MCD- Genetics (1,2,6&7) Flashcards
What are congenital abnormalities¬ and what are the contributions of genetic factors to these abnormalities?
Congenital abnormalities are conditions present at birth. Genetic factors contribute to 40% of all congenital abnormalities.
What is a malformation?
This is an error of morphology (shape/structure) of an organ. A primary structural defect, where something goes wrong at a very early stage and cannot be fixed.
What is a disruption?
This is where the embryo begins developing normally and an environmental factor causes an abnormal result.
What is a deformation?
The abnormal form, shape or position of a part of the body caused by mechanical forces (such as a club foot due to lack of space in the womb). These abnormal forms can be treated with surgery.
What is a dysplasia?
An abnormal organisation of cells into tissues and the morphological results.
What is a sequence?
A pattern of multiple anomalies derived from a single known prior anomaly or mechanical factor. Eg. The potter sequence is where there is a failure to produce urine resulting in ogliohydramnios, potter faces, and clubbed feet.
What is a syndrome?
Multiple anomalies thought to have a common cause and not representing a sequence. Eg. Down syndrome
What is an association?
A condition where there are multiple abnormalities where the reason why is unknown. An example is VATERL.
Describe the levels of organisation in the nucleus
DNA makes genes, which are wrapped around histones to form nucleosomes. Nucleosomes form 30nm fibres which condense to form chromosomes which then form the genome.
What are the long and short arms of the chromosome labelled as? How are they numbered?
The short arm is p, while the long arm is q. The arms are numbered out from the centromere.
Describe the different types of structural abnormalities
A structural abnormality includes duplication, where the genetic material is repeated, inversion, where it is swapped around, deletion, where some of the gene is removed, and ring, where the ends of the chromosome fuse together to form a ring.
What is a Robertsonian translocation? Does it cause an abnormal phenotype?
Robertsonian translocations are where the chromosomes break at their centromeres and the q arms dude to form a single chromosome. This can have no effect as the same genetic material is present - unless a gene is disrupted or gene fusion occurs.
Define aneuploidy and summarise the 3 types of aneuploidy.
Aneuploidy is an abnormal number of chromosomes in the cell:
- Monosomy is the loss of a chromosome, which is almost always lethal.
- Trisomy is the gain of 1 chromosome, such as at chromosome 21 in Down syndrome.
- Tetrasomy is the gain of 2 chromosomes, which can be tolerated for some chromosomes.
Describe the effects and features of trisomy 21.
- Newborns have excess nuchal skin, lethargy and hypotonia (decreased muscle tone)
- Craniofacial features include small ears, brushfield spots (white spots in the iris) and macroglossia (an unusually large tongue)
- Limbs - wide gap between first and second toes.
- Cardiac issues - Patients have a short stature, and duodenal atresia (absence of closure of a portion of the lumen in the duodenum, causing increased amniotic fluid during pregnancy)
What happens in trisomy 21 during meiosis?
There is non-disjunction in meiosis I or II, resulting in an extra chromosome. There can also be a Robertsonian translocation, which can be carried by parents and increases the risk of further Down syndrome babies. A carrier of t(21;21) has a 100% chance of a Down syndrome baby, as any other fetuses will not survive. De novo translocations can also occur in the child.
What is mosaicism?
During division in the zygote non dysjunction occurs, forming some cells with trisomy and some with monosomy. This is more serious early on as it will affect the patient more.
Why do trisomies cause disease?
There will be overexpression of some genes disrupting cell function, for example producing more transcription factors than necessary.
What is turners syndrome?
This is where there is monosomy X, only one X chromosome is present in a female, resulting in a webbed neck, low set ears, low hairline, broad chest, and aortic defects. Treatment requires growth hormones or oestrogen. Can be due to a ring chromosome.
What is Klinefelter syndrome?
XXY where a patient is phenotypically male, causing infertility, patients are taller than average, and patients have learning disabilities.
What is dosage compensation?
Random inactivation if a single X chromosome in females, ensuring equal gene expression in all sexes. This results in daughter cells having the same inactive chromosome - seen in tortoiseshell cats.
How is it possible to be chromosomally one gender and phenotypically the other?
The SRY gene on the Y chromosome may have translocated to an X chromosome in females, resulting in a male. Or, the SRY gene in a male could be deleted resulting in an infertile female (phenotypically).
What happens to risk of trisomy 21 as maternal and paternal age increases?
Increase in maternal age results in increased Down syndrome risk - increase in paternal age has no increased risk.
What is copy number variation?
This is where a section of a gene is repeated, for example in Huntington’s disorder the CAG in a gene is repeated. The number of repeats increases through generations, and therefore so does the severity and the onset of the disease will become earlier.
List the 3 chromosome aberrations that lead to Downs syndrome
- Trisomy 21
- De novo translocations
- Parents are carriers of translocations
What is the difference between a monogenic and complex disorder?
A monogenic disorder has clear inheritance, and is individually rare, while a complex disorder is affected by the environment, and is usually more common.
What is the difference between a mutation and a polymorphism?
Mutations are a inheritable change in DNA sequence. A polymorphism is a mutation that is present in over 1% of the population. If a monogenic disease is caused, it is referred to as a mutation.
