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Flashcards in GiM lectures 9,10,11 Deck (45):
1

What is morphology

scientific study of the structure and form of either animals and plants or words and phrases

2

What % of births have congenital malformations?
- when are these malformations more likely to be genetic?

2-3%

multiple malformations, dysmorphic, family history

3

22q11.2 Deletion
- phenotype
- frequency
- dysmorphology
- also known as?

Very variable phenotype
1/5000
Learning difficulties - 70%
Congenital heart defects 75%
hypocalcaemia
Seizures
Immune deficiency
Renal malformation
Velopharyngeal insufficiency 32%
Cleft palate 15%
small lip and lower jaw
slanted eyes
short stature

aka - DiGeorge syndrome

4

Achondroplasia
- frequency
- mutation type
- risk factors?
- clinical features

1/20,000
autosomal dominant - often denovo
- increased with paternal age
- rhizomelic limb shortening
- short stature
- foramen magnum compression
- hydrocephalus

5

Beckwith-Wiedemann syndrome
- frequency
- clinical features

1/10000
Large tongue, ear pits/creases, exomphalos (umbilical herniation of guts), hemihypertrophy, neonatal hypoglycaemia,
microcephaly
increased risk of Wilms tumour

6

Down syndome
- frequency
- clinical features

1/800
learning difficulties, congenital heart defects, hypotonia in neonates, single palmar crease, cataracts, hearing impairment, hypothyroidism, leukaemia, atlanto-axial instability, alzheimers

7

What % of the normal population have a single palmar crease?
- unilateral
- bilateral

unilateral = 4%
bilateral = 1%

8

Kabuki syndrome
- frequency
- clinical features

1/30,000
learning difficulities, congenital eart disease 50%, poor growth, hearing impairment, cleft palate, premature breast development, persistent fetal finger pads 96%, flat broad nose, everted eyelids, cleft palate

9

mosaicism
- how is it diagnosied
- how can it be recognised

diagnosis by skin biopsy

can be hypo/hyper pigmented patches - may follow blaschko's lines

10

What are blaschko's lines

Blaschko lines are thought to represent pathways of epidermal cell migration and proliferation during the development of the fetus. only visible when a condition affecting the skin is present

11

Peutz-Jeghers Syndrome
- frequency
- clinical features

12

Treacher collins syndrome
Frequency
inheritance
clinical features

1/50000
autosomal dominant
very variable phenotype
cleft palate, hearing impairment,

13

Waardenburg syndrome
- frequency
- clinical features

1/250000
sensorineural hearing impairment, irisheterochromia, premature greying, white forelock, areas of skin hypo pigmentation, congenital malformations VSD, hirschprungs

14

William's syndrome
- what is it
- frequency
- clinical features

7q11 deletion
1/20,000
learning difficulties
cocktail party speech
congenital heart disease - supravalvular aortic stenosis, peripheral pulmonary artery stenosis
hypercalcaemia,
wide mouth, sunken nasal bridge,

15

What is cocktail party speech

able to speak fluently in small talk but unable to go into deeper complex social issues due to learning difficulties

16

What is the structure of DNA

deoxyribose ring
(5 carbons)
-OH on C1,3,5
C1 - binds to nucleotide base
C3 - binds to phosphate
C5 - binds to phosphate
DNA is stable
RNA is unstable (transient

17

What direction is DNA/RNA synthesised

5' to 3'

18

What does the shorthand DNA sequence of
5' AACGT represent

5' AACGT
TTGCA 5'

Sense strand is the one written and is the one that makes the mRNA

19

What is the haploid genome size of the following organisms
1) Mycoplasma genitalium
2) E. Coli
3) Schizosaccharomyces pombe
4) Caenorhabditis elegans
5) drosophila melanogaster
6) Human
7) salamander

1) 0.6Mbp
2) 5Mbp
3) 14 Mbp
4) 80Mbp
5) 165Mbp
6) 3000Mbp
7) 50000Mbp

20

Facts about the Human genome
- how many Mb dsDNA are there per haploid genome?
- What is the size of the largest and smaller chromosome
- what % of DNA is non coding
- How many protien coding genes are there

- 3 000 Mb dsDNA per haploid genome
-Chromosome 1 – 263 Mb
-Chromosome 22 – 39 Mb
->90% is non-coding DNA
-Approx. 20 000 protein-coding genes

21

What are single copy sequences in the human genome

genes

22

what are repetitive sequences within the human genome

Interspersed repeats - e.g. Alu repeats

Satellite DNA - large blocks or repetitive sequence, heterochomatin

23

What are Genes?

