Chromosomes and Chromosomal Abnormalities - Genetics 2 Flashcards
How is a chromosome recognised?
- Banding pattern with specific stains
- Length
- Position of the centromere
What can the short arm of the chromosome be written as?
p
What can the long arm of the chromosome be written as?
q
What is an afrocentric chromosome?
- Doesn’t really have a short arm (little bit that encodes satellite ribosomal genes, tRNAs etc)
- Has a centromere and a long arm
- Only chromosomes 13, 14, 15, 21 and 22
What is a balanced chromosomal rearrangement?
• All chromosomal material is present
What is an unbalanced chromosomal rearrangement?
- Extra or missing chromosomal material, usually one or three copies of the same gene
- Developmentally ‘bad news’
What is aneuploidy
When there is a whole extra or missing chromosome
What is Translocation?
Rearrangement of chromosomes
What is Aneuploidy usually caused by?
Nondisjunction in meiosis in either meiosis 1 (resulting in two gametes having 3 chromosomes and two having one) or in meiosis 2 (resulting in two gametes being normal and one having 3 and the final having only one)
What is Down syndrome?
Trisomy 21 (3 copies of chromosome 21)
What is Edward syndrome?
Trisomy 18
What is Patau syndrome?
Trisomy 13
How can chromosomal defects be tested before birth?
- Interphase chromosome counting using FISH (fluorescence In situ Hybridization)
- Chromosome will fluoresce and then can be counted, for example: a trisomy will show 3 fluorescent chromosomes instead of 2
How can chromosomal defects be tested (not before birth)
Array CGH (comparative genome hybridisation)
• Patient DNA and Control DNA of an equal amount and normal chromosome complement are mixed
• Hybridise them into a gene chip and if the control DNA and the patients DNA match, it should produce an even graph with equal amounts of the control and patient DNa
• If there is less or more of the patient DNA/chromosome this will be shown as a slight dip or a peak in the graph
What is Turner syndrome?
45X: only one sex chromosome
Why is X chromosome aneuploidy better tolerated?
Because of X inactivation
What are the X chromosome aneuploidies?
- Turner syndrome: 45 X
- Triple X: 47 XXX
- Klinefelter syndrome 47 XXY (male)
What is chromosomal insertion?
- Area of one chromosome is inserted into another
- Usually not known or recognised until they go on to have children (as long as the insertion doesn’t cut through a gene)
What is Robertsonian translocation?
- Only affect the acrocentric chromosomes (13, 14, 15, 21 and 22)
- 2 Acrocentric chromosomes get stuck end to end
- An example would be 45 XY t(14:21)
- Prior to testing they may not be aware of this translocation
What are the different chromosomal results for the children of a mother with a roberstonian translocation (45 XX t(14:21) and a father with normal chromosomes
- Normal - inherits the normal versions of each gene from both parents
- Balanced translocation - inherits the normal versions from the father and the translocated version from the mother: 45XX/XY t(14:21)
- Trisomy 14 - inherits the normal versions from the father and one normal 14 from the mother and the translocated chromosome (results in miscarriage)
- Trisomy 21 (Down syndrome) - inherits the normal version from the father and the translocated chromosome and a normal 21 chromosome
How can the chromosomal pattern for someone with Down syndrome that has been caused by an inherited Roberstonian translocation be written (boy)?
46 XY der(14:21) + 21
What is a reciprocal translocation?
- Can happen with any of the autosomes
- Exchange of 2 eccentric fragments of a chromosome (stable)
- Exchange of eccentric and centric fragments- dicentric and not stable in mitosis
What are the different chromosomal results for the children of a mother with normal chromosomes (1 and 9) and a father with one set of reciprocal translocated chromosomes (one normal 1, one normal 9, one pair of reciprocally translocated 1 and 9)?
- Normal - inherit normal chromosomes from both parents
- Balanced 1;9 translocation - normal set from mother, both reciprocally translocated chromosomes from father
- Partial Trisomy 9 and monosomy 1 - normal from mother, one reciprocally translocated from father and one normal chromosome 9
- Partial Trisomy 1 and monosomy 9 - normal set from the mother, one translocated chromosome from father and one normal chromosome 1
If a mothers chromosomal pattern is written as 46, XX, t(12:17) (p13;p13), what is the sones if he has inherited the translocation?
46, XY, der(17) t(12;17) (p13;p13)mat
What are the reproductive risks of reciprocal translocations?
- 50% chance no effect: either balanced translocation or normal
- 50% unbalanced: if large segment, miscarriage and if a small segment, dysmorphic delayed child
What is a Philadelphia chromosome?
- Reciprocal translocation between Ch 9 and Ch 22
- Forms a bcr-abl gene (an oncogene)
- 46, XY, t(9:22) (q34;q11.2)
- 95% of patients with chronic myeloid leukaemia (CML) have this gene
What is the Charcot Marie Tooth Disease?
- Duplication (happens in 39 genes, 70-80% of the time on Ch 17 on p)
- Results in damage to the myelin sheath
