GENETICS

Question 1

Myotonic muscle dystrophy

Answer 1

Myotonic dystrophy is characterized by progressive muscle wasting and weakness. People with this disorder often have prolonged muscle contractions (myotonia) and are not able to relax certain muscles after use.

Question 2

Symptoms of myotonic muscle dystrophy

Answer 2

-muscle weakness,
- muscle spasm
which will affect their mobility.
-They will have an increased risk of getting
diabetes which might be difficult to
treat.
-They will have heart
problems. (abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects))
-They will have cataracts.
-They will have an increased risk to
sometimes tumours

Question 3

What causes duchenne muscular dystrophy

Answer 3

DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact.

Question 4

What is TRISOMY 21

Answer 4

downsydrome

Question 5

Types of Translocations

Answer 5

Reciprocal

robertsonian

Question 6

What is reciprocal translocation?

Answer 6

When a part of two chromosomes switches over

-As long as balanced = usually no harmful affects bc got the correct amount of info

Question 7

What is robertsonian transloacation?

Answer 7

When one chromosome attached to another so looks like 45 present

Question 8

A v common deletion syndrome

Answer 8

Chromosome 22q11 deletion syndrome

Question 9

Other names of 22q11 syndrome

Answer 9

Digeorge syndrome

Velocardialfacial syndrome

Question 10

Features of 22q11 Deletion Syndrome

Answer 10

Characteristic facial features (?)
Congenital heart disease (≈74%)
Palatal abnormalities	 (≈69%)	
Learning difficulties (≈70-90%)
Psychiatric problems (?)
Immunodeficiency (≈	77%)
Hypocalcaemia (≈50%)
Renal abnormalities (≈37%)
Approx. 90% de novo, 10% inherited

Question 11

Mendel’s 3 laws of genetics

Answer 11

• Segregation
• Dominance
• Independant assortment

Question 12

Allelic heterogeneity

Answer 12

where different mutations within the same gene result in the same clinical condition e.g. cystic fibrosis. Thus an individual with an autosomal recessive condition may be a compound heterozygote for two different mutations

Question 13

Features of Autosomal Recessive Inheritance

Answer 13

Male and females affected in equal proportions
Affected individuals only in a single generation
Parents can be related, i.e. consanguineous

Question 14

Most common Autosomal recessive condition

Answer 14

Cystic fibrosis

Question 15

Diagnostic test for cystic fibrosis

Answer 15

Sweat testing (not genetic analysis)- looks for increased Chloride ions in sweat

Question 16

Cystic fibrosis can be cvaused by over 1000 mutations this is called

Answer 16

Mutational heterogeneity

Question 17

What is cystic fibrosis

Answer 17

inherited condition that causes sticky mucus to build up in the lungs and digestive system. This causes lung infections and problems with digesting food.

Question 18

Symptoms of cystic fibrosis

Answer 18

recurring chest infections
wheezing, coughing, shortness of breath and damage to the airways (bronchiectasis)
difficulty putting on weight and growing
jaundice
diarrhoea, constipation, or large, smelly poo
a bowel obstruction in newborn babies (meconium ileus) – surgery may be needed

Question 19

Why does cystic fibrosis cause so many problems

Answer 19

The build-up of sticky mucus in the lungs can cause breathing problems and increases the risk of lung infections. Over time, the lungs may stop working properly.

Mucus also clogs the pancreas (the organ that helps with digestion), which stops enzymes reaching food in the gut and helping with digestion.

This means most people with cystic fibrosis don’t absorb nutrients from food properly and need to eat more calories to avoid malnutrition.

Question 20

Genotype - phenotype correlations in cystic fibrosis EXample

Answer 20

If have F508 mutation in both alleles then =
pancreatic insufficiency and chronic lung disease

If have F508 in one allele and R117H in other = majority are pancreatic sufficient but have chronic lung disease - Milder symptoms

Question 21

Consanguinity meaning

Answer 21

Reproductive union between two relatives.

Question 22

Autozygosity

Answer 22

Homozygosity by descent, i.e. inheritance of the same altered allele through two branches of the same family.

Question 23

Typical features of autosomal dominant inheritance

Answer 23

Male and females affected in equal proportions
Affected individuals in multiple generations
Transmission by individuals of both sexes, to both sexes
But don’t forget penetrance & variability!

Question 24

Pentrance meaning

Answer 24

The percentage of individuals with a specific genotype showing the expected phenotype

Question 25

Expressivity

Answer 25

Refers to the range of phenotypes expressed by a specific genotype

Question 26

Meaning of de novo mutation and example of disease caused by this

Answer 26

New mutation - Example – Neurofibromatosis type 1, up to 50% of cases occur as result of de novo mutation

Question 27

What is neurofibromatosis

Answer 27

genetic condition that causes tumours to grow along your nerves. The tumours are usually non-cancerous (benign) but may cause a range of symptoms.

