Genetics

Question 1

Which two syndromes are associated with a cherry red macula?
(Hint: they both have also developmental regression)

Answer 1

Neimann Pick Type 1 OR Tay Sachs disease
Tay Sachs disease is a lysosomal storage disorder that presents after 3 months with regression of gross motor skills. Macrocephaly is common because of accumulation of GM2 ganglioside in the brain. Niemann Pick Disease Type A is also associated with developmental regression and a cherry red macula but reflexes are absent or reduced. Macrocephaly is not a usual feature.

Question 2

What are the 4 base pairs in DNA and what is the pairing?

Answer 2

Adenine
Thymine
Cytosine
Guanine
A-t, C-G

Question 3

How many hydrogen bonds between G and C?

Answer 3

3

Question 4

What percentage of the genome is protein encoding genes?

Answer 4

1-2% are exons

Question 5

How many base pairs in the genome?

Answer 5

3 billion

Question 6

What are the 4 phases of Miosis?

Answer 6

Prophase- duplication of chromosomes
Metaphase- chromosomes align at central plate
Anaphase: sister chromatids separate
Telophase: separate into 2 cells

Question 7

What happens in Prophase 1?

Answer 7

Chromosomal duplication AND binding of homologous chromosomes to form tetrameres

Question 8

What happens in Metaphase 1?

Answer 8

Tetrads align in the centre.

Question 9

What happens in telo and anaphase 1?

Answer 9

Homologous chromosomes are separated, but sister chromatids remain together.

Question 10

What happens in meiosis II?

Answer 10

Sister chromatids separate so there is HALF the number of chromsomes now in the daughter cells vs parent cells

Question 11

What is the result of chromosomal non disjunction?

Answer 11

Aneuploidy. Essentially, the chromosomes dont separate so get one egg with 2 chromsomes and one with none.

Question 12

What is the role of helicase, ligase and DNA polymerase?

Answer 12

Helicase unzips DNA
Ligase fills in gaps
Polymerase copies- 5’ to 3’ in leading and other way around in lagging strand

Question 13

Where are promoter regions?

Answer 13

Upstream at 5’ end of the first exon, often contains TATA box

Question 14

Where are enhancer or silencor regions?

Answer 14

Can be anywhere, further modify expression

Question 15

What are the 3 consequences of a base substitution?

Answer 15

Silent/synonymous mutation
Nonsense: premature stop codon
Missense: change in amino acid

Question 16

What is the conseuqence of deletions and insertions?

Answer 16

Alter reading frame, resulting in completely diff sequence of amino acid

Question 17

What is the difference between penetrance and expressivity?

Answer 17

Penetrance is if you have he phenotype or not,
Expressively is HOW much of the phenotype you have.

Question 18

What is the baseline risk of having an autosomal recessive condition/ a syndrome?

Answer 18

3%

Question 19

What is the risk of a serious syndrome/recessive condition in consanguineous marraiges?

Answer 19

Double, 6%

Question 20

Why is it clinically important to check the genetic cause of T21?

Answer 20

Unbalanced trans location between 4:21 means that there is extra 21 chromosome and one of the parents can be a carrier, pass onto next child

Question 21

What are 5 features of Klienfelters?

Answer 21

hypogonadism, low testosterone, infertility, incomplete virilisation, gynaecomastia, tall stature, mild learning disabilities, emotioanlly immature, shy

Question 22

What is the number one cause of male hypogonadism?

Answer 22

Klienfelters

Question 23

What are the main features of Turners?

Answer 23

Webbed neck, infertility, short stature, NORMAL inellect

Question 24

What are the cardiovascular defects associated with Turners?

Answer 24

Coarctation of aorta, bicuspid aortic valve

Question 25

What is an example of a condition that has issues with copy number variants?

Answer 25

Retts

Question 26

What is the carrier risk in a sibling of an individual WITH a recessive condition?

Answer 26

2/3

Question 27

Name 2 X linked dominant conditions

Answer 27

X linked hypophosphataemic rickets, incontinentia pigmenti

Question 28

What is anticipation in the context of genetics and triplet repeat disorders?

Answer 28

Phenotype worsens in subsequent generations as you inherit more and more triplet repeats

Question 29

What is the risk of atopy in child if parent has it?

Answer 29

50%. This increases to 66% if both parents have it or if two first degree relatives have

Question 30

What are contigous gene syndromes?

Answer 30

group of disorders in which a small deletion or duplication of genetic material that contains multiple genes causes a recognizable phenotype. ie Prader-Willi syndrome (PWS), Angelman syndrome (AS), and Williams syndrome (WS). Another disorder, 22q11.2 deletion syndrome

Question 31

What are contigous gene syndromes?

Answer 31

group of disorders in which a small deletion or duplication of genetic material that contains multiple genes causes a recognizable phenotype. ie Prader-Willi syndrome (PWS), Angelman syndrome (AS), and Williams syndrome (WS). Another disorder, 22q1What1.2 deletion syndrome

Question 32

What is a good diagnostic test for Smith Lemli Opitz syndrome?

Answer 32

7-dehydrocholesterol

Question 33

What is the minimum number of repeats req to display Fragile X?

Answer 33

>200 between 55-200 is asymtpmatic, premutation carriers

Question 34

What is epigenetics?

Answer 34

Change in how DNA is read, NOT actual change to the DNA

Question 35

What is the gene/locus affected for Prader Willi and Angelman?

Answer 35

15q11.2-q13

Question 36

What is imprinted in Prader-Willi Syndrome?

Answer 36

Paternal Imprinting. P for PATERNAL (Remember Angelman and Prada linked, Angel wears Prada which is 15x more expensive that silver)

Question 37

What is imprinted in Angelman syndrome?

Answer 37

Maternal imprinting (Remember Angelman and Prada linked, Angel wears Prada which is 15x more expensive that silver)

Question 38

What is the gene for Russel Silver and BWS?

Answer 38

11p15 Codes for IGF2 and is a paternally expressed growth factor.

Question 39

What is imprinted in BWS?

Answer 39

MATERNAL imprinting. If you dont have mum's genes, tend to be BIG like a MAN (remember BWS and Russel Silver linked) (Remember Angelman and Prada linked, Angel wears Prada which is 15x more expensive that silver)

Question 40

What is imprinted in Russel Silver?

Answer 40

PATERNAL imprinting Dont have dad's genes so small and petite

Question 41

What is imprinted in Russel Silver?

Answer 41

PATERNAL imprinting Dont have dad's genes so small and petite(remember BWS and Russel Silver linked)

Question 42

What is the familial risk for ASD for sibling?

Answer 42

Twins: 60% Siblings: more recently >10% recurrence 2 siblings with ASD >20%

Question 43

What is the difference between Cohen syndrome and Prada-Willi? Hint- Who can't see?

Answer 43

Both have hypotonia and truncal/central obesity in later periods. Cohen: Also has vision problems, beak nose, retinopathy, neutropenia. 'COHEN CANNOT SEE' Prader Willi: Has almond shaped eyes, severe hypotonia and feeding difficulty in early neonatal period, OCD and genital hypoplasia.