Gen

Question 1

What are the single congenital defects

Answer 1

Malformation
disruption
Deformation
dysplasia

Question 2

What are the multiple congenital defects

Answer 2

Sequence
syndrome
Association

Question 3

Define malformation

Answer 3

Primary structural defect

As a result of intrinsically abnormal development

Question 4

Define disruption

Answer 4

Defect as a result of extrinsic interference with originally normal development

Question 5

Define Deformation

Answer 5

Mechanical force is causing abnormal shape, form or position

Distorting structure

Question 6

Define dysplasia

Answer 6

Abnormal organisation of cells in a tissue

Question 7

Define sequence

Answer 7

Pattern of multiple abnormalities

Derived single known prior anomaly or factor

Question 8

Define syndrome

Answer 8

Multiple abnormalities
Pathogenically related
Specific underlying cause

Eg. Downs

Question 9

Define Association

Answer 9

Non-random occurrence of abnormality

not explained by syndrome due to unknown cause

Question 10

What are the three problems that can occur with chromosomes

Answer 10

Aneuploidy- loss or gain of chromosomes
Structural- translocations, deletions, insertions, inversions, rings
Mosaicism- different cell lineages

Question 11

Transfer of genetic material from one chromosome to another is normal in balanced translocations unless…

Answer 11

Disruption of a gene

Fusion product

Question 12

Define monosomy

Answer 12

Loss of a single chromosome almost always lethal

Question 13

Define trisomy

Answer 13

Gain of one chromosome can be tolerated for specific chromosomes

Question 14

Define Mosaicism

Answer 14

Where different cells in the same individual have different numbers or arrangements of chromosomes

Question 15

What type of trisomy is the most common

Answer 15

Trisomy 16

Fatal in Utero -miscarriage

Question 16

What types of trisomies can be viable

Answer 16

13, 18, 21

13- patau syndrome
Heart defects, mental retardation

18- Edwards syndrome
Heart defects, kidney malformation, digestive tract defects, mental retardation

Question 17

What are the clinical features of down syndrome

Answer 17

Newborn period
Hypotonia, lethargic, eXcesS nuchal skin

Craniofacial
Macroglossia, small ears, sloping palpebral fissures

Limbs
Single Palmar crease, wide gap between first and second toes

Other
Short stature, douodenal atresia
Low IQ but advanced social skills

Question 18

What are the three different chromosome aberrations which lead to downs

Answer 18

Trisomy 21
90% due extra chromosome from mum
Non-disjunction homologous chromosomes in meiosis 1 (3 copies instead of 2)

Translocation
Break In Acrocentric chromosomes (13,14,15,21,22) and fusion long arms
No. Chroms still 46 but part/full copy chrom 21 attaches another chrom

Mosaicism
Mix of two types of cells some containing 46 chromosomes some containing 47

Question 19

What is Monosomy X

Answer 19

Turner’s syndrome
Loss of X or Y in paternal meiosis
(Other causes: ring chromosome, single arm deletion, Mosaicism)

Question 20

What are the characteristics of Turner’s

Answer 20

Prenatal
Generalised oedema and neck swelling

Newborn/child
Odematous hands and feet, Webbed neck, low set ears, low posterior hairline, broad chest, aortic defects, urinary defects

Adult
Short stature, infertility, diabetes, hypothyroidism

Normal intelligence

Question 21

What is XXY

Answer 21

Klinefelter’s syndrome
Phenotypically male
Learning disability
Tall and infertile

Question 22

Define dosage compensation

Answer 22

Process by which organisms equalise expression of genes between members of different biological sexes

Question 23

What are the two mechanisms of dosage compensation

Answer 23

1. Random in activation of single X-chromosome in females

2. Increased (2x) expression of X-chromosome genes in males

Question 24

Explain why sex determination is not solely based on sex chromosome karyotype and how it is possible to be chromosomally one gender and phenotypically opposite

Answer 24

SRY gene - testes development

This gene can be translated to X-chromosome in SRY recombination

XX males develop testes but are sterile because other Y-chromosome genes important in spermatogenesis

XY females infertile

Question 25

What are the characteristics of a monogenic disorder | List examples

Answer 25

Clear inheritance no environment individually rare Eg. Huntington’s cystic fibrosis and haemophilia

Question 26

What are the characteristics of a complex disorder | List examples

Answer 26

No clear inheritance Environment essential Common Eg. Type II diabetes, schizophrenia

Question 27

Define polymorphism

Answer 27

Mutation at >1%freq. in given population

Question 28

Why are pedigree diagrams important

Answer 28

``` Identify genetic disease running in family Identify inheritance patterns Aid diagnosis Assist in management of condition Identify relatives at risk of disease ```

Question 29

Difference btwn autosomal recessive and autosomal dominant

Answer 29

At least one parent affected in autosomal dominant whereas no affected parent in autosomal recessive

Question 30

Example of autosomal dominant disease

Answer 30

``` Huntington’s disease Cell death in Basal ganglia Unstable CAG triplet repeats 10-35 unaffected 27-35 unaffected, risk affected kid 35-40 sometimes affected 40+ affected ```

Question 31

What is example of an autosomal recessive disease

Answer 31

Cystic fibrosis Mutation CFTR gene chrom 7 Coding chloride channel

Question 32

What is special about X-linked recessive diseases

Answer 32

No affected parents Transmitted by carrier female Only male affected

Question 33

Example of an ex-linked recessive disease

Answer 33

Haemophilia Blood clotting disorder causing easy bruising and heavy bleeding A and B (rarer) types Haemophilia A -F8 Haemophilia B -F9 Both genes are on the X-chromosome

Question 34

What are the three types of genetic heterogeneity

Answer 34

Same gene, different mutations leading to different symptoms Same disease, different genes Same disease, different genes, different inheritance patterns

Question 35

Define incomplete penetrance

Answer 35

Symptoms are not always present in an individual with a disease causing mutation

Question 36

Define variable expressivity

Answer 36

Disease severity may vary between individuals with the same disease causing mutation

Question 37

Define phenocopy

Answer 37

Having the same disease but with a different underlying cause

Question 38

Explain mechanisms of dominant conditions

Answer 38

Mutations leading to toxic protein effects of mutated gene which mask normal copy

Question 39

Explain mechanisms of recessive conditions

Answer 39

Mutations cause an absence of a functional protein so the normal copy is absent

Question 40

How can you treat dominant conditions

Answer 40

Neutralise the toxic protein effects or switch off the mutant gene

Question 41

What is Genomic imprinting

Answer 41

You inherit two copies of genes one from mother one father usually both copies of the each gene active but sometimes one copy is turned on which copy is made active depends on parent of origin some genes and only active only when inherited from father etc.

Question 42

What is uniparental disomy

Answer 42

A person receives two copies of chromosome or part of a chromosome from one parent and no copies from the other parent

Question 43

Two examples of uniparental dysomy

Answer 43

Prader Willi syndrome and Angelman syndrome

Question 44

What are the symptoms of Prada Willi syndrome

Answer 44

Due loss Paternal chr15 ``` Hyperphagia leading to obesity Mental impairment Behavioural problems Muscle hypotonia Short stature small hands and feet Delayed or incomplete puberty Infertility ```

Question 45

What are the symptoms of Angelman syndrome

Answer 45

Due loss maternal chr15 Developmental delay and speech impairment Movement disorder Behavioural uniqueness e.g. happy demeanours, excitable, short attention span Seizures

Question 46

List examples of mitochondrial disorders

Answer 46

MELAS LHON

Question 47

Describe symptoms LHON

Answer 47

More common in males Degeneration of retinal ganglion cells Loss of central vision Most become blind

Question 48

Describe symptoms MELAS

Answer 48

Progressive and ultimately fatal Muscle weakness vomiting headache dementia Single mutation in several genes

Question 49

List two examples of inborn errors of metabolism currently included in UK national neonatal screening programs

Answer 49

Phenylketonuria PKU MCADD DEFICIENCY

Question 50

Describe what PKU is

Answer 50

Inborn errors of metabolism and included in the UK national neonatal screening programs Blonde hair/blue eyes no melanin eczema and must Odour

Question 51

Describe what MCADD Deficiency is

Answer 51

Inborn errors of metabolism and currently included in UK national neonatalscreening program Most common disorder of fatty acid oxidation Medium chain acyl CoA dehydrogenase

Question 52

Treatment of PKU

Answer 52

Remove Phenylalanine from diet Protein supplements to supply other AAs Strict diet in preg Early detection

Question 53

Treatment of MCADD deficiency

Answer 53

Avoid fasting | Nutritional supplements at times of increased stress

Question 54

What is the difference between somatic and germline mutations

Answer 54

Somatic occurs in body cells and cannot be passed on to offspring Germline mutations in gametes which can be passed on to offspring

Question 55

What is the difference between driver and passenger mutations

Answer 55

Passengers are mutations that don’t contribute to the development of cancer but have occurred during growth cancer Drivers contribute to cancer development

Question 56

What are oncogenes

Answer 56

Promotes growth and proliferation in cells Signal in cascades and mitogenic pathway activation E.g..growth factors, transcription factors, tyrosine kinases

Question 57

What are tumour suppressor is

Answer 57

Regulate cell division, DNA damage checkpoints, Apple ptosis, DNA repair