Chromosomes and Chromosomal Abnormalities Flashcards
Identify the main parts of a chromosome.
Telomere Short arm (p) Centromere Long arm (q) Telomere
How are different chromosomes recognized in a karyotype ?
- Banding pattern with specific stains
- Length
- Position of centromere
How are the short and long arm of a chromosome denoted ?
Short arm denoted p
Long arm denoted q
Which of the human chromosomes is the largest ? smallest ?
Ch 1 is largest
Ch 22 is smallest
Define Acrocentric Chromosomes.
A chromosome in which the centromere is located quite near one end of the chromosome (The short arm doesn’t really matter)
Identify the human acrocentric chromosomes.
Ch 13, 14, 15, 21 and 22
Identify the main parts of an acrocentric chromosome.
Satellite ribosomal genes, tRNAs etc.
Centromere
Long arm
Identify and briefly define the main balanced and unbalanced chromosome rearrangements that cause disease.
1. Balanced chromosome rearrangement: All the chromosomal material is present (person likely to have normal phenotype). This may be due to: -Inversions -Translocation
2. Unbalanced chromosome rearrangement Extra or missing chromosomal material. Usually 1 or 3 copies of some of the genome (more likely to induce abnormal phenotype) This may be due to: -Aneuploidy -Insertions -Deletions -Duplications
Identify conditions associated with aneuploidies.
Trisomy 21- Down syndrome Trisomy 18 - Edward Syndrome Trisomy 13 –Patau syndrome Turner syndrome (45 X ) Triple X (XXX) Klinefelter syndrome (XXY)
Describe methods used to diagnose aneuploidies prior to birth.
FLUORESCENCE IN SITU HYBRIDIZATION (FISH)
- Interphase chromosome counting in sample of amniocentesis
- DNA probe designed to latch on particular chromosome. Should normally get lighting up twice in cells of the sample (because 2 chromosomes normally) but in cells of trisomic embryos, lightening up three times
ARRAY CGH (more common and quicker than FISH)
- Take patient and normal DNA, label them different colors, mix them together.
- Array covered in probes that the DNA will attach to.
- If equal amounts of patient and control DNA, they compete for the probes and get equal attachment (=equal hybridization)
- If patient has something missing or something extra, imbalance in how much of patient and how much of control attach to microarray
- Computer generates a plot to show this
Why is X Chromosome aneuploidy better tolerated than autosomal aneuploidy ?
Because of X inactivation (in the case of XXX and XXY, will inactivate most of X anyway)
Identify the major two chromosome mutations.
Insertions and translocations
Describe chromosomal insertions.
- Bit of chromosome get stuck inside other chromosome
- One ends up shorter, other ends up longer
- Still got all your genetic information, just not in the right place
- Phenotypic abnormalities depends on where break points
Identify and describe the types of translocations.
- ROBERTSONIAN TRANSLOCATIONS
- Two acrocentric chromosomes stuck end to end
- Very likely to be phenotypically normal (break points will not be at bad points)
- Increased risk of trisomy in a pregnancy - RECIPROCAL TRANSLOCATIONS
- Fragmentation results in 2 acentric fragments (with no centromeres) and 2 centric fragments
- Possibility 1: Exchange of acentric and centric fragments, resulting in dicentric and acentric chromosomes (not stable in mitosis)
- Possibility 2: Exchange of 2 acentric fragments, resulting in stable RECIPROCAL TRANSLOCATIOn
Identify the possible outcomes with a normal father and mother who has a Robertsonian Translocation (14, 21)
- Normal (if each parent pass on their normal chromosomes)
- Balanced Translocation (Mom passes on her translocation as chromosome 14 but no other chromosome)
- Trisomy 14 (Miscarriage, mom passes on one normal chromosome and other one is the one carrying translocation)
- Trisomy 21 (Mom passes on one normal chromosome and other one is carrying translocation. Risk to next offspring of having Down Syndrome if prior child gets this kind of Trisomy 21)
Identify the possible outcomes with a normal father and mother who has a reciprocal Translocation (1, 9).
- Normal (if each parent pass on their normal chromosomes)
- Balanced 1,9 Translocation (if father gives normal chromosomes and parent 2 gives 2 reciprocally translocated chromosomes)
- Partial Trisomy 9 + Monosomy 1 (if father gives normal chromosomes and parent 2 gives 1 reciprocally translocated chromosome 1 with a bit of 9 in it and one normal chromosome)
- Partial Trisomy 1 + Monosomy 9 (if father gives normal chromosomes and parent 2 gives 1 reciprocally translocated chromosome 9 with a bit of 1 in it and one normal chromosome)
Describe what the following means:
Mother: 46,XX,t(12;17)(p13;p13)
Mother with 46 chromosomes, including a translocation between chromosome 12 and 17 (13 is the part of the short arm of each chromosome which was swapped over)
Describe what the following means:
Son: 46,XY,der(17)t(12;17)(p13;p13)mat
Son has 46 chromosomes, with a derived chromosome 17 due to a translocation between chromosomes 12 and 17 (13 is the part of the short arm of each chromosome which was swapped over). This probably caused partial trisomy 12.
Describe Philadelphia Chromosomes.
- Changed chromosome 22 as a result of reciprocal translocation with chromosome 9
- Results in longer chromosome 9 and shorter chromosome 22
- Abl gene on chromosome 9
- Bcr gene on chromosome 22
- Bcr-abl fusion gene as a result of translocation
- Bcr-abl is a chimeric oncogene
What proportion of CML patients have Philly ch ?
95%
Identify the single chromosome mutations.
- Deletion
- Inversion
- Duplication
Identify a condition associated with chromosomal deletion.
X-linked Ichthyosis
-Skin condition
Identify a condition associated with chromosomal duplication.
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 but most cases due to chromosomal duplication of 17p11.2
Identify a condition associated with chromosomal inversion.
Mainly not associated with abnormal phenotypes (unless break points go through middle of gene, which they usually do not)
What are the reproductive risks for people with reciprocal translocations mutations
Trisomy 21 - Down Syndrome
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Trisomy 18 - Edward Syndrome
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Trisomy 13 - Patau Syndrome
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