Genetics

Question 1

where is DNA found in a cell?

Answer 1

• mainly in nucleus
• some found in mitochondria

Question 2

what is the structure of a chromosome?

Answer 2

• chromatin fibres made up of histones wrapped in DNA
• chromosomes come in pairs, one from the father and one from the mother

Question 3

what would we use to study chromosomes to identify abnormalities, congenital disorders, and cancer development?

Answer 3

• light microscopy

Question 4

what is the locus?

Answer 4

• the position of a gene on a chromosome

Question 5

what are the 4 DNA bases?

Answer 5

• Adenine and Thymine
• Cytosine and Guanine

Question 6

what does the centromere do?

Answer 6

• divides the chromosome into the short arm and longer arm

Question 7

what is the telomere?

Answer 7

• the structure at the end of a chromosome

Question 8

what is meant by the term genome?

Answer 8

• all of the DNA found in one cell
• the human genome is made up of nuclear and mitochondrial DNA sequences

Question 9

what are the aims of the human genome project?

Answer 9

• to determine the nucleotide sequence of the transcriptionally active parts of the human genome
• and to define the position (locus) of each gene on the chromosomes

Question 10

how many chromosomes do human cells contain?

Answer 10

• 46 chromosomes (23 pairs)

Question 11

how many protein-coding genes does the human genome contain?

Answer 11

• fewer than 20,000 protein-coding genes, but it also contains many other regulatory elements that affect the transcription and translation of genes

Question 12

what is meant by the term gene?

Answer 12

• a gene is a particular sequence of DNA found on a locus on a chromosome

Question 13

What is apoptosis and what is it characterised by?

Answer 13

• programmed cell death (characterised by chromatin degradation)

Question 14

What are the 3 main changes that occur when a cell becomes tumourigenic?

Answer 14

1. Immortilisation: property of indefinite growth
2. The cell fails to follow normal growth constraints: cell growth usually relies on the expression of growth factors, tumour cells become independent of these controls
3. Invasion: the ability to invade normal tissue and spread to other organs (metastasis)

Question 15

The cell depends on multiple extracellular signals…

Answer 15

• many cells require multiple signals (green arrows) to survive
• additional signals (red arrows) to divide
• and still other signals (black arrows) to differentiate

cell phenotype

Question 16

The hallmarks of cancer…

Answer 16

Question 17

What are the 3 types of heritable changes in cancer cells?

Answer 17

• dominant driver mutations in oncogenes
• recessive driver mutations in tumour suppressor genes
• epigenetic changes (the gene is not altered in DNA sequence)

Question 18

What can the heritable changes of cancer cells lead to in terms of functional change in the operation of the cell?

Answer 18

• a protein might be over expressed or under expressed
• a protein might change its function
• it might produce a change in the regulation of a pathway

Question 19

Types of changes in cancer genome…

Answer 19

Question 20

What are the 2 groups which mutations are separated into based on their effect on the function of a cell?

Answer 20

• Driver mutation: an alteration that gives a cancer cell a fundamental growth advantage for its neoplasmic transformation
• Passenger mutation: has no effect on the fitness of a clone but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation
  (many more passenger mutations than driver mutations)

Question 21

How do mutated oncogenes affect the way in which proteins are expressed?

Answer 21

• the protein expressed by a mutated oncogene usually has a lack of regulation or has increased activity

Question 22

What are leukemias?

Answer 22

• blood cancers

Question 23

Philadelphia chromosome…

Answer 23

• this is an example of chromosomal translocation
• this upregulates expression of an oncogene by fusing the gene with a promoter region that is always switched on or active

Question 24

What type of mechanism is seen in the MYC family of oncogenes to mutate/activate them which leads to increased expression of a protein?

Answer 24

• amplification
• this can mean that there are 10 to 100 copies of an oncogene sequence
• multiple copies of the oncogene leads to increased expression of the protein

Question 25

What is the normal role of tumour suppressor genes?

Answer 25

- to restrain uncontrolled cell division - eg. controlling the passage through the cell cycle so that any DNA damage can be repaired - eg. or by triggering apoptosis in response to DNA damage - (eg. TP53, Retinoblastoma gene)

Question 26

What is retinoblastoma and what is it caused by?

Answer 26

- Retinoblastoma is a human childhood disease involving a tumour of the retina - it is caused by loss of both copies of the RB gene on chromosome 13

Question 27

Are tumour suppressor genes dominant or recessive at cellular level?

Answer 27

- recessive

Question 28

What is the role of the TP53 gene?

Answer 28

- 'guardian of the genome' - regulates cell division - when there is DNA damage, the p53 protein has a role in deciding whether the cell can be repaired (activates other genes to fix the damage) or needs to be destroyed (p53 stops cell from dividing and signals apoptosis to occur) - (therefore the TP53 gene is frequently inactivated in cancers)

Question 29

Li Fraumeni syndrome is a rare autosomal disorder caused by what?

Answer 29

- caused by inherited mutations of TP53 - affected people are likely to develop cancer in their lifetime

Question 30

What are the 4 main risk factors associated with increased risk of cancer?

Answer 30

1. Germline or inherited mutations 2. Carcinogens 3. Age 4. Obesity (image shows diagram of preventable cancers)

Question 31

What is the difference between germline mutations and somatic mutations?

Answer 31

- germline mutations: occur in genome of the human body - somatic mutations: occur in genome of the tumour

Question 32

What are carcinogens and what are the 2 classes?