Functional unit of DNA
Transcription - copied to RNA
Translation - RNA to protein

Components of genes
exons, introns, regulatory sequences (promoters, enhancers, locus control regions)

24

What parts of protein synthesis occur in the nucleus

What parts of protein synthesis occur in the cytoplasm

Transcription, capping, cleavage and polyadenylation,

(splicing - takes RNA out into cytoplasm)

mRNA - Translation
Protein created
(post translational modificaitions)

25

What is alternative splicing

Exon Skipping
can lead to multiple mRNA forms - depending on how splicing occurs

26

What are gene families

All genes have an ancestral gene

Evolution of genes progress via duplication and divergence
most have similar structural families

Psuedogenes - are genes that have lost the function to express - often occur by accumulation of mutation in gene not essential for survival

27

Explain Processed genes

intron less copied of other genes - remote from parent gene

dispersed by reverse transcription and reintegration

some remain functional (e.g. PGK2 testis specific) but majority non functional

often one mutation away from becoming pseudogenes

28

How many of each of the following are present in the human genome

1) coding genes
2) short non coding genes
3) long non coding genes
4) pseudogenes
5) gene transcripts

Coding genes: 20,769
Short non-coding genes: 9,079
Long non-coding genes: 13,564
Pseudogenes: 14,165
Gene transcripts: 195,565

29

What is satellite DNA

Large blocks at centromeres and heterochromatic chromosomal regions
Simple tandemly repeated sequences
Many types e.g. alphoid DNA
Centromere repeat
Chromosome-specific
Size of blocks may be polymorphic
1, 9, 16, Y

30

What is Alphoid DNA

-type of satellite DNA found at centromeres
-171bp repeat unit
-chromosome specific variation
-needed for assembly of centromere

31

Explain interspersed repeats

scattered around genome
individual copies present at many location,

e.g. Alu repeat
500000 copies, 300bp, 5% genome
Dispersed by retrotransposition
can cause huntingtons

32

Causes of molecular pathology

Interspersed repeats causing unequal crossing over due to misalignment of sequence
- results in frameshift +/- truncation

33

What are the types of mutation
with examples

-Deletions and insertions
Duchenne muscular dystrophy = deletion
-Charcot-Marie-Tooth Disease = duplication
-Gross Rearrangement - haemophilia A
-Point mutation
-trinuceoptid repeat expansion - huntingtons

34

What is the haemophilia A mutation

Xq28
Inversion of homologous sequence within chromosome

35

what are the types of point mutation?

Silent
- if common = polymorphism
- causes same ammino acid to be coded for but by differnet codon

Missense
- causes different amnio acid
- can be conservative (within same amnio acid type)
- can be non conservative (different type of amnio acid, generally more damaging)

Non sense
no amnioacid coded for
truncated protein produced
can be detected

Frameshift mutation
alters protein sequence beyond mutation
truncated protein

36

What are the groups of amino acids?
Acidic
Basic
Polar
Non polar
aromatic
other

Acidic: Glu Asp
Basic: Lys Arg
Polar: Ser Thr Asn Gln Ser (His)
Non-polar:Ala Val Leu Ile Met
Aromatic: Phe Tyr Trp (His)
Other: Gly Pro

37

what is the most common point mutation

CG --> TG =1/3 of mutations

due to hyper mutability of CpG dinucleotides
- methylation of C (addition of CH3)
- deamination (change of C to T)
- Mismatch repair G-->A

38

Mutation nomenclature

reference sequence needed
genomic DNA, cDNA, Protein
(g.), (c.), (p.)

39

What is the mutational spectrum

loss of function mutations usually recessive
50% gene function is adequate
mutational heterogeneity is frequency - affected indivuals can be compound heterozygotes, mutation testing therefore challenging

40

give 2 examples of a recessive condition where the affected individual are compound heterozygotes

cystic fibrosis
beta thalassaemia

41

What is the carrier frequency equation?

p = mutant allele freq
q = 1-p = normal allele freq
p2 = affected individual
2pq = 2p(1-p) = carriers

42

What does dominant inheritance often result in?

gain or alteration of function

- smaller mutational spectrum
- new mutation comparatively common
- e.g. achondroplasia
FGFR3 G380R

43

what disease are caused by Polyglutamine repeats (CAG)

Neurodegenerative disorders
- huntington's disease
- spinocerebellar ataxias

44

What disease are caused by large non-coding repeat expansions

- fragile X syndrome - CGG repeat expansion (transcriptional silence)
- myotonic dystrophy

45

What diseases have occasional and frequent instability

occasional = huntington's
frequent = fragile X