Genetics

Question 1

Familial risks

Answer 1

What is the incidence of a disorder in relatives compared to the incidence in the general population?

Question 2

Twin studies

Answer 2

What is the incidence in monozygotic compared to dizygotic twins?

Question 3

Adoption studies

Answer 3

What is the incidence in adopted children of the disorders which their parent had?

Question 4

Population and migration studies

Answer 4

What is the incidence in people from a particular ancestry group when they move to a different geographical area?

Question 5

Huntingdon’s disease

Answer 5

• Autosomal dominant disease with high penetrance

Question 6

Huntingdon’s features

Answer 6

• Progressive degenerative disorder of the CNS - dementia, movement disorder, personality changes
• Incurable, treatment for symptoms only
• Mutations due to CAG repeat expansion

Question 7

Huntingdon’s Peak age of onset

Answer 7

40 years

Question 8

Huntingdon’s transmission

Answer 8

Vertical transmission

Question 9

Anticipation

Answer 9

Age of onset can decrease with generations

Question 10

Huntingdon’s aetiology

Answer 10

11 - 34 CAG repeats are normal –> encodes run of 11 - 34 glutamine amino acid residues in the protein
A run of > 35 glutamine residues causes the protein to aggregate in the brain cells –> progressive cell death
>35 CAG repeats in the gene expand further (esp in male meiosis) –> earlier age of onset in children of affected men - anticipation
Toxic-gain-of-function genotype

Question 11

Penetrance

Answer 11

the chance that a genotype results in the associated phenotype

Question 12

Hereditary Haemochromatosis

Answer 12

Autosomal recessive condition characterised by iron overload

Question 13

Hereditary Haemochromatosis aetiology

Answer 13

Due to mutations of HFE gene –> missense mutations, single nucleotide polymorphisms, point mutations
–> change in amino acid - specifying codon
Recessive diseases are usually assoc w/ mutations that cause loss-of-normal-protein function

Question 14

Hereditary Haemochromatosis Presentation

Answer 14

Life threatening disease associated with high morbidity and mortality
Iron overload –> organ damage
- Regular venesection provides an effective treatment - quantitative reduction in iron stores

Question 15

Expressivity

Answer 15

Degree to which the range of signs/symptoms for a given trait differ between individuals

Question 16

Pleitropy

Answer 16

mutations in a single gene can influence multiple phenotypic traits

Question 17

Polygenic inheritance

Answer 17

the inheritance and expression of a phenotype being determined from many genes at different loci (small additive effects)

Question 18

Multifactorial disorders

Answer 18

Require interaction of environment and genetic factors to manifest

Question 19

Proband

Answer 19

1st individual in investigation of related patients with an inherited disorder

Question 20

The genome

Answer 20

3 million base pairs
Packaged in chromosomes
~ 21,000 protein coding genes
alternate gene splicing
Non-coding RNAs

Question 21

Tandem repeat

Answer 21

• short sequences of DNA repeated in head to tail fashion
• mini/micro satellites
• variable number of tandem repeats are very polymorphic

Question 22

Polymorphism

Answer 22

A variant that is common enough to affect more than 1% of chromosomes in a given population

Question 23

Human Genome Project

Answer 23

1990 - 2003
Mapping variation and functional effects
3 Billion base pairs + 21,000 coding genes

Question 24

Types of SNV/SNP in coding DNA

Answer 24

Silent mutation
Stop codon
Missense (diff amino acid created)

Question 25

Pharmacogenetics

Answer 25

Studying individual variants to predict response to medicine or to guide prescribing

Question 26

Pharmacogenomics

Answer 26

Analysing genome-wide variants in an individual or a population to identify markers that predict response

Question 27

Meitotic nondisjunction

Answer 27

Failure of tow members of a chromosome pair to separate from one another during meiosis --> both chromosomes go to a single daughter cell

Question 28

Patau's Syndreom

Answer 28

Trisomy 13 | - Mental retardation, growth failure, low-set ears, deafness, microcephaly, cleft lip and palate, septal defects

Question 29

Edward's Syndrome

Answer 29

Trisomy 18 - V. small head, back of head prominent, malformed ears, small mouth and jaw, hands clenched into fists, clubfeet, webbed toes

Question 30

Down's Syndrome

Answer 30

Trisomy 21 - Broad, flat face, epicanthic eyefold, short nose, short and broad hands, small and arched pa;ate, growth failure, mental retardation

Question 31

Turner's Syndrome

Answer 31

Monosomy X Short stature, low hair line, webbed neck, constriction of aorta, undeveloped breasts, shield-shaped thorax, elbow deformity

Question 32

Aneuploidy

Answer 32

when an organism gains/loses a chromosome | --> occurs during meiosis/mitosis, usually non-disjunction

Question 33

Risk factors for aneuploidy

Answer 33

Increasing maternal age, maternal hypothyroidism, irradiation, viral infection, familial tendency

Question 34

Splicing mutation

Answer 34

Sequence that guides introns from mRNA are mutated - abnormal splicing. Translated protein may carry intron sequences --? alterd amino acids incorporated into polypeptide chain

Question 35

DNA Primary Structure

Answer 35

Chains of nucleotides held by phosphodiester bonds attaching the phosphates

Question 36

DNA Secondary Structure

Answer 36

2 DNA strands held together by H bonds between complimentary base pairs

Question 37

DNA Tertiary Structure

Answer 37

Packaging - DNA is wrapped around histones, forming chromatin. Chromatin is packed into nucleosomes and then supercoiled into a chromasome

Question 38

3 types of RNA in eukaryotic cells

Answer 38

mRNA - messenger tRNA - transfer rRNA - ribosomal

Question 39

Messenger RNA

Answer 39

copied from DNA and used as template for protein synthesis

Question 40

Transfer RNA

Answer 40

small molecules which transfer amino acids to the ribosomes for protein synthesis

Question 41

Ribosomal RNA

Answer 41

involved in binding mRNA and tRNA during protein synthesis

Question 42

In RNA which nitrogen base has changed

Answer 42

thymine --> uracil