Lecture 7 & 8 Flashcards
What is more stable DNA or RNA?
DNA is more stable as the OH group in ribose can attack the phosphate bond making RNA much more transient
Which direction is DNA synthesised in?
5’ to 3’. It is the antisense strand that is copied
What are chromosomes
Chromosomes are lined double stranded DNA molecules
Human DNA Statistics
3000M BP, 20000 coding genes approx 50-100MB, mRNA reduced to 2 MB due to spicing
Name the types of Sequence classes in DNA
1) Single copy sequence - most protein coding genes
2) Repetitive sequences
a) Interspersed e.g. Alu repeats
b) Satellite - e.g. haemochromatin –> large blocks of repetitive DNA
What is alternative splicing
Eons spliced together in different combinations to create alternative proteins, takes the diversity of the genome above 20000
What are pseudogenes
When genes accumulate mutations hence are inactivated and no longer work –> may be similar DNA to functioning genes and can interrupt with medical diagnosis
What is a processed gene
An intron-less copy of another gene found somewhere else in the genome not usually near the parent gene.
Occurs when mRNA is reverse transcript and reintegrated into the gene e.g. retroviruses. Occasionally genes still function but many are pseudogenes
Satellite DNA
Large blocks at centromeres and heterochromatic regions They are simple tandem repeats e.g. alphoid DNA at centres
Variable in size due to polymorphisms
What is alphoid DNA
171bp repeat sequence at the centromeres and specific to chromosomes –> allows identification
Essential for assemnly of the controllers
Alu Repeats
there are 500000 copies scattered within the genome, interspersed repeat. Dispersed due to retrotransposition and reintegration. Role in molecular pathology
How do interspersed repeats cause problems
Chromosomes misalign in meiosis 1. Can cause Inrame deletion or out of frame
Deletion/Insertion mutations
Variable effects. PCR May miss if heterozygous as still have 1 normal copy of the gene
What is Duchenne
Deletion mutations
What type of mutation is Charcol - Marie Tooth
Duplication mutations
What type of mutation is haemophilia
Gross rearrangement
Describe Haemophilia Mutations
X linked Recessive (Xq28).
Homologous region of F8C gene further down, this section is inverted and inserted between the real F8C –> as a result F8C gene is chopped in half and doesn’t work
Hard to detect in PCR as all eons are still present
Point Mutation Description
May be silent or missense (Conservative or non-conservative)
Where does hyper mutability occur?
At CpG nucleotides –> as cytosine can be methylated, methyl cytosine can then be deaminated to thymine causing a CG-TG mutation which accounts for 1/3 of all mutations
Describe nonsense mutations
substitutions, often produces stop codons causing truncated protines
Frame shift mutations
Alters protein beyond the mutations, may truncate protein, commonly underlie genetic diseases
What codes for a splice junctions
GT:AG –> mutations can change splice sites potentially leaving introns in the mRNA
What is compound heterozygote?
has 2 recessive alleles for the same gene but alleys may be different to each other (i.e. mutated in a different place)
Mutations heterogeneity is frequent or infrequent?
Frequent, where different mutations cause the same disease i.e. Cystic fibrosis and Beta thalassaemia
Describe Hardy Weinberg Equation
p = mutant allele, q = normal allele (1-p) carrier = 2pq
What does dominant inheritance sometimes cause
Results from a mutation causing a gain or alteration rather than a loss of function. It has a smaller mutational spectrum and new mutations are comparatively cmmon
Achrondroplasia descrive
Dominant mutations. Glycine to Arginine mutations
Name the 3 types of trinucleotide repeat expansions (where 3 amino acids are repeated)
1) polyglutamine repeates
2) Large non-coding repeated
3) MUtational instability
1) Polyglutamine repeats describe
CAG repeats involved in neurodegenerative disorders i.e. Huntingtons and Spinocereballar ataxia. Triplet repeats in the coding region
1) Large non-coding repeats
Not in coding region
Fragile X syndome –> transcriptional silencing and Myotonic dystrophy
Mutation Instability
Occasional Huntingtons (7-9 is normal repeats, over 30 is disease) Frequently occurs in Fragile X where there is variability in trinucloetide repeats. Variability is normal but higher repeats cause damage
Describe Fragile X syndrome
CGG repeat expansion in non-coding repeats. Normal repeats are 5-50, unstable is 50-200, full mutation is over 200. If a mother has an unstable X then this leads to the full mutation in the son
What is morphology
the study of the structure and form of animals and plants
When is a malformation more likely to be genetic
if the mutation is multiple, dysmorphic and there is a familyy history
Deep plantar creases associated with what trisomy
trisomy 8
Are spina bifida and cleft lip isolated or genetic
Spina bifida is isolated, cleft lip is isolated but sometimes genetic
22q11.2 Deletion
Degeorge Syndrome
Learning difficulties, cleft palate, velopharyngeal insufficiency, congenital heart disease, hypocalcaemia, seizures, immune defeciency, renal malformation
Describe achondroplasia
Autosomal dominant –> often a mutation. Increased risk with increased paternal age! limb shortening, short stature, foramen magnum compression/hydrocephalus
Beckwith-widemann syndrome
Large tongue, ear pits/creases, exomphalos, hemihypertrophy, neonatal hypoglycaemia
INCREASED RISK OF WILMS TIMOUR (nephroblastoma)
Down syndrome - the commonest chromosomal disorder
Learning difficulties, congenital heart disease, hypotonia in neonates, single palmar crease (but 4% of normal population have unilateral and 1% bilateral), cataracts, hearing problems, hypothyroidism, leukaemia, atlanta-axial instability, Alzheimers
Kabuki Syndrome
learning difficulties, congenital heart diseases, poor growth, hearing impairment, cleft palate, premature breast development, persistent metal finger pads (96%) and eversion of lateral 1/3 of eyelid
Mosaicism
Can cause hypo or hyper pigmented skin patches, may follow Blanschkos lines and diagnosis often requires skin biopsy
Pseutz-Jeghers Sundrome
Gastrointestinal polyps can cause bleeding and obstructions
Malignancies –> colorectal, gastric, pancreatic, breast and ovarian
Treacher Collins Syndrome
Autosomal dominant. Vary variable cleft lip and hearing impairment,
Waardenburg syndrome
Sensorineural hearing impairment, iris heterochromia, premature greying, white forelock, areas of skin hypo pigmentation, congenital malformations (hirschsprungs/USD)
Williams Syndrome
7q11 deletion
Learning difficulties, cocktail party speech, congenital heart diseases (supravalvular arctic stenosis and peripheral pulmonary artery stenosis). Hypercalcaemia)