Question 28

Symptoms of neurofibromatosis

Answer 28

pale, coffee-coloured patches (café au lait spots) soft, non-cancerous tumours on or under the skin (neurofibromas) clusters of freckles in unusual places – such as the armpits, groin and under the breast problems with the bones, eyes and nervous system

Question 29

Anticipation meaning and example of disease

Answer 29

Whereby genetic disorder affects successive generations earlier or more severely, usually due to expansion of unstable triplet repeat sequences Example Myotonic dystrophy

Question 30

Somatic Mosaicism

Answer 30

Genetic fault present in only some tissues in body

Question 31

Gonadal (germline) Mosaicism

Answer 31

Genetic fault present in gonadal tissue

Question 32

Late-onset

Answer 32

Condition not manifest at birth (congenital), classically adult-onset Example – Hypertrophic Cardiomyopathy

Question 33

Sex-limited

Answer 33

Condition inherited in AD pattern that seems to affect one sex more than another Example – BRCA1/2

Question 34

Predictive testing

Answer 34

Testing for a condition in a pre-symptomatic individual to predict their chance of developing condition

Question 35

Lyonization (X-inactivation)

Answer 35

Generally only one of two X chromosomes active in each female cell. Can be skewed

Question 36

Genomic imprinting

Answer 36

is an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner

Question 37

Homoplasmy

Answer 37

a eukaryotic cell whose copies of mitochondrial DNA are all identical (identically normal or have identical mutations)

Question 38

Why do syndormes like prader-willi or angelmans arise?

Answer 38

Activity of the gene is parent dependent but that gene is switched off (usually both genes active and working )

Question 39

Heteroplasmy

Answer 39

there are multiple copies of mtDNA in each cell the name given to denote mutations which affect only a proportion of the molecules in a cell the level of heteroplasmy can vary between cells in the same tissue or organ, from organ to organ within the same person, and between individuals in the same family

Question 40

Carrier testing for what?

Answer 40

Autosomal recessive diseases

Question 41

Predictive testing for what ?

Answer 41

Late onset diseases

Question 42

Whats Sanger sequencing

Answer 42

Developed by Frederick Sanger in 1977 Uses PCR to amplify regions of interest followed by sequencing of products Useful for single gene testing

Question 43

Next generation sequencing

Answer 43

High throughput or massively parallel sequencing Can sequence whole human genome in one day Multi-gene panels, whole exome/genomes

Question 44

Pyloric stenosis

Answer 44

Pyloric stenosis is a condition where the passage (pylorus) between the stomach and small bowel (duodenum) becomes narrower.

Question 45

Characteristics of multifactorial inheritance and example

Answer 45

If the condition is more common in one particular sex, then relatives of an affected individual of the less frequently affected sex will be at higher risk than relatives of an affected individual of the more frequently affected sex.

Question 46

The Liability model explain

Answer 46

The factors that influence the development of a multifactorial disorder, genetic and environmental can be considered as a single entity known as liability the liabilities of all individuals form a continuous variable which has a normal distribution the curve for relatives is shifted to the right compared to the general population the closer the relationship the greater the shift to the right a threshold exists above which the abnormal phenotype is expressed in the general population the proportion beyond the threshold is the population incidence and among relatives is the familial incidence

Question 47

GWAS – Genome wide association studies

Answer 47

Utilises the fact that a gene can have several variants –alleles compare the frequency of markers in a sample of patients and a sample of healthy controls. Can use candidate genes or nowadays try to aim for complete coverage of the genome Look for markers e.g. a SNP that is seen more frequently in the disease population Sequence that area to try to identify the gene and the particular allele that is associated with the increased likelihood of developing the condition

Question 48

Is gene variation always pathogenic?

Answer 48

Some variations in a gene cause that gene to be inactivated or behave abnormally – pathogenic Most genetic variation still results in a functioning gene – polymorphisms Different types of polymorphisms – e.g. SNPs (single nucleotide polymorphisms), differing lengths of a CA repeat.

Question 49

Anabolic

Answer 49

synthesise larger molecules from smaller components Eg storage biosynthetic

Question 50

Catabolic

Answer 50

break down larger into smaller | Oxidative

Question 51

How is carb stored

Answer 51

as glycogen in liver and muscles

Question 52

how is protein stored

Answer 52

Muscle

Question 53

How is fat stored

Answer 53

As adipose tissue

Question 54

Basal Metabolic Rate (BMR)

Answer 54

A measure of the energy required to maintain non-exercise bodily functions such as; ``` respiration, contraction of the heart muscle, biosynthetic processes, repairing & regenerating tissues, ion gradients across cell membranes. ``` Approximately 1kcal/kg body mass/hour essentially Energy needed to stay alive at rest

Question 55

Conditions essential for measuring BMR

Answer 55

Post-absorptive (12 hour fast) • Lying still at physical and mental rest • Thermo-neutral environment (27 – 29oC) • No tea/coffee/nicotine/alcohol in previous 12 hours • No heavy physical activity previous day • Gases must be calibrated • Establish steady-state (~ 30 minutes) * If any of the above conditions are not met, then = Resting Energy Expenditure (REE)

Question 56

Factors affecting BMR if decreasing

Answer 56

``` Decreasing BMR Age Gender Dieting/Starvation Hypothyroidism Decreased muscle mass Drugs ```

Question 57

Factors affecting increasing BMR

Answer 57

``` Increasing BMR Body weight (BMI) Hyperthyroidism Low ambient temp. Fever/infection/chronic disease Caffeine/stimulant intake Exercise Pregnancy & lactation ```

Question 58

What is refeeding syndrome?

