Cytogenetics Flashcards
What is the definition of mosaicism?
variation of at least 2 cell lines
Is Mosaicism acquired or inherited?
Acquired, it can not be inherited
What aneuploidy is not viable?
Many Monosomies with an exception of 45X is viable.
What is 47XXY?
Klinefelter syndrome
what is genetic disease is caused by trisomy 21?
Down syndrome
what are clinical features of down syndrome
Multiple System Defects in in the heart, brain and lung,
Usually Infertile
Developmental delay
(M.U.D)
What genetic disease is caused by Trisomy 13?
Patau Syndrome
What are clinical features of Patau syndrome?
Cleft lip and paltate
“Punched out scalp”
Polydactyly
Rocket-bottom feet
(C.P.P.R)
What genetic disease is caused by Trisomy 18?
Edwards Syndrome
What are the the clinical features of Edwards syndrome?
Hypoplasia of muscles
Polydactly
Cross Fingers
Rocket-bottom feet
( H. PCR)
What does it mean by “females are mosaics for heterozygous traits”?
Means that some portion of their cells express one trait and some cells have a different traits.
(Basically due to x-inactivation, women can have heterozygous traits produced from their maternal X and paternal X.)
what is a disomy?
is presence of 2 chromosomes
what is isodisomy?
is 2 chromosomes from the same source
ie. duplication of 1 chromsome
what is Heterodisomy?
is 2 different chromosomes
what is a diploid?
presence of 2 copies of each unique chromosome
what is a haploid?
one copy of each unique chromosome
What is XXX female features?
- 1 /1000 female births
- Tall stature
- due to meiosis I maternal error
- usually Phenotypically normal
- normal fertility
- normal intelligence
What is features of an XYY male?
1/1000 births
- Tall stature
- due to paternal meiosis I error
- phenotypically normal
- normal fertility
- normal intelligence
What is the genetic disease for karyotype 47, XXY?
Klinefelter Syndrome
clinical features of Klinefelters Syndrome?
- 1/1000 births
- Tall stature
50% due to meiosis I error in dad
- Infertility
- female characteristics may develop
- learning deficit possible
(L.I.F.T 50)
What genetic disease is associated with karyotype 45X?
Turner Syndrome
What are some clinical features of Turner Syndrome?
1/5000 live female births
- Short Stature
- Webbed neck in utero
- usually Infertile
- 10% are mosaics (with 45X/XX and 45XY
If you end up with the 45X/XY what can happen for male and female phenotype?
- If you show male phenotype, you are normal
- If you show female phenotype, then you need to surgically remove your gonads or be at risk of gonadoblastoma
What is the clinical features of XY female?
1/20000 live births
-Phenotypically normal female with testes
Infertility
Androgen Insensitivity
(P.I.A.)
What are the clinical features of XX male?
1/20000 live births
X-Y recombination near pseudoautosomal region
Usually nomal, possible Klinefelter phenotype
Reciprocal translocation (TDF/SRY is replaces by Xp material which is transmitted to child, resulting in Turner female phenotype
what is a balanced structural abnomality?
when all material is present but is just re-arranged
What is unbalanced structural abnormalities?
this is when material is missing or duplicated
What is a contiguous genome?
associated genomes on the same locus but are unrelated to eachother
ie. VCFS and William Beuren Syndome
What are the clinical features of VCFS?
Short Stature
Facial Anomalies,
Cardiac anomalies
Cleft palate and lip
Learning disability
Weak immune system
Hypotonia
What are the clinical features of William Beuren Syndrome?
Outgoing and friendly
Usually low IQ
Thickening of skin
Renal Anomalies
Excellent music skills, suck at math
Stellate Iris
Skeleltal muscle and joint limitations
Blue sclera
Supravalvular aortic Stenosis
(O.U.T. R.E.S.t B.S)
What is alternate segregation?
- Chromosome 1 segregrate together and chromosome 2 segregate together forming balanced gametes
- No rearrangement and balanced translocation
What is adjacent 1 segregation?
When chromosome one segregate and the 2s segregate together (centromeres move to opposite poles), leading to unbalanced translocation.
-will have duplications and deletions of gene regions.
what is adjacent 2 segregation?
