Cytogenetics & Copy Number Variation

Question 1

Microdeletion/microduplication syndromes are those that involve deletion or duplication of ____ of DNA, and cannot be visualized by ____

Answer 1

<10 Mb
G-banding

Question 2

Deletion 22q11.2:

Answer 2

DiGeorge/Velcro-cardio-facial syndrome

Question 3

Deletion 15q11.2:

Answer 3

Prader Willi Syndrome/ angelman syndrome

Question 4

Most deletions in AS and PWS and those of 22q11.2 are exactly the same size due to the fact that genomic regions that immediately flank the deleted regions are composed of ____ ___ ____

Answer 4

Low copy repeats (LCR)

Question 5

The deletions is generated by_____ _____ ____ between these low copy repeats (LCR)

Answer 5

Non-Allelic homogolous recombination

Question 6

Such low copy repeats also flank the breakpoints of other ____ _____ ____ (Williams, 22q11.2)

Answer 6

Recurrent microdeletion syndromes

Question 7

Low copy repeats result from ____ _____ of the genome. Low copy repeats are Typically 10-500 kb in size. They Typically share ______ identity

Answer 7

Segmental duplication
95 to 99% identity

Question 8

The genomic architecture of certain chromosomal regions (with intervening ___ ___ ___) predispose them to NAHR and the generation of duplications and deletions

Answer 8

Low Copy Repeats (LCR)

Question 9

Diagram of nonallelic homologous recombination

Answer 9

Question 10

22q11.2 deletion syndrome has high ____ ____. Most common symptoms include _____ ____, ____ ____, and ____

Answer 10

Variable expressivity
Cardiac anomalies
Immune deficiency
Hypocalcemia

Question 11

_____ to ____ of DNA fragment is a way to visualize deletions and duplications. You take a patient and control DNA, mix them together, place into a ___ ___. Green shows a ____, red shows a ____

Answer 11

Hybridization
Array
Laser scanner
Duplication
Deletion

Question 12

-1 equals _____ of one copy
0 equals ____ ___ or gain

Answer 12

Loss
No loss

Question 13

Two different clinical disorders are caused by the same ___ ___ ____ on chromosome 15: ___ ___ syndrome and ____ syndrome

Answer 13

5 Mb microdeletion
Prader Willi
Angelman

Question 14

Clinical findings in Prader Willi syndrome:
Infant:
Childhood/adulthood:

Answer 14

Hypotonia; failure to thrive, Feeding/sucking difficulties, Characteristic facial features, developmental delays

Progressive hyperphagia (increased appetite) and fat deposition, sleep apnea, behavioral issues, anxiety, compulsive skin picking, high pain tolerance, and cognitive disability

Question 15

Clinical symptoms of Angelman syndrome:

Answer 15

Microcephaly, protruding jaw, developmental delays, ataxia gait, severe language delay, seizures, happy demeanor, inappropriate bursts of laughter, high pain tolerance, difficult sleeping, hyperactivity, and scoliosis

Question 16

In 70% of individuals with PWS or AS, there is a __ ___ ___ in 15q.11.2. The deletions are identical but the clinical syndrome are different due to ____

Answer 16

5 Mb deletion
Imprinting

Question 17

Imprinting is differential ___ of a gene depending upon the parent of origin. PWS genes are expressed exclusively from the _____ derived chromosome 15. AS genes are expressed exclusively on the ___ derived chromosome 15

Answer 17

Expression
Paternally
Maternally

Question 18

Two tests for PWS and AS:
1. ____ testing: can tell if the genes are expressed or not
2. _____: can tell you if the genes are present or deleted

Answer 18

Methylation
Microarray

Question 19

Blue: ____ expressed genes, lack of expression leads to Prader Willi
Red: _____ expressed genes, lack of expression leads to angelman syndrome. _____ is the single gene responsible for AS. There is no single gene responsible for PWS