Answer 58

is a serious potential complication of commencing feeding in children and young people who have experienced starvation.

Question 59

What does refeeding syndrome cause? `

Answer 59

Re-distribution of phosphate, potassium, magnesium etc due to insulin, - Can be fatal Switch back to carbohydrates as the main fuel which requires phosphate and thiamine. - Therefore thiamine sometimes given before feeding

Question 60

What is Malnutrition

Answer 60

A state of nutrition with a deficiency, excess or imbalance of energy, protein or other nutrients, causing measurable adverse effects

Question 61

There are two main types of polyunsaturated fats:

Answer 61

omega-3 and omega-6.

Question 62

Why should we eat fish oil

Answer 62

Some types of omega-3 and omega-6 fats cannot be made by the body and are therefore essential in small amounts in the diet, mainly in plant and fish oils.

Question 63

Why do we need vitamin C and where do we get it from?

Answer 63

- Ascorbic acid - Fruit and vegetables - Heat labile - Collagen synthesis - Improve iron absorption - Antioxidant

Question 64

Why do we need vitamin B12 and where do we get it from? | Cobalamin

Answer 64

``` Protein synthesis DNA synthesis Regenerate folate (and therefore – cell division) Fatty acid synthesis Energy production ``` Works with the vitamin folate to make DNA. Helps to make healthy blood cells. Low levels of vitamin B12 can cause a type of anaemia. Keeps nerves working properly. Found in eggs, meat, poultry, shellfish, milk

Question 65

Vitamin B1 | Thiamine

Answer 65

Helps with energy production in your body.

Question 66

Vitamin B2 | Riboflavin

Answer 66

Helps with energy production in your body. | Helps your body use other B vitamins.

Question 67

Vitamin B3 | Niacin

Answer 67

Helps your body to use protein, fat and carbohydrate to make energy. Helps enzymes work properly in your body.

Question 68

Biotin

Answer 68

Allows your body to use protein, fat and carbohydrate from food.

Question 69

``` Vitamin B6 (Pyridoxin) ```

Answer 69

Helps your body to make and use protein and glycogen which is the stored energy in your muscles and liver. Helps form haemoglobin which carries oxygen in your blood.

Question 70

Folate
(also known as folic acid)

Answer 70

Helps to produce and maintain DNA and cells. Helps to make red blood cells and  prevent anaemia. Getting enough folic acid lowers the risk of having a baby with birth defects like spina bifida.

Question 71

Vitamin C

Answer 71

May help prevent cell damage and reduce risk for certain cancers, heart disease and other diseases.
Collagen synthesis - helps heal cuts and wounds and keeps gums healthy.
Protects you from infections by keeping your immune system healthy.
Increases the amount of iron your body absorbs from some foods.

Question 72

Vitamin A

Answer 72

Helps you to see in the day and at night. Protects you from infections by keeping skin and other body parts healthy. Promotes normal growth and development.

Question 73

Carotenoids

Answer 73

Carotenoids are not vitamins but some types can turn into vitamin A in the body. Act as antioxidants which protect your body from damage caused by harmful molecules called free radicals.

Question 74

Vitamin D

Answer 74

Increases the amount of calcium and phosphorus your body absorbs from foods. Deposits calcium and phosphorus in bones and teeth, making them stronger and healthier. Protects against infections by keeping your immune system healthy.

Question 75

Vitamin E

Answer 75

Helps to maintain a healthy immune system and other body processes.

Question 76

Vitamin K

Answer 76

Makes proteins that cause our blood to clot, when you are bleeding. Involved in making body proteins for your blood, bones and kidneys.

Question 77

Sodium

Answer 77

Needed for fluid balance, nerve conduction, and muscle contraction

Question 78

Chloride

Answer 78

Needed for fluid balance, stomach acid

Question 79

Potassium

Answer 79

Needed for fluid balance, nerves and muscles

Question 80

Calcium

Answer 80

Important for healthy bones | and teeth; etc.

Question 81

Phosphorus

Answer 81

Important for healthy bones | and teeth; found in every cell.

Question 82

Magnesium

Answer 82

Found in bones and all cells.

Question 83

Sulfur

Answer 83

Found in protein molecules