Answer 32

- Carcinogens may be chemicals, infectious agents, or different forms of radiation (eg. tobacco smoke, ionising radiation, sunlight etc.) 1. Initiators: that predispose cells to develop tumours 2. Promoters: stimulate tumour development

Question 33

How is obesity a risk factor in causing cancer?

Answer 33

- fat cells make extra hormones and growth factors - hormones and growth factors tell cells in our body to divide more often - this increases the chance of cancer cells being produced - which can then continue to divide and cause a tumour

Question 34

give two examples of autosomal recessive disorders

Answer 34

- cystic fibrosis - sickle cell anaemia

Question 35

give an example of an autosomal dominant disorder

Answer 35

- Huntington's

Question 36

what is a gene?

Answer 36

- a long, specific sequence of DNA that usually codes for proteins

Question 37

describe the structure of a chromosome

Answer 37

- chromatin fibres made up of proteins called histones wrapped in DNA - centromere divides the chromosome (short and long arm)

Question 38

how many chromosomes does a person have?

Answer 38

- 46 (23 pairs)

Question 39

Describe the major modes of Mendelian-monogenic inheritance

Answer 39

- Monogenic inheritance - caused by defects in one particular gene and often simple and predictable inheritance - but can be variable penetrance (chance that a genotype results in expected phenotype) - seen with eg Hereditary Heamochromatosis (low penetrance), Huntington’s Chorea (near complete penetrance) - and can be Mutifactorial (genetic + environmental)

Question 40

Describe polygenic inheritance, and discuss the contribution of genetic factors to commmon multifactorial diseases

Answer 40

- Polygenic inheritance = inheritance and expression of phenotype determined by many genes at different loci - traits with continuous distribution (eg. blood pressure and height) often determined by interplay of many alleles at different loci - Multifactorial: require interaction of environmental and genetic factors (eg. Diabetes, Cardiovascular Disease and Schizophrenia) - (note: can see in eg. twin studies - same genetic make up)

Question 41

What are the 3 types of alterations which functionally alter the cell as the cell reproduces which are inherited?

Answer 41

- Inactivation of tumour suppressor genes - normal role is to restrain uncontrolled cell division - Dominant activation of oncogenes - (oncogenes involved in pathways regulating growth) - Alterations in regulation of expression of genes (epigenetic changes - do not alter gene sequence but include DNA modifications such as methylation of DNA)) - (note: can lead to gene expression occurring in wrong place at wrong time)

Question 42

What are the two types of genetic mutation?

Answer 42

- DRIVER mutation: alteration in genome of a cancer cell that gives a growth advantage - PASSENGER mutation: no effect on fitness of cell but detected as in same cell as mutation in driver gene. Repliactes rapidly as cell multiplying rapidly = hitchhiker in evolutionary biology

Question 43

Discuss the patterns of inheritance and types of mutation associated with the common muscular dystrophies and ataxias

Answer 43

**Duchenne Muscular Dystrophy...** - X-linked recessive - alterations to Dystrophin coding gene (large gene) - incidence - 1 in 3500 males. - Dystrophin stops muscle cell membrane tearing with contraction and relaxation. - see increase in CK in blood **Becker Muscular Dystrophy...** - X linked - affects Dystrophin - milder than DMD therefore later onset **Myotonic Dystrophy:** Autosomal dominant **Friedrich’s Ataxia...** - progressive neurodegenerative movement disorder usually onset symptoms from 10-15 years age - autosomal Recessive 1 in 50 000 - affects ability to co-ordinate voluntary movements - trinucleotide repeat expansion **Autosomal Dominant Cerebellar Ataxia...** - Trinucleotide repeat expansion - onset as adult

Question 44

What are the features of Duchenne Muscular Dystrophy

Answer 44

- X linked recessive - Progressive degeneration of muscle fibres and Weakness - Dystrophin affected - 1 in 3500 males - Onset 3-5 years - Difficulty walking and Waddling gait - Gowers’ sign (getting up from floor by going on all fours and walking hands up legs) and Toe walking - Pseudohypetropy - especiallly calves as muscle replaced by collagen and adipose tissue - Scoliosis and Contractures - Low IQ - Dilated cardiomyopathy - Death 15-25 years from cardiac or respiratory failure

Question 45

What are features of Becker Muscular Dystrophy

Answer 45

- X linked recessive- in frame mutation of Dystrophin gene - 1 in 30000 males - Slowly progressive - Onset from 7 yeras (mean 11y) - Proximal muscle more affected - Gowers’ sign and Toe walking - Severity depends on Dystrophin levels (milder than Duchenne) - Calf pseudohypertrophy, cardiomyopathy, respiratory muscle involvement, scoliosis, mild learning difficulties

Question 46

Myotonic Dystrophy

Answer 46

- Autosomal dominant - 1 in 8000 - Adult onset - Slowly progressive multisystem - eg. myotonic facies, cardiomyopathy, muscle wasting, cataracts, endocrine - diabetes - Can show anticipation - disease gets progressively worse / symptoms earlier in generations

Question 47

Nucleic acids, genes, and genomes quiz Q1...

Answer 47

Question 48

Nucleic acids, genes, and genomes quiz Q2...

Answer 48

Question 49

Nucleic acids, genes, and genomes quiz Q3...

Answer 49

Question 50

Nucleic acids, genes, and genomes quiz Q4...

Answer 50

Question 51

Nucleic acids, genes, and genomes quiz Q5...

Answer 51

Question 52

Nucleic acids, genes, and genomes quiz Q6...

Answer 52

Question 53

Nucleic acids, genes, and genomes quiz Q7...

Answer 53