Genetics

Question 1

What is the biggest cause of trisomies?

Answer 1

Maternal Dis-junction - failure of normal chromosomal separation

Question 2

What is Trisomy 13? and name some symptoms:

Answer 2

Patau Syndrome

congenital heart disease - 50% die before 1 month

Question 3

What is trisomy 18?

Answer 3

Edward’s syndrome

Question 4

What kind of tumor suppressor is the BRCA gene?

Answer 4

Stability Gene

Question 5

What is the main function of BRCA genes?

Answer 5

To code for homologous DNA repair for double stranded breaks

Question 6

What two less common genes are associated with breast and ovarian cancer?

Answer 6

MLH1

MLH2

Question 7

What is a prophylactic drug being used to treat ovarian cancer?

Answer 7

Aloparib

Question 8

Hereditary Non - polyposis Colon cancer is most commonly caused by which genes?

Answer 8

MLH1

MSH2

Question 9

Familial Adenomatous Polyposis is most commonly caused by which genes?

Answer 9

APC gene on chromosome 5.

Question 10

What non -clinically significant symptom may a patient with familial adenomatous polyposis have?

Answer 10

Congenital hypertrophy of the retinal pigmented epithelium

Question 11

Name a autosomal recessive cancer:

Answer 11

MYH Polyposis

Question 12

What does the MYH gene code for?

Answer 12

Base excession repair

Question 13

In Huntington’s disease, which gene is affected and what is the cause of pathology?

Answer 13

HHT gene.

CAG repeats - glutamine build up n the protein leading to aggregates forming.

Question 14

Defects in DMPK gene will cause which disease?

Answer 14

Myotonic dystrophy

Question 15

In myotonic dystrophy, what gene is affected and how does this cause pathology?

Answer 15

DMPK gene.

3’ CTG repeats - causing faulty DMPK mRNA.
This indirectly causes toxic affect on the splicing of other mRNA.

Question 16

Name an important mRNA that is indirectly affected by DMPK -causing characteristic myotonia

Answer 16

CLCN-1 mRNA

Question 17

What is the most common gene mutation in CF?

Answer 17

F508 deletion

Question 18

What protein does DMD code for?

Answer 18

Dystrophin - an intracellular protein that attaches to the dystroglycoprotein complex and the actin filament - communicating with extracellular of cell

Question 19

Whats the most common mutation in DMD and what does this cause that leads to such severe symptoms being seen?

Answer 19

Deletion of exons in the DMD gene, causing frame shifting, causing complete protein dysregulation .

Question 20

Whats implicated in FMR1 gene?

Answer 20

Fragile X - syndrome

Question 21

How is Fragile X syndrome developed?

Answer 21

tri-nucleotide repeats at the 5’ end of FMR1 gene.

resulting in silencing of the gene - through methylisation

Question 22

What type of sequencing would be done to search for a point mutation in an unknown gene defect?

Answer 22

Sangers sequencing

Question 23

What type of sequencing is done for a point mutation of known allele? i.e. the mutation is known.

Answer 23

ARMS sequencing

Question 24

What time of testing is done for a sub-microscopic mutation, where the gene allele is not known? and how is it interrupted?

Answer 24

aCGH

Green: duplication
Red: deletions

Question 25

What type of testing is done for a sub-microscopic mutation, where the gene allele is known?

Answer 25

MLPA

Question 26

With regards to genetic testing what does PGD mean and what are some pros and cons?

Answer 26

Pre- implantation diagnosis Pros: - allows implantation of unaffect cells Cons: - Not available to all women - long wait - 50% take home baby rate

Question 27

What are polyploidies? and give an example:

Answer 27

Abnormal number of chromosomes in a multiple of 23. Triploidy: 69 chromosomes this can occur in hydatidiform changes, where 2 sperm penetrate an egg, resulting in 69 chromosomes.

Question 28

What syndrome can FISH be useful for identifying?

Answer 28

Williams Syndrome

Question 29

Name some neonatal screening tests carried out Mass spectrometery:

Answer 29

PKU MCADD

Question 30

Name the set of conditions that show genetic anticipation:

Answer 30

Huntington's Myotonic dystrophy Fragile X syndrome (to a degree)

Question 31

What drug re-opens the Cl- channel in CF, which is a type of precision medicine? what is the mutation it specifically works on?

Answer 31

Ivacaftor G551D

Question 32

What gene has been cut out using CRISPR CAS9 and what disease does it cause?

