Cytogenetics & Copy Number Variation Flashcards
Microdeletion/microduplication syndromes are those that involve deletion or duplication of ____ of DNA, and cannot be visualized by ____
<10 Mb
G-banding
Deletion 22q11.2:
DiGeorge/Velcro-cardio-facial syndrome
Deletion 15q11.2:
Prader Willi Syndrome/ angelman syndrome
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 ____ ___ ____
Low copy repeats (LCR)
The deletions is generated by_____ _____ ____ between these low copy repeats (LCR)
Non-Allelic homogolous recombination
Such low copy repeats also flank the breakpoints of other ____ _____ ____ (Williams, 22q11.2)
Recurrent microdeletion syndromes
Low copy repeats result from ____ _____ of the genome. Low copy repeats are Typically 10-500 kb in size. They Typically share ______ identity
Segmental duplication
95 to 99% identity
The genomic architecture of certain chromosomal regions (with intervening ___ ___ ___) predispose them to NAHR and the generation of duplications and deletions
Low Copy Repeats (LCR)
Diagram of nonallelic homologous recombination
22q11.2 deletion syndrome has high ____ ____. Most common symptoms include _____ ____, ____ ____, and ____
Variable expressivity
Cardiac anomalies
Immune deficiency
Hypocalcemia
_____ 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 ____
Hybridization
Array
Laser scanner
Duplication
Deletion
-1 equals _____ of one copy
0 equals ____ ___ or gain
Loss
No loss
Two different clinical disorders are caused by the same ___ ___ ____ on chromosome 15: ___ ___ syndrome and ____ syndrome
5 Mb microdeletion
Prader Willi
Angelman
Clinical findings in Prader Willi syndrome:
Infant:
Childhood/adulthood:
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
Clinical symptoms of Angelman syndrome:
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
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 ____
5 Mb deletion
Imprinting
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
Expression
Paternally
Maternally
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
Methylation
Microarray
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
Paternally
Maternally
UBE3A
This pregnancy underwent uni-parental disomy
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
Neutrophil
Phagocyte
Immune
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
Basophil
Histamines
Allergies
Blood vessels
An ______ releases ____ that kill bacteria and parasites, but also causes tissue damage. They circulate in the ____ and migrate to tissue
Eosinophil
Toxins
Blood
Neutrophils, basophils, and eosinophils are all _____.
Granulocytes
Monocyte, neutrophil, mast, cell, macrophage, dendritic cell are all _____
Phagocytes
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
Mast cell
Histamines
Heparin
Allergic
Connective
Mucus
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
Macrophage
Blood
____ ____ cells kill ____ cells and virus infected cells. They circulate in the ____ and migrate into tissue
Natural killer
Tumor
Blood
______ 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.
Dendritic
Adaptive
Epithelial
Lymph nodes
____ ____ 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.
Innate lymphoid cells (ICLs)
T-helper
Intracellular
Epithelial
Need to use ____ or ___ to detect microdeletions
FISH
microarray
Uneven crossing over is ____ ____ ____. This occurs because the low copy repeat regions are almost identical, they match up during recombination by accident
Non-Allelic homologous recombination
Array SGH shows green for a ____ and red for a ____
Duplication
Deletion
In Prader Willi syndrome, one defining symptom is progressive _____, meaning an increased appetite
Hyperphagia
If the paternally derived allele is expressed exclusively, then the ____ inherited allele is being silenced through imprinting. And vice versa
Maternally
Inheritance of AS:
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?
Could be either one
We need to know if they inherited the mutation from mom or dad
If someone has a UB3E mutation, is it possible for them to have no clinical findings?
Yes, because if they inherited this mutation from their father , it will be silenced through imprinting
True or false:
If mom has the UBE3A variant, she will pass AS to all of her children
True
____ ____ 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
Uniparental disomy
Trisomy
Trisomic rescue
Review diagram of trisomy rescue
