Genetics

Question 1

When does DNA replication occur?

Answer 1

During S - Synthesis phase

Question 2

Mutation?

Answer 2

May or may not cause a disease

Question 3

What is an acrocentric chromosome?

Answer 3

A chromosome in which the centromere is located quite near one end. They are number 13, 14, 15, 21 and 22

Question 4

Aneuploidy vs Translocation

Answer 4

Aneuploidy is an extra or missing chromosome

Translocation is rearrangement of chromosome

Question 5

What causes Down Syndrome

Answer 5

Extra chromosome 21, acrocentric chromosome

Question 6

What is Robertsonian translocation?

Answer 6

Two acrocentric chromosomes stuck end to end

Question 7

Edwards Syndrome

Answer 7

Trisomy 18

Small head, clenched fist, cleft lip or palate, toes may be clubbed or fused

Question 8

Causes of the following -
Turners Syndrome
Triple X
Klinefelter Syndrome

Answer 8

Turners Syndrome - 45 X
Triple X - 47 XXX
Klinefelter Syndrome - 47 XXY

Question 9

Which translocations have no effect on phenotype

Answer 9

Balanced translocations

Question 10

What can large unbalanced dislocations result in?

Answer 10

Miscarriage

Question 11

What is FISH used for

Answer 11

FISH - Florescent in Situ Hybridisation is used to detect and localize the presence or absence of specific DNA sequences on chromosomes

Question 12

Microarray CGH

Answer 12

Array Comparative Genomic Hybridisation (aCGH)
Detects missing or duplicated chromosomes
However, many changes seen might be polymorphisms

Question 13

What is mosaicism

Answer 13

Different individual cells have different genetic constitution

Question 14

Polymerase Chain Reaction

Answer 14

Allows us to select one small piece of human genome and amplify it

Question 15

Example of an enzyme used in PCR

Answer 15

Heat - resistant Taq Polymerase

Question 16

What is missense mutation?

Answer 16

Type of point mutation in which a single nucleotide change results in a codon that codes for a different amino acid

Question 17

What is post zygotic mutation

Answer 17

Mutation that occurs in the embryo

Question 18

What is penetrance

Answer 18

The likelihood of having a disease if you have a genetic mutation

Question 19

What is Achondroplasia caused by?

Answer 19

Achondroplasia is caused by a mutation in Fibroblast Growth Factor Receptor 3 (FGFR3)

Question 20

Salient feature of autosomal dominant

Answer 20

Every generation is affected, 50% risk for children

Question 21

Salient feature of autosomal recessive

Answer 21

Only one generation affected, 25% chance

Question 22

X linked recessive inheritance

Answer 22

Carrier father, female offspring always carrier
Passes from female carrier to affected male to female
No male to male transmission

Question 23

What are copy number variants

Answer 23

Sections of the genome are repeated and the number of repeats in the genome varies

Question 24

What is the common disease - common variant hypothesis

Answer 24

Thecommon disease-common varianthypothesis predicts that common disease-causingalleles, orvariants, will be found in all human populations which manifest a given disease. However these traits are neutral because many genes influence a trait

Question 25

How do we know there is a genetic contribution to disease

Answer 25

If the disease is more prevalent or higher risk in first degree relatives

Question 26

Which parents passes on mitochondrial DNA

Answer 26

Mother

Question 27

What is heteroplasmy

Answer 27

A cell can have some mutation in mitochondrial DNA and some that do not

Question 28

Weinberg hallmarks of cancer

Answer 28

``` Evade apoptosis Self-sufficiency in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiongenesis ```

Question 29

What are driver mutations

Answer 29

Mutations that drive carcinogenesis

Question 30

What are passenger mutations

Answer 30

Incidental mutations that happen because tumour is unstable

Question 31

What determines cancer characteristics, driver mutation or tissue of origin

Answer 31

Driver mutation

Question 32

All cancer cells have the same genetic makeup

Answer 32

False, most cancer cells are genomically unstable and have different genetic makeup

Question 33

What can be used for treatment of late stage melanoma

Answer 33

Vemurafenib

Question 34

Significance of HER2

Answer 34

Human epidermal growth factor receptor play an important role in development and progression of certain types of breast cancer. HER2 protein is an important biomarker and target of therapy

Question 35

Monoclonal antibody used to treat breast cancer

Answer 35

Trastuzumab (Herceptin), especially HER2 receptor positive

Question 36

What is the Philadelphia chromosome or Philadelphia translocation

Answer 36

Translocation of genetic material between chromosome 9 and 22. ABL-1 gene of 9 onto BRC gene of 22 coding for a tyrosine kinase causing the cell to divide uncontrollably.

Question 37

What can be used to treat leukemia that are Philadelphia chromosome positive and certain GI stromal tumours

Answer 37

Imatinib (Glivec)

Question 38

What is a mutator gene

Answer 38

A gene that increases the rate of mutation of one or more genes

Question 39

What are mismatch repair genes (MMR)

Answer 39

Genes that code for proteins capable of mechanisms to repair errors in repeat units of microsatellites. Errors in these can lead to genomic instability causing mutations

Question 40

How many % of women get breast cancer

Answer 40

Around 10%

Question 41

What can mutation in BRCA 1 lead to

Answer 41

Familial breast cancer

Question 42

What is symptomatic testing

Answer 42

Always test a symptomatic person first. If we identify a mutation in the parent we can offer the offspring a pre-symptomatic test

Question 43

Estimate the risk for daughter if mother with breast cancer at 70

Answer 43

Low risk

Question 44

Estimate the risk for daughter if mother and sister with breast cancer at 45

Answer 44

Medium risk

Question 45

Estimate the risk for daughter with BRCA-1 mutation

Answer 45

Low risk

Question 46

Drug used to treat pre and post menopausal women

Answer 46

Tamoxifen

Question 47

Screening for breast cancer

Answer 47

Mammography, breast examination

Question 48

Surgical intervention for breast cancer

Answer 48

Mastectomy and Oophorectomy

Question 49

Common disease - Common variant hypothesis

Answer 49

States common disease causing alleles or variants will be found in most of the population. Some of these variants lead to susceptibility to polygenic disease as each variant at each gene influences a disease by having additive effects on the disease phenotype. However, many genes influence a trait and these variants are neutral in part

Question 50

Common features of Mendelian disorders

Answer 50

Scary family history, young age, more people affected. These need to be identified whereas common disorders need to have risk estimated.

Question 51

How does symptomatic testing work

Answer 51

Genetic test the diseased family member. If mutation is found, we can confirm our diagnosis. Can also test other family members as part of presymptomatic testing. If no mutation found, treat on clinical parameters

Question 52

What is presymptomatic testing

Answer 52

Testing a patient who has a relative with a known mutation. If mutation is found, confirms patient will develop the disease.

Question 53

What is the Wolf-Hirschhorn Syndrome

Answer 53

Partial deletion of short arm of chromosome 4. Results in characteristic facial appearance, delayed growth, intellectual disability and seizures

Question 54

Huntington's disease cause

Answer 54

CAG repeat encoding Poly-Glutamine. This has toxic effect on cells, neuronal loss

Question 55

The more CAG repeats you have, higher chances of developing Huntington's early on

Answer 55

True

Question 56

How can genetic testing affect families negatively

Answer 56

Real implication for other family members, family/social issues, adoptions, family feuds