?
Partial:
Trisomy 9
Monosomy 1
What are the reproductive risks of reciprocal translocations?
• for most translocations, ~50% of conceptions will have either normal chromosomes or the balanced translocation
• unbalanced products result in–
– miscarriage (large segments)
– dysmorphic delayed child (small segments)
What is the Philadelphia chromosome?
An abnormally small chromosome 22 as a result of uneven reciprocal translocation of genetic material
Specifically found in leukaemia cancer cells (particularly chronic myeloid leukaemia (CML) cells)
95% of CML patients have Ph Ch
What are the single chromosome mutations?
Deletion
Duplication
Inversion
What is X-linked Ichthyosis a result of?
Chromosomal deletion
What is Charcot Marie Tooth Disease a result of?
Chromosomal Duplication
What is Charcot Marie Tooth Disease?
- Damage to myelin sheath in peripheral nerves- progressive loss of muscle tissue and touch sensation
- Mutations in 39 genes can cause CMT
- Commonest form- CMT1A- 70- 80% cases have large duplication of 17p11.2
