Genetics Week 1 Flashcards
Any chromosome # NOT a multiple of 23.
Aneuploid.
If a cell has one of 2 complete extra sets of chromosomes, it’s called….
Polyploid.
The most common cause of Triploidy is…..
What else can cause it?
Polyspermy - egg gets fertilized by 2 sperm.
Can also happen via failure of cell division.
Will you ever see a polyploid baby in the nursery?
NOPE - all forms of polyploidy (tri/tetraploidy) are fatal. Spontaneous abortion.
T/F: All monosomies are LETHAL.
TRUE
If you have abnormalities of sex chromosomes, what is required for survival?
at least one copy of the X
Name the only AUTOSOMAL aneuploidies associated with live births.
Trisomies 13, 18, 21
ALL MONOSOMIES LETHAL
What syndrome has a 45, X karyotype?
Turner’s Syndrome
What syndrome has a 47, XY +21 karyotype?
TRISOMY 21: A male with Down’s Syndrome.
THE MOST COMMON CHROMOSOMAL DISORDER
How does Trisomy 21 occur?
95% Maternal Meiosis 1 nondisjunction
5% Robertsonian Translocation
What syndrome is associated with a 47,XX,+18 karyotype?
Clinical characteristics?
Edwards Syndrome: Trisomy 18
Rocker bottom feet and clenched hands.
How does Trisomy 18 Occur?
Maternal nondisjunction 100% of the time.
What is the Karyotype of Patau Syndrome?
How does this occur?
47,XY,+13
80% maternal nondisjunction
20% Robertsonian translocation
What defects are associated with Trisomy 13?
Midline defects