Same as adjacent 1 but instead centromeres move to the same pole (normally they are suppose to move to opposite poles)
What is 3:1 segregation?
This is a segregation in which you end up with 3 chromosome in one cell and 1 chromosome in another.
-Products are highly unbalanced and unlikely to be viable
Balanced translocations important features are?
- they can be de novo
- Translocations can be inherited
- Carriers are usually phenotypically normal
- though chromosomal material is there, there is rearrangement
What is the significance of a balanced translocation for an individual?
- poses an increased risk of another pregnancy having a unbalanced chromosome complement
- increased risk of abnormal live born
FISH (fluorescence In-Situ Hydbridization) How does it work?
Using a fluorescent colored probe allows binding to the denatured DNA before it re-aneals
Benefits of FISH
- allows you to detect chromosomal re-arrangements, duplications, and deletions
- easy to score using colors
- Does not require metaphase cells
- accurate
Disadvantages of FISH
- your probe is locus and chromosome specific ( this means you have to already need to have an idea of what you are looking for)
- probes do not cover the entire abnormality
- a very small deletion or duplication may be to small for probe to hybridize
- variant duplication or deletion may not even be detected if it is outside of the boundary of the abnormality
When do I use FISH?
when you can’t screen all your chromosomes
If you think you know the disease
To maximize your results
If the karyotype analysis has given you chromosomes (use that info)
What is Identity by Descent?
aka consanguity
- have an increased risk of autosomal recessive traits
- have increased risk of expression of autosomal recessive traits
What is Microarray benefits?
- useful for identifying CNV 10kb or larger
- identifies unbalanced translocations
- detects AOH (absence of heterozygosity, ROH (region of homozygosity), IBD (identity by descent)
- detects mosacism
Disadvantages to microarrays
- can not detect balanced translocations
- or CNV’s less than 10kb
What is NGS sequencing
-technology which performs a genome-wide scan to detect for mutations associated with patients medical concerns
Strengths of NGS sequencing
- Targeted of Genome wide screen
- detection of very small abnormalities (<21bp)
Weaknesses of NGS sequencing
- Time for reporting
- cost
- you get alot of data that has no clinical correlation
- difficulty detecting mosacism, translocations, and IBD
If I wanted to detect balanced translocations what cytogenetic tools would I use?
FISH, NGS sequencing (more expensive)
What tests would I use if I wanted to detect unbalanced translocations?
Microarray, karotype analysis,
If I wanted to do some genomic screening what tests would I use?
Microarray and NGS sequencing
What molecular tool would I use if I was involved in a case of Uniparental disomy?
Microarray or molecular analysis
what is X-inactivation?
- done in females to provide gene dosage compensation
- heavy methylation of one of female X chromosomes occurs turning it off.
- this is what allows for mosaics with heterozygous traits. (some sex cells with one trait and some other cells with another trait)
Genomic Imprinting
chromosome methylation patterns specific to parents, that are passed from each of them to the zygote.
what does Male vs. Female effect in Imprinting mean?
The male imprinted chromosome (chromosome with methylation patterns) when affected with disease causing mutations or translocations, it can give different epigenetic disease to child than female’s imprinted chromosome affected by mutation and deletion.
ie. Prader Wili vs. Angelman Syndrome (caused by same mutation, but different genomic imprint)
what is Uniparental disomy
inheritance of a pair of chromosomes from 1 parent (in contrast to the normal being one from mom and one from dad)
-usually can not be detected using karyotype, must use molecular analysis tech.
what is uniparental isodisomy?
duplication of the same chromosome from one parent
what is uniparental heterodisomy
different 2 chromosomes from the same parent.
What is biparental heterodisomy?
two different chromosomes from different parent.
How can you get Prader Wili Syndrome?
1) deletion in the paternal impint being passed on with maternal imprint
2) dad’s meiosis error (not re-imprinting his paternal chromosome causing his maternal imprint to be passed on along with mom’s paternal imprint (2 maternal imprints)- results in only functional maternal alleles
Clinical features of Prader Wili Syndrome
small, hypotonia, and gain weight easily,
-dont have satiety pathways so never get full
clinical features of Angelman Syndrome
- severly mentally retarded
- friendly but can’t hold on normal conversations
- their discourse (spoken communication) often punctuated with inappropriate laughter.
