Lecture 7 & 8

Question 1

What is more stable DNA or RNA?

Answer 1

DNA is more stable as the OH group in ribose can attack the phosphate bond making RNA much more transient

Question 2

Which direction is DNA synthesised in?

Answer 2

5’ to 3’. It is the antisense strand that is copied

Question 3

What are chromosomes

Answer 3

Chromosomes are lined double stranded DNA molecules

Question 4

Human DNA Statistics

Answer 4

3000M BP, 20000 coding genes approx 50-100MB, mRNA reduced to 2 MB due to spicing

Question 5

Name the types of Sequence classes in DNA

Answer 5

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

Question 6

What is alternative splicing

Answer 6

Eons spliced together in different combinations to create alternative proteins, takes the diversity of the genome above 20000

Question 7

What are pseudogenes

Answer 7

When genes accumulate mutations hence are inactivated and no longer work –> may be similar DNA to functioning genes and can interrupt with medical diagnosis

Question 8

What is a processed gene

Answer 8

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

Question 9

Satellite DNA

Answer 9

Large blocks at centromeres and heterochromatic regions They are simple tandem repeats e.g. alphoid DNA at centres
Variable in size due to polymorphisms

Question 10

What is alphoid DNA

Answer 10

171bp repeat sequence at the centromeres and specific to chromosomes –> allows identification
Essential for assemnly of the controllers

Question 11

Alu Repeats

Answer 11

there are 500000 copies scattered within the genome, interspersed repeat. Dispersed due to retrotransposition and reintegration. Role in molecular pathology

Question 12

How do interspersed repeats cause problems

Answer 12

Chromosomes misalign in meiosis 1. Can cause Inrame deletion or out of frame

Question 13

Deletion/Insertion mutations

Answer 13

Variable effects. PCR May miss if heterozygous as still have 1 normal copy of the gene

Question 14

What is Duchenne

Answer 14

Deletion mutations

Question 15

What type of mutation is Charcol - Marie Tooth

Answer 15

Duplication mutations

Question 16

What type of mutation is haemophilia

Answer 16

Gross rearrangement

Question 17

Describe Haemophilia Mutations

Answer 17

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

Question 18

Point Mutation Description

Answer 18

May be silent or missense (Conservative or non-conservative)

Question 19

Where does hyper mutability occur?

Answer 19

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

Question 20

Describe nonsense mutations

Answer 20

substitutions, often produces stop codons causing truncated protines

Question 21

Frame shift mutations

Answer 21

Alters protein beyond the mutations, may truncate protein, commonly underlie genetic diseases

Question 22

What codes for a splice junctions

Answer 22

GT:AG –> mutations can change splice sites potentially leaving introns in the mRNA

Question 23

What is compound heterozygote?

Answer 23

has 2 recessive alleles for the same gene but alleys may be different to each other (i.e. mutated in a different place)

Question 24

Mutations heterogeneity is frequent or infrequent?

Answer 24

Frequent, where different mutations cause the same disease i.e. Cystic fibrosis and Beta thalassaemia

Question 25

Describe Hardy Weinberg Equation

Answer 25

p = mutant allele, q = normal allele (1-p) carrier = 2pq

Question 26

What does dominant inheritance sometimes cause

Answer 26

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

Question 27

Achrondroplasia descrive

Answer 27

Dominant mutations. Glycine to Arginine mutations

Question 28

Name the 3 types of trinucleotide repeat expansions (where 3 amino acids are repeated)

Answer 28

1) polyglutamine repeates
2) Large non-coding repeated
3) MUtational instability

Question 29

1) Polyglutamine repeats describe

Answer 29

CAG repeats involved in neurodegenerative disorders i.e. Huntingtons and Spinocereballar ataxia. Triplet repeats in the coding region

Question 30

1) Large non-coding repeats

Answer 30

Not in coding region

Fragile X syndome –> transcriptional silencing and Myotonic dystrophy

Question 31

Mutation Instability

Answer 31

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

Question 32

Describe Fragile X syndrome

Answer 32

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

Question 33

What is morphology

Answer 33

the study of the structure and form of animals and plants

Question 34

When is a malformation more likely to be genetic

Answer 34

if the mutation is multiple, dysmorphic and there is a familyy history

Question 35

Deep plantar creases associated with what trisomy

Answer 35

trisomy 8

Question 36

Are spina bifida and cleft lip isolated or genetic

Answer 36

Spina bifida is isolated, cleft lip is isolated but sometimes genetic

Question 37

22q11.2 Deletion

Answer 37

Degeorge Syndrome
Learning difficulties, cleft palate, velopharyngeal insufficiency, congenital heart disease, hypocalcaemia, seizures, immune defeciency, renal malformation

Question 38

Describe achondroplasia

Answer 38

Autosomal dominant –> often a mutation. Increased risk with increased paternal age! limb shortening, short stature, foramen magnum compression/hydrocephalus

Question 39

Beckwith-widemann syndrome

Answer 39

Large tongue, ear pits/creases, exomphalos, hemihypertrophy, neonatal hypoglycaemia
INCREASED RISK OF WILMS TIMOUR (nephroblastoma)

Question 40

Down syndrome - the commonest chromosomal disorder

Answer 40

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

Question 41

Kabuki Syndrome

Answer 41

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

Question 42

Mosaicism

Answer 42

Can cause hypo or hyper pigmented skin patches, may follow Blanschkos lines and diagnosis often requires skin biopsy

Question 43

Pseutz-Jeghers Sundrome

Answer 43

Gastrointestinal polyps can cause bleeding and obstructions

Malignancies –> colorectal, gastric, pancreatic, breast and ovarian

Question 44

Treacher Collins Syndrome

Answer 44

Autosomal dominant. Vary variable cleft lip and hearing impairment,

Question 45

Waardenburg syndrome

Answer 45

Sensorineural hearing impairment, iris heterochromia, premature greying, white forelock, areas of skin hypo pigmentation, congenital malformations (hirschsprungs/USD)

Question 46

Williams Syndrome

Answer 46

7q11 deletion
Learning difficulties, cocktail party speech, congenital heart diseases (supravalvular arctic stenosis and peripheral pulmonary artery stenosis). Hypercalcaemia)