Cytogenetic Imbalances (2)

Question 1

Name 4 macro deletion syndromes

Answer 1

1) cri-du-chat
2) wolf hirschorn syndrome
3) miller-dieker syndrome
4) smith magenis syndrome

Question 2

Cause of Cri-du-chat, what is the critical region?

Answer 2

Del 5p

Critical region = 5p15.3-5p15.2

Question 3

Features of cri- du-chat?

Answer 3

Cat like cry.
Microcephaly
Poor muscle tone
MR

Question 4

Cause of wolf hirschorn syndrome?

Answer 4

Del 4p

Question 5

Features of wolf-hirschorn syndrome

Answer 5

Prominent forehead
Wide set eyes
Broad beaked nose

GREEK WARRIOR HELMET

Question 6

Cause of miller dieker syndrome?

Answer 6

Del(17)(p13.3) terminal deletion of 17p

Deletion of LIS1

Question 7

Features of miller dieker syndrome?

Answer 7

Lissencephaly

Seizures

Question 8

Cause of smith Magenis syndrome?

Answer 8

Del(17)(p11.2p11.2)

Interstitial deletion of proximal 17p (4mb common deletion region)

Question 9

Features of smith magenis syndrome?

Answer 9

Behavioural problems - self harming and sleep problems

Square face, deep set eyes, full cheeks UNIBROW (synophrys)

Question 10

What is NAHR?

Answer 10

Non-allelic homologous recombination between regions of homologous interspersed throughout the genome

Highly polymorphic regions of low copy repeats

Two LCRs close to each other can result in deletion or duplication of the intervening sequence

Question 11

Name two microdeletion syndromes and a common cause for microdeletion syndromes

Answer 11

DiGeorge syndrome

Williams beuren syndrome

Question 12

Cause of digeorge syndrome?

Answer 12

Dell 22(q11.2q11.2)

Question 13

Features of digeorge

Answer 13

Aortic arch defects
Learning difficulties
Hypercalcaemia

*can be inherited from phenotypically normal parent

Question 14

Cause of Williams-beuren syndrome

Answer 14

Del(7)(q11.23q11.23)

Question 15

Features of Williams beuren syndrome

Answer 15

Heart defects
Elfin-like features
Cocktail party manner
LD (can be talented musicians)
Hypercalcaemia (opposite to degeorge)

Question 16

What are the possible results of segregation of a balanced reciprocal translocation?

Answer 16

1) alternate segregation- normal/balanced products
2) adjacent segregation = unbalanced products as a result of 2:2
3) tertiary or interchange = unbalanced products as a result of 3:1

Question 17

What is tertiary trisomy? Great be an example

Answer 17

3rd chromosome made up of two chromosomes

Emanuel syndrome: 47,XX, +der(22)t(11;22)

Question 18

What common translocation causes Emanuel syndrome?

Answer 18

T(11;22)(q23;q11)

Unbalanced child has gain of 22pter-22q11 and 11q23-11qter in der(22)t(11;22)

Question 19

What is the recurrence rate of Emanuel syndrome to a balanced female carrier? What are risks to female carriers?

Answer 19

Recurrance 5-6%

Increased risk of pregnancy loss

Question 20

Features of Emmanuel syndrome?

Answer 20

MR
Craniofacial abnormalities
Deep set eyes 
Lower set ears
Longer upper lip
Congenital heart defects

Question 21

What can cause a viable adjacent 1 segregation?

Answer 21

T(4;8) (p16;23) recurrent reciprocal segregation
46,xx, der(4) t(4;8) gives a wolf hirschorn phenotype (missing 4p and gained 8p)

46,xx,der(8)t(4;8)- less specific features

Question 22

Name of an inversion including the centromere?

Answer 22

Pericentric

Question 23

Inversion excluding the centromere?

Answer 23

Paracentric

Question 24

What types of inversions have a higher risk f having abnormal children?

Answer 24

Big inversions
Pericentric
End sections are very small

Question 25

What pericentric inversions have the highest risk of having child with LD?

Answer 25

Ones where non inverted segments are small or non-coding (i.e. Acrocentric short arms)

Question 26

What are possible results of meiotic loop at meiosis with a pericentric inversion?

Answer 26

1) normal chromsome
2) inverted chromosome
3) recombinant chromosome dup p distal
4) recombinant chromosome dup q distal

Question 27

What are results of meiotic loop for paracentric inversions?

Answer 27

Normal
Inverted
Dicentric recombinant chromosome- most likely lost
Acentric recombinant chromosome- mostly lost

Question 28

What is it called when one chromosome is inserted into another?

Answer 28

Interchromosomal insertion (3 break points)

Question 29

What is it called when a segment of one chromosome is inserted into dif place of same chromosome ?

Answer 29

Intrachromosomal insertion

Question 30

How is a ring chromosome formed?

Answer 30

Formed from a single chromosome with loss of material and fusion of the p and q arms

Question 31

True or false: less material is lost with large ring chromosomes

Answer 31

True- usually in place of normal chromosome

Question 32

What is dynamic mosaicism?

Answer 32

Frequent errors at mitotic division eg. Rings

• loss of the ring
• additional copies
• double size

Question 33

Features of generalised ring chromosome syndrome (large ring replacing chromosome)

Answer 33

Growth restriction/ short stature

Question 34

What does c-banding do?

Answer 34

Stains constitutive heterochromatin (non coding genetic material) dark - use to establish significance of marker

Question 35

What does silver staining do?

Answer 35

Uses silver nitrate- results in a dark deposit corresponding to satellite stalks of Acrocentric chromosomes- if marker pos then made from Acrocentric chromosome and is non coding

Question 36

Resolution of karyotyping and fish?

Answer 36

G banding 3-5 me

Fish 100s kb

Question 37

Cons of arrays

Answer 37

Only detects genetic imbalance
Not imprinting
No positional information
Mosaics may not be detected

Question 38

Pros of array

Answer 38

High resolution
Genome wide
Does not require viable tissue or cell culture