mutations + genetics Flashcards
nucleolus
Site of transcription and assembly of rRNA
chromatin
mixture of DNA, proteins and RNA that package DNA within the nucleus.
It is divided between 2 forms
heterochromatin (condensed) - transcriptionally inactive
euchromatin (extended) - transcriptionally active
mechanisms by which chromatin is made more accessible
Histones can be
- enzymatically modified
- displaced by chromatin remodeling complexes
- These processes are reversible
DNA Replication
semi-conservative
i.e. one-half is old; one-half is new.
bi-directional
i.e. replication in two directions
(leading & lagging strand)
DNA replication steps
(usage of DNA polymerase)
[1] Proteins unzip the double helix by breaking the hydrogen bonds
[2] New nucleotide molecules are then paired with the two DNA strands.
Leading strand:
Synthesizes DNA in a 5’ to 3’ brine direction in one go
Lagging strand:
Synthesizes DNA in 5’ to 3’ brine direction using a series of short fragments [Okazaki fragments]
Stiched together by DNA ligase once completed
Uses RNA primer in between the series
alternative splicing
exons of the RNA produced by transcription of a gene (a primary gene transcript or pre-mRNA) are reconnected.
The resulting different mRNAs may be translated into different protein isoforms;
thus, a single gene may code for multiple proteins.
tRNA and rRNA
tRNA - acts as an adapter molecule between the coded amino acid and the mRNA.
-role is to translate mRNA sequence into amino acid sequence.
rRNA - combines with proteins to form a ribosome
- Produced in the nucleus & transport to cytoplasm
sickle cell anaemia
an inherited blood disorder
a single nucleotide substitution leads to a pathological phenotype by changing the expressed amino acid thus changing the structure of the protein.
Adenine to Thymine substitution leads to → encoding changes from Hydrophilic Glutamate to Hydrophobic Valine
chromosome abnormalities
Numerical
→ wrong number of chromosomes in a karyotype
Structural
→ large scale rearrangement of chromosomes in a karyotype
Mutational
→ small scale changes from deletions to base pair changes
mutation terminology
Monosomy - the state of having a single copy of a chromosome pair instead of the usual two copies
Trisomy - a chromosomal condition characterised by an additional chromosome.
→ 47 chromosomes instead of 46
→ related to first trimester miscarriages
Triploidy - a condition in which there are three complete sets of chromosomes in a single cell
→ 69 chromosomes
Tetraploidy - a condition in which there are four complete sets of chromosomes in a single cell.
→ 92 chromosomes
Why does down syndrome incidence go up with increasing maternal age?
Because of increases in nondisjunction during meiosis
→ egg cells sitting in meiosis I for decades…
nondisjunction
failure of homologous chromosomes or sister chromatids to separate properly during cell division.
autosomal and sex chromosome aneuploidy syndromes
autosomal
down syndrome
patau syndrome
edwards syndrome
sex chromosome
turner syndrome
klinefelter syndrome
downs syndrome
Trisomy 21
– Incidence: 1 in 700
* Increases with advancing maternal age
– Characteristic facial dysmorphologies
– IQ less than 50
– Average life expectancy (50-60 years)
– Alzheimer’s disease in later life
– Chromosomal findings
* Trisomy 21: non-disjunction (95%), usually maternal origin
* Unbalanced Robertsonian translocation (4%)
* Mosaicism (1%)
patau syndrome
Trisomy 13
– Incidence: 1 in 5000
– Multiple dysmorphic features and mental retardation
– About 5% die within first month, very few survive beyond first year
– Non-dysjunction (90%), maternal origin
– Unbalanced Robertsonian translocation (10%)
edwards syndrome
Trisomy 13
– Incidence: 1 in 5000
– Multiple dysmorphic features and mental retardation
– About 5% die within first month, very few survive beyond first year
– Non-dysjunction (90%), maternal origin
– Unbalanced Robertsonian translocation (10%)
turner syndrome
45,X
– Incidence: 1 in 5000 to 1 in 10000 (liveborn)
– Incidence at conception much greater, about 97% result in spontaneous loss
– Females of short stature and infertile
– Neck webbing and widely spaced nipples
– Intelligence and lifespan is normal
klinefelter syndrome
47,XXY
– Incidence: 1 in 1000
– Tall stature, long limbs
– Male but infertile, small testes, about 50% gynaecomastia
– Mild learning difficulties
structural abnormalities
characterized by gross large scale rearrangement in the karyotype.
Balanced or unbalanced rearrangements
Can occur through:
Translocations
– Reciprocal: involving breaks in two chromosomes with formation of two new derivative chromosomes
– Robertsonian: fusion of two acrocentric chromosomes
Deletions - a part of a chromosome is left out during DNA replication
Insertions
Inversions - a chromosome rearrangement occurs in which a segment of a chromosome is reversed end to end.
balance translocation
when the same amount and number of copies of the original DNA are still present after a part of a chromosome has broken off and reattached in another location.
i.e. there is no DNA missing or additional DNA
unbalanced translocation
when a different amount and number of copies of the original DNA are present after a part of a chromosome has broken off and reattached in another location.
i.e. there is DNA missing or additional DNA
genetic mutation
Germline or
gene disruption
Somatic
disease-associated
Polymorphism
– No phenotypic effect
– Frequency >1%
