GiM week 1

Question 1

What is pseudohypoaldosteronism an example of?

Answer 1

rare genetic disease that causes hypotension

Question 2

what is liddle’s syndrome an example of?

Answer 2

rare genetic disorder that causes hypertension

Question 3

what 3 types of tests could you do for genetic disorders?

Answer 3

blood tests (enzyme assays or haematology)

x-rays (checking for skeletal dysplasia)

genetic tests

Question 4

what is an example of an inherited skeletal dysplasia?

Answer 4

achondroplasia

Question 5

what 5 different types of genetic tests can you do?

Answer 5

genomic architecture:

• cytogenetics
• array based techniques

gene faults

• sequencing
• OLA assays
• MLPA tests

Question 6

what is pharmacogenomics?

Answer 6

analysing entire genomes, across groups of individuals, to identify the genetic factors influencing responses to a drug

Question 7

what is pharmacogenetics?

Answer 7

studying an individual’s genetic make up in order to predict responses to a drug and guide prescription

Question 8

what is gleevec?

Answer 8

a treatment for Chronic Myeloid Leukaemia (CML)

it targets the novel fusion protein, the product of the translocation seen in CML

(works on a somatic mutation, not germ line!)

Question 9

what is CADASIL?

Answer 9

Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

• most common form of hereditary stroke disorder

Question 10

what are the 5 types of genetic disorders?

Answer 10

• multifactorial/complex
• single gene
• chromosomal
• mitochondrial
• somatic (cancer)

Question 11

what do dominant genetic conditions tend to affect?

Answer 11

structural proteins

Question 12

what do recessive genetic conditions tend to affect?

Answer 12

metabolic proteins

Question 13

what type of inheritance do almost all chromosomal disorders show?

Answer 13

dominant

Question 14

what are 3 examples of dominantly inherited disorders?

Answer 14

• myotonic dystrophy
• hunting tons disease
• marfan syndrome

Question 15

what does penetrance mean?

Answer 15

the frequency with which a specific genotype is expressed by those individuals that possess it (usually given as a percentage)

(eg huntingtons has 100% penetrance, BRCA1 mutation has 80% penetrance)

Question 16

what does expressivity mean?

Answer 16

variation in expression of a genetic disease
- the extent to which a heritable trait is manifested by an individual

(eg in marfan syndrome, an individual could have aortic dilatation OR lens dislocation OR BOTH)

Question 17

what does anticipation mean?

Answer 17

the symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next

in most cases there is an increase in the severity of symptoms too

(to do with triplet expansion)

Question 18

if both parents have a particular autosomal recessive condition, what is the risk that an unaffected child will be a carrier?

Answer 18

2 in 3

1 will be affected, 2 will be carriers and 1 will be normal

Question 19

name some common autosomal recessive conditions

Answer 19

• cystic fibrosis
• haemachromatosis (excess absorption of iron)
• sickle cell disease

many of the metabolic disorders

Question 20

can you have father to son transmission in X-linked conditions?

Answer 20

no

Question 21

what two main factors influence the expression of the phenotype in ‘carrier’ women of X-linked conditions?

Answer 21

• X inactivation

- whether it is a X-linked dominant or X-linked recessive condition

Question 22

what is X-inactivation and what is it also known as?

Answer 22

aka lyonisation

the normal process of random inactivation of one of the X chromosomes in cells with more than one X chromosome

(compensates for the presence of the double X gene dose)

occurs in early embryogenesis, once inactivated an X-chromosome remains inactive throughout the lifetime of the cell and all its descendants

it is random as to which X is silenced
- most, but not all, genes switched off on the inactivated X

Question 23

how does X-inactivation in X-linked recessive conditions in females affect the phenotype?

Answer 23

approximately 50% of cells express the normal gene
- however if there is SKEWED INACTIVATION then either more, or less, of the ‘normal’ gene could be switched on

if more normal switched on = milder phenotype
if more mutated switched on = more severe phenotype

also there may be TISSUE VARIABILITY
- random preference for the mutation to be active in any given tissue group, if turned on more in a crucial tissue group (e.g. muscles for muscular dystrophy) when stronger phenotype

Question 24

name two X-linked dominant conditions

Answer 24

• Rett syndrome = learning disabilities (lethal in males, phenotype only in females)
• fragile X-syndrome = learning disabilities and autism (asymptomatic to fully symptomatic, depending on X-inactivation)

Question 25

name 2 mitochondrial inherited diseases

Answer 25

• maternally inherited diabetes

- maternally inherited deafness

Question 26

on a family pedigree, how do you indicate:

1) a therapeutic abortion
2) a spontaneous abortion (miscarriage)
3) a stillborn baby of unknown sex

Answer 26

1) small triangle with line through
2) small triangle
3) diamond with line through, with SB next to it

Question 27

how do you indicate that someone is an asymptomatic carrier of a disease?

Answer 27

put a coloured dot in the centre of the symbol

Question 28

what method is used to detect a fragile X mutation?

Answer 28

southern blotting

Question 29

the fragile X mutation occurs in a tract of sequence which is…..

Answer 29

repetitive

Question 30

a mutation in which gene results in microcephaly?

Answer 30

ASPM gene

Question 31

a mutation in which gene can increase the likelihood of developing leukaemia?

and what is the name given to the chromosome this mutation is found on?

Answer 31

BCR/abl fusion gene

philadelphia chromosome

Question 32

Which drug can non-small cell lung cancers which harbour EGFR/HER1 mutations be treated with?

Answer 32

gefitinib

Question 33

As most amino acids have more than one possible three letter base code, the code is said to be….

Answer 33

degenerate

Question 34

In the nomenclature for DNA, the symbol ′ as used in 5′ stands for….

Answer 34

prime

Question 35

what type of mutation results in the substitution of one amino-acid residue for another?

Answer 35

missense mutation

Question 36

what type of mutation results in a truncated protein?

Answer 36

nonsense mutation (due to a premature stop codon being coded for)

Question 37

the diploid human genome consists of two sets of chromosomes which are….

Answer 37

homologous

Question 38

what does CNV stand for?

Answer 38

copy number variation

Question 39

how many protein coding genes are there in the human genome?

Answer 39

20,000

Question 40

The Alu repeat is an example of what type of repeat?

Answer 40

interspersed repeat

specifically they are SINEs:
Short Interspersed Nuclear Elements: short DNA sequences (<500 bases) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase III

Question 41

what is PCR?

Answer 41

polymerase chain reaction

in vitro synthesis of large amounts of dan by copying from small starting quantities

products of PCR then separated (on basis of size) by gel electrophoresis, stained DNA is then visualised using UV light

Question 42

what is OLA?

Answer 42

Oligonucleotide Ligation Assay

• A test for detecting KNOWN SNPs
• more specific than PCR but only works with known mutation
• involves using a patients DNA compared to a ‘normal’ control DNA, then try and get ligation to occur, (you find out if it has using gel electrophoresis) if it doesn’t: the patient has the mutation being tested for
  (ASK FOR HELP WITH THIS! - NOT SURE IF CORRECT!!)

Question 43

what is FISH?

Answer 43

Flourescence in situ hybridisation

ASK FOR HELP WITH THIS! - DON’T UNDERSTAND!!