Genetics Flashcards
What is penetrance
the proportion of people with a particular genetic change who exhibit symptoms of a genetic disorder
What is reduced/incomplete penetrance?
Give an example.
when some people with a particular mutation do not develop features of a disorder
for example some people with the BRCA1 or BRCA2 mutation will develop breast cancer and others will not
What is aged-related penetrance?
Give an example.
a delay in the onset of a genetic disease
for example Huntington’s is autosomal dominant - only 50% of people with the mutation have developed signs by age 50
BRCA1 and breast cancer is another example. Incidence increases with age as breast cells need “two hits” (one on top of the mutation)
What is anticipation?
Give an example of a genetic disease which shows this.
in successive generations of people with a given mutation age of disease onset is reduced and phenotype is more severe - may correlate with no. of triplet repeats
for example CAG repeats in Huntingtons
What is a chromosome
a single molecule of DNA
What is a gene
a DNA sequence containing instructions for a protein/RNA
What technique can be used to visualise chromosomes
light microscopy
How many pairs of chromosome, autosomes and sex chromosomes does a healthy person have?
23 pairs of chromosomes
22 pairs of autosomes
1 pair of sex chromosomes
A few techniques that can be used to examine chromosomes
FISH
Array CGH
What is mosaicism
when a person has 2 or more genetically different sets of cells in his or her body, usually due to an error in mitosis
eg in Downs syndrome (trisomy 21) 1% of people have mosaicism so some of their cells have 3x chromosome 21 whereas some of their cells have the (normal) 2x chromosome 21
What is the gene dosage effect hypothesis
having an increased or decreased amount of specific gene products causes the features of the syndrome
eg in Downs syndrome having 1.5x the products of ch.21
Aneuploidy =
a chromosomal mutation in which there is one or more extra chromosomes, or one or more fewer chromosomes.
Polyploidy =
a chromosomal mutation in which a cell has entire extra sets of chromosomes.
What is non-disjunction in meiosis
this is what leads to aneuploidy
Where at least one pair of homologous chromosomes do not separate. The end result is a cell/cells with an extra copy of a chromosome and a cell/cells missing that chromosome
Why is aneuploidy (1 or more extra/missing chromosomes) associated with mothers of increased maternal age?
Oocytes have been arrested in prophase I of meiosis since the mother was 6months inside the womb. They may not complete MI (when they are ovulated) for 50 years.
All this time sitting around - they accumulate wear and tear which may effect spindle formation or their repair mechanisms pre-disposing them to non-disjunction
Triploidy =
3 copies of all the chromosomes (69, XXX/XXY/XYY)
What is a robertsonian translocation
Breakage of two acrocentric chromosomes (13, 14, 15, 21, 22) at or close to their centromeres.
Subsequent fusion of their long arms - short arms are lost.
(no arm breakage as with reciprocal translocation, whole chromosomes join end to end)
What is a reciprocal translocation
Breakage of the arms of two non-homologous chromosomes with exchange of the fragments (‘balanced’).
Any chromosome can be involved in a reciprocal translocation.
what are chromosomal deletions and duplications due to
unequal crossing-over during meiosis, usually in a region of repeats
A dominant mutation is likely to half the concentration of which type of gene product?
structural protein or receptor
A recessive mutation is likely to half the concentration of which type of gene product?
an enzyme
Why do some females show X-linked recessive traits?
Skewed X inactivation - one X favoured for inactivation over the other
Homozygous for recessive allele - eg colour blindness
Turner syndrome - missing an X
X inactivation in females: Why does it happen? When does it happen? Which X is inactivated? How is it inactivated?
- X inactivation happens so females do not get a double dose of X active genes compared to males.
- X inactivation occurs in the blastocyst…
- …via epigenetic changes to 1 X chromosome - DNA methylation - which turns it into inaccessible, condensed chromatin (a “Barr body”)
- Which X is inactivated is totally random in every cell!
What is a tell-tale characteristic of X-linked inheritance
no male to male transmission of the disease
