Chromosomal disorders Flashcards
What is cytogenetics?
The study of inheritance and structure of chromosomes
What is karyotoping?
A karyotope is a photograph of someones chromosomes that allows scientists to determine whether someone has the correct number of chromosomes (22 pairs of autosomes and 1 pair of sex chromosomes - 46 chromosomes all together) and whether they are all structurally correct. Hence a karyotope will only detect gross changes not small changes like point mutations or deletions.
What would a abnormal genetic finding from the laboratory labelled 9p34 indicate?
There is an abnormality on chromosome #9 at loci 34 of the p arm of the chromosome. The p arm is the shorter arm towards the top of the chromosome.
How common are numerical abnormailites?
Not very common - most pregnancies with additions or deletions of whole chromosomes are not viable with life and hence are spontaneously aborted.
What is aneuploidy?
What is monosomy and what is trisomy?
How is aneuploidy most likely to arise?
A mechanism of a numerical chromosome abnormailty where there is a gain or loss of a whole chromosome.
Loss of one chromosome = monsomy
Gain of one chromosome = trisomy
Aneuploidy is most likely to arise from non disjunction at meiosis 1 or meisosi 2.
What is mosaicism?
Mosaicism occurs post zygotically (after fertilisation) and is a condition in which different cells in the same individual have different numbers or arrangements of chromosomes.
Often the individual will show the same phenotype/condition as someone else with the same chromosome abnormality but non-mosaicly. Because however only some of their cells are affected this can mean that sometimes the condition is less severe.
What is one of the most common viable examples of aneuploidy?
Downs syndrome - trisomy 21 (three copies of chromosome 21)
It is associated with increased maternal age and is characterized by mental retardation, facial features and other organ abnormalities.
What are some of the aneuploidy conditions of sex chromosomes?
Klinefelter syndrome
- two or more X chromosomes in a male (XXY).
- this results in typically smaller testes that do not produce as much testosterone as usual and because testosterone is important in directing male sex development, puberty is often delayed
Turner syndrome
- only one X chromosome in a female (X)
- this results in short stature and usually infertility. Most women will require hormone therapy in order to go through puberty.
XYY syndrome
- causes extremely tall mean but most other physical features are normal and they are able to have children
What are the four main structural abnormalities that can occur with chromosomes?
Reciprocal translocation
Robertsonian translocation
Inversion
Deletion
What is a reciprocal translocation and what effect does it produce?
A reciprocal translocation is where there is exchange of DNA material between two non homologous chromosomes. eg a section of chromosome 3 is swapped with a segment of chromosome 11. If this is balanced (no DNA is lost of gained) then the phenotype is normal.
What is a robertsonian translocation and what effect does it produce?
A robertsonian translocation is where two homolgous or non homolgous acrocentric chromosomes fuse to form one chromosome so you end up with 46 chromosomes. This is responsible for a small percentage of downs syndrome.
What are acrocentric chromosomes?
Chromosomes that have their centromere located very closely to one end of the chromosome so the short arm is very small. We have 5 in the human genome.
What is inversion and what effect does it produce?
Inversion occurs when a chromosome has two breaks in it and a segment then breaks away, rotates 180 degrees and then re-inserts into the chromosome so now the top bit if the segment is at the bottom.
This can be pericentric = break involves both arms of the chromosome and the centromere
or Paracentric = break only involves one arm of the chromosome
Inversions dont typically result in phenotypic abnormalities.
What is deletion and what effect does it produce?
Deletion occurs when there is one break near the end of the chromosome so the terminal piece breaks off (terminal deletion) or when there are two breaks in a chromosome so a segment within the chromosome breaks off (interstitial deletion).
Unlike the other forms of structural chromosome abnormailities, this results in the loss of DNA and hence there will always be some kind of functional or phenotypical abnormality.
What is FISH?
FISH = fluorescent in situ hybridisation
It is a method used by researchers that can be performed on pretty much any cell (dividng or non dividing) to identify where certain regions of a gene are within a chromosome.
.The first step is to generate a probe - prepare short sequences of single-stranded DNA that match a portion of the gene the researcher is looking for and label it with a radioactive dye.
DNA is composed of two strands of complementary molecules that bind to each other like chemical magnets. Since the researchers’ probes are single-stranded, they are able to bind to the complementary strand of DNA, wherever it may reside on a person’s chromosomes. When a probe binds to a chromosome, its fluorescent tag provides a way for researchers to see its location.