Answer 32

FBN1 - marfan's syndrome

Question 33

Which drug targets the HER2 - EGFR2 receptor?

Answer 33

Trastuzumab

Question 34

The new therapy proposed for DMD is what?

Answer 34

Antisense oligonucleotide therapy - causes exon skipping to create an inframe mutations - less severe than normal DMD out of frame mutations.

Question 35

Name some autosomal recessive conditions:

Answer 35

Cystic Fibrosis PKU Spinal Muscular Atrophy Congenital adrenal hypoplasia

Question 36

In an X-linked recessive condition, what would you expect the disruption to be amongst males and females from a female carrier?

Answer 36

50% daughters carriers 50% sons affected

Question 37

Name some X-linked dominant conditions:

Answer 37

Vit D deficiency Rett syndrome Incontinentia pigmenti

Question 38

In which type of pattern of inheritance would you expect to see higher rates of females affected?

Answer 38

X-linked dominant

Question 39

What is the disease, that is a mitochondrial disease leading to lack of ATP synthesis, and what is the gene?

Answer 39

Leigh's disease MT-ATP6 gene

Question 40

Which chromosome is HER2 gene found on? and what is a good analysis tool for looking at it?

Answer 40

chromosome 17 FISH

Question 41

Which disease shows genetic anticipation if the mother is a carrier?

Answer 41

Myotonic dystrophy

Question 42

What is some of the symptoms of neurofibromatosis?

Answer 42

Cafe au lait macules neurofibromas 30% having learning difficulties

Question 43

List the trinucleotide repeat disease:

Answer 43

Huntington's - CAG - glutamine - anticipation from father - AutoD Mytonic Dystrophy - CTG - Anticipation from mother - AutoD Fragile X - CCG - anticipation - x-linked

Question 44

What's the blood markers carried out for carriers and children who have duchene muscular dystrophy?

Answer 44

Serum Creatinase Kinase

Question 45

What's the sign called when a child has to use their hands on their knees to push themself up?

Answer 45

Gowen's sign

Question 46

List some comparisons between autosomal dominant and autosomal recessive conditions:

Answer 46

Vertical vs Horizontal Homozygous vs heterozygous 50% vs relatively low risk depending on population risk Variable expression vs Constant expression Incomplete penetrance vs Complete penetrance

Question 47

Define what a Point mutation is:

Answer 47

Single change in the nucleotide sequence

Question 48

Define what a missense mutation is:

Answer 48

Point mutation in which the single nucleotide change results in codon that codes for a different amino acid.

Question 49

Define what a silent point mutation is:

Answer 49

Where the single nucleotide change codes for the same amino acid

Question 50

What is a conservative point mutation?

Answer 50

Where a point mutation leads to a different amino acid being produced, but is very similar to original amino acid.

Question 51

Define what a Nonsense mutation is?

Answer 51

Were a premature stop codon is formed - causing premature termination of protein synthesis.

Question 52

What is the symptoms of fragile x syndrome?

Answer 52

It is the most common cause of mendelian inheritance to cause mental impairment ``` Low IQ Inverted ears Mitral prolapse long facial features enlarged testicles ```

Question 53

Variable expression may occur in AS dominant conditions, what is it that causes this?

Answer 53

Variable expression is where there is different severities of the disease. It may be caused by: - stability genes - epigenetics

Question 54

How is Cystic fibrosis screened for?

Answer 54

Immunoassay Cl- levels in sweat of the baby. If these are positive then DNA testing is done.

Question 55

If a person has myotonic dystrophy, they are at greater risk of developing another disease, what is this and why?

Answer 55

Diabetes and this is because of damage to the mRNA that codes for the insulin

Question 56

What is a very good test for detecting gene deletions?

Answer 56

MLPA | *the area must be known

Question 57

What is a very good test for detecting trisomy?

Answer 57

QF - PCR

Question 58

Mutated Proto-oncogenes are usually not inherited, name one that is and what it is associated with:

Answer 58

RET MEN2 - pheochromocytoma

Question 59

What area on the x chromosome is dystrophin coded, and thus is mutated in DMD patients?

Answer 59

Xp21

Question 60

What drug is good for stopping colorectal cancer?

Answer 60

Aspirin

Question 61

What serious trisomy is associated with an extra little finger?

Answer 61

Patau syndrome - trisomy of 13