2D Genetics

Question 1

What is genetics?

Answer 1

The study of how information is passed on from parents to their offspring and how characteristics and diseases are inherited

Question 2

What is genomics?

Answer 2

The study of all the genes in an individual

Question 3

Outline the basics of genetics

Answer 3

• Most genetic material is in chromosomes in the cell nucleus
• Each cell has 22 pairs of autosomes and one pair of sex chromosomes
• Some DNA is also in the mitochondria (inherited maternally)
• DNA made up of nucleotide bases: arginine, cytosine, thymine and guanine
• Groups of three bases form a codon
• Each codon encodes a specific amino acid
• Amino acids are the building blocks of proteins
• Only about 2% of the genome is codons (exons)
• The rest is introns - these have regulatory functions

Question 4

Outline the basics of protein production

Answer 4

• Transcription: DNA acts as a template to produce RNA
• Splicing: introns are removed
• Exporting: messenger RNA leaves the nucleus
• Translation: mRNA is used to make protein chains; protein chains form peptides or polypeptides
• These produce proteins which then fold to assume a 3D functional form
• Translocation: proteins are moved to where they are needed in the cell

Question 5

Why does genetic material vary between individuals?

Answer 5

1. Maternal and paternal DNA shuffled during meiosis
2. Alterations to DNA during cell division (can be due to chance or environmental hazards)
3. Epigenetic alterations that affect how the genome is expressed (these can be heritable)

Question 6

Difference between genotype and phenotype?

Answer 6

Genotype describes all the alleles in one individual’s genome.

Phenotype describes the physical characteristics expressed in a person as a result of their genotype.

Question 7

Why can genotypes result in variable phenotypes?

Answer 7

1. Incomplete penetrance of the gene e.g. Huntington’s can have 100% penetrance whereas BRCA is lower
2. More than one mutation of a gene associated with a certain characteristic e.g. CF
3. More than one gene relating to the characteristic

Question 8

Define penetrance

Answer 8

The proportion of people with a given genotype that express its phenotype

Question 9

What are the broad inherited causes of disease in a population

This is broader than AD, AR, X-linked etc

Answer 9

1. Multifactorial disease
   - Multiple environmental and genetic factors affect disease risk e.g. CHD, diabetes
   - In some cases a single gene may be strongly (but not definitively) associated with development of disease e.g. BRCA
2. Single gene disorders aka Mendelian disease
   - One altered gene responsible for a disease
   - E.g. CF or Huntington’s
3. Chromosomal abnormalities
   - Number of chromosomes: e.g. Down’s syndrome
   - Structural abnormalities in chromosomes e.g. Charcot-Marie-Tooth (neuropathy caused by duplication of part of chromosome 17)

Question 10

Outline the different types of Mendelian inheritance and give examples

Answer 10

AD
- Only need one copy of the gene to have the disease
- If one parent has the disease, child has 50% chance of inheriting
- There is no carrier state
- Huntington’s, familial hypercholesterolaemia

AR
- Both copies of the gene must be abnormal for the individual to be affected
- Individual with one copy of the gene are asymptomatic carriers
- Where both parents are carriers, 25% chance of the child having the disease
- 50% chance that child will be carrier
- CF, sickle cell, PKU

X-linked recessive
- Males more likely to be affected and females more likely to be carriers
- All daughters of affected men will be carriers
- None of the sons of affected men will be affected
- Haemophilia, Duchenne muscular dystrophy

X-linked dominant
- Very rare
- Occur when single copy of a gene on the X chromosome is mutated
- Coffin-Lowry sundrome

Y-linked
- Very rare
- Male infertility

Question 11

What are non-Mendelian patterns of inheritance

Answer 11

• Multifactorial diseases e.g. polygenic diseases
• Mitochondrial diseases (always inherited maternally)

Question 12

Outline the basics of mitochondrial inheritance

Answer 12

• Maternal inheritance of mitochondrial DNA
• Mitochondrial DNA encodes genes responsible for energy production in the cell
• Threshold effect, where a child has to inherit a certain proportion of mutated DNA in order to be symptomatic

Question 13

What are polygenic disorders?

Answer 13

Conditions where several gene variants increase susceptibility to disease

Question 14

What are the challenges in identifying genes in polygenetic disorders?

Answer 14

1. Many susceptible alleles so need very large sample sizes to detect statistically significant gene effects
2. Studies in different populations may identify different genes due to different population gene pools or different environments
3. Because disease biology is incompletely understood, genome-wide scans have to be done rather than candidate gene studies (which is presumably more laborious)

Question 15

How can gene-environment interactions affect disease risk?

Looking for specific mechanisms

Answer 15

• Infections e.g. HIV and Burkitt’s lymphoma
• Chemicals e.g. carcinogens in tobacco smoke and lung Ca
• Physical hazards e.g. radiation and cancer
• Nutritional exposures e.g. phenylalanine and PKU
• Behaviours eg. physical inactivity and obesity

Question 16

What is pharmacogenetics?

Answer 16

Uses an individual’s genetics as basis for understanding relative effectiveness of different pharmaceutical treatments

Question 17

What is gene therapy?

Answer 17

Use of vehicles such as viruses or plasmids to insert genetic material into the cells of people with a particular disease e.g. modified stem cells in people with SCID to produce a missing enzyme

Question 18

What are two types of genetic testing in relatives of someone with a disease

Answer 18

1. Predictive testing: used when someone has family history of a disease that develops in adulthood with high penetrance e.g. Huntington’s, BRCA-related breast Ca
2. Individual carrier testing: used in asymptomatic individuals with a family history of an autosomal or X-linked disorder e.g. CF

Question 19

What are the ways of controlling a disease with a genetic component?

Answer 19

1. Preimplanation genetic testing
2. Antenatal testing and screening
3. Earlier/more frequent screening or preventative surgery e.g. with breast Ca
4. Treatment to reduce disease risk e.g. statins for people with familial hypercholesterolaemia
5. Genetic counselling to understand disease risk and make decisions

Question 20

What is molecular biology?

Answer 20

Study and manipulation of biological processes and structures at a molecular level

Question 21

How can molecular biological techniques help with studying genetics?

Answer 21

• Use of restriction enzymes to cleave DNA at particular points to isolate genes
• PCR to amplify certain DNA sequences
• DNA sequencing to identify the order of nucleotides
• Genetic sequencing used for cancer risk prediction

Question 22

How can genes confer pathogen virulence?

Specific examples related to specific pathogens

Answer 22

• Use of reverse transcriptase by HIV to aid with integration into the human genome
• Bacteria using plasmids to exchange genetic material e.g. antimicrobial resistance
• Genes that enable rapid exchange of surface antigen e.g. Influenza A has this

Question 23

How can molecular biological techniques aid with pathogen identification?

Answer 23

• Identifying a causative organism where there are multiple possible causes e.g. meningitis
• Identifying which strain of the pathogen has caused disease where there are differences in severity and medication susceptibility between strains e.g. Hep C
• Discovering new pathogens
• Detecting trends in strains of new disease
• Linkage of infectious disease to identify/investigate outbreaks