Genetics 5, 6, 7 - Modes of inheritance, cancer and clinical practice

Question 1

What are the 4 non-mendelian modes of inheritance?

Answer 1

MultifactorialiMprinting (epigenetic modification of DNA)MitochondrialMosaicism

Question 2

What are copy number variations? (CNV)

Answer 2

Extra or missing stretches of DNA

Question 3

Penetrance of genetics in a mendelian disorder?

Answer 3

High

Question 4

Pentrance of genetics in a multifactorial disease?

Answer 4

Genetic change is just another risk factor, therefore penetrance is low for any one mutation

Question 5

How many genes do monozygotic and dizygotic twins share?

Answer 5

Monozygotic = allDizygotic = 50%

Question 6

What does P

Answer 6

There is a 1 in 20 probability that the data you see has happened by chance

Question 7

What are risk models?

Answer 7

Any equation that ties together different risk factors and gives you a risk prediction for your patient

Question 8

What is epigenetic modification of DNA/ imprinting?

Answer 8

When only one working allele is inherited (either mum or dad allele has been silenced) due to heritable alterations that are not due to changes in DNA sequence. Rather, epigenetic modifications, or tags, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression.

Question 9

What is DNA methylation?

Answer 9

an epigenetic mechanism that occurs by the addition of a methyl (CH3) group to DNA, thereby often modifying the function of the genes

Question 10

What is the name for DNA complexed with histones?

Answer 10

Nucleosomes

Question 11

Difference between chromosomes, chromatin and chromatids?

Answer 11

Chromatin = double-stranded helical structure of DNANucleosome = DNA complexed with histonesChromataosome = nucleosome + H1 proteinChromosome = tightly coiled nucleososmes - made up of chromatid

Question 12

Where does methylation of DNA usually occur?

Answer 12

On cytosine bases just before guanine bases

Question 13

What does DNA methylation cause?

Answer 13

Modification of histones repressing transcription

Question 14

What is an example of a disease that can occur due to abnormalities of methylation?

Answer 14

Cancer (methylation causes gene silencing - histone de-acetylation is a drug target)

Question 15

What is an example by how environment affects methylation?

Answer 15

Starvation during pregnancy affects foetus - methylation allows your environment to affect your genome

Question 16

How can methylation affect behaviour?

Answer 16

RETT syndrome - changes methylation pattern of the genes in brain to the point were certain functions of the brain stop working

Question 17

What are the symptoms of angelman syndrome?

Answer 17

Neurogenetic disorder causing developmental delay, intellectual disability, ataxia, epilepsy, happy demeanour, frequent laughing and smiling

Question 18

What causes Angelman’s syndrome?

Answer 18

Not having the working copy of the UBE3A gene on chromosome 15It only works in the mother’s copy - fathers copy is methylated

Question 19

What does methyl cytosine mutate easily to?

Answer 19

Thymine

Question 20

Apart from in the nucleus, where else is DNA kept in humans?

Answer 20

Mitochondria

Question 21

What is heteroplasmy?

Answer 21

Different daughter cells contain different proportions of mutant mitochondria

Question 22

What are symptoms of mitochondrial disease?

Answer 22

MyopathyDiabetesDeafnessOptic atrophyStroke like episodesEncephalitis(dependant on mutation type and level of heteroplasty in different tissues)

Question 23

Are daughters affected more in mitochondria inheritance?

Answer 23

No - sons and daughters are affected equally

Question 24

What are the 4 ways in which DNA can be damaged?

Answer 24

Inherited mutationsDNA strand breaksMistakes in DNA synthesisChemical damage e.g. UV, smoking

Question 25

What are the main mechanisms by which genes are activated? (3)

Answer 25

Duplication of the geneActivation of the gene promotorChange in amino acid sequence

Question 26

What is the fate of a cell that has accumulated DNA damage? (4)

Answer 26

RepairSenescenece (cessation of cell growth of potentially cancerous cells)ApoptosisTumour growth

Question 27

Mechanisms of DNA repair?

Answer 27

Direct repairBase excisionNucleotide excisionMis-match repair complex

Question 28

What is mis-match repair?

Answer 28

Mis-mathc e.g. A-C is recognised and excised by mis-mathc repair complex

Question 29

What is an example of a condition caused by a mutation in a mis-match repair gene?

Answer 29

Hereditary non-polyposis colorectal cancer

Question 30

What do BRCA1/2 carriers have in terms of cancer risk?

Answer 30

An 80% chance of developing breast or ovarian cancer

Question 31

What is a drug that can be used to prevent breast cancer?

Answer 31

Tamoxifen

Question 32

What’s huntingtons disease?

Answer 32

An inherited condition that damages certain nerve cells in the brain

Question 33

Applications of genetic testing to bacteriology?

Answer 33

You can characterise bacteria by their DNA sequence more effectively than growing them on a plate (same with tumours in the very near future)