Answer 19

Paternally
Maternally
UBE3A

Question 20

Answer 20

This pregnancy underwent uni-parental disomy

Question 21

A _____ is a first responder to the site of infection. It is a _____ and represents 40 to 60% of all leukocytes. It releases toxins that kill or inhibit bacteria. It recruits other ____ cells

Answer 21

Neutrophil
Phagocyte
Immune

Question 22

A _____ is responsible for defense against parasites. It releases _____ that cause inflammation and may be responsible me for ____ reactions. It circulates in the ____ ___ into tissues

Answer 22

Basophil
Histamines
Allergies
Blood vessels

Question 23

An ______ releases ____ that kill bacteria and parasites, but also causes tissue damage. They circulate in the ____ and migrate to tissue

Answer 23

Eosinophil
Toxins
Blood

Question 24

Neutrophils, basophils, and eosinophils are all _____.

Answer 24

Granulocytes

Question 25

Monocyte, neutrophil, mast, cell, macrophage, dendritic cell are all _____

Answer 25

Phagocytes

Question 26

A ____ ____ dilate blood vessels and induces inflammation through release of _____ and _____. Recruits macrophages and neutrophils involved in wound healing and defense against pathogens but can also be responsible for ___ reactions. They are found in ____ tissue, and ____ membranes

Answer 26

Mast cell
Histamines
Heparin
Allergic
Connective
Mucus

Question 27

A _____ is a phagocytic cell that consumes foreign pathogens and cancer cells. It stimulates response of other immune cells. They are found in the ___ and migrate into a tissue

Answer 27

Macrophage
Blood

Question 28

____ ____ cells kill ____ cells and virus infected cells. They circulate in the ____ and migrate into tissue

Answer 28

Natural killer
Tumor
Blood

Question 29

______ cells present antigens on its surface there by triggering the _____ immune system. They present in ____ tissue, including skin, lung and tissues of the digestive tract they migrate to ___ ___ upon activation.

Answer 29

Dendritic
Adaptive
Epithelial
Lymph nodes

Question 30

____ ____ cells produce cytokines analogous to ___ ___ cells. They participate in defense against _____ microbes, helminths, extracellular, fungi, and bacteria. They present in ____ tissues, particularly the gut, mucosa and long. Very rare in peripheral blood.

Answer 30

Innate lymphoid cells (ICLs)
T-helper
Intracellular
Epithelial

Question 31

Need to use ____ or ___ to detect microdeletions

Answer 31

FISH
microarray

Question 32

Uneven crossing over is ____ ____ ____. This occurs because the low copy repeat regions are almost identical, they match up during recombination by accident

Answer 32

Non-Allelic homologous recombination

Question 33

Array SGH shows green for a ____ and red for a ____

Answer 33

Duplication
Deletion

Question 34

In Prader Willi syndrome, one defining symptom is progressive _____, meaning an increased appetite

Answer 34

Hyperphagia

Question 35

If the paternally derived allele is expressed exclusively, then the ____ inherited allele is being silenced through imprinting. And vice versa

Answer 35

Maternally

Question 36

Inheritance of AS:

Answer 36

Question 37

If someone has the 5 Mb deletion in 15q11.2, do they have AS or PWS?

What more information do we need to determine phenotype?

Answer 37

Could be either one

We need to know if they inherited the mutation from mom or dad

Question 38

If someone has a UB3E mutation, is it possible for them to have no clinical findings?

Answer 38

Yes, because if they inherited this mutation from their father , it will be silenced through imprinting

Question 39

True or false:
If mom has the UBE3A variant, she will pass AS to all of her children

Answer 39

True

Question 40

____ ____ is when the embryo receives two copies of either maternal or paternal chromosomes. This occurs when an embryo has ____ and undergoes ____ ____. This causes 20 to 30% of PWS

Answer 40

Uniparental disomy
Trisomy
Trisomic rescue

Question 41

Answer 41

Review diagram of trisomy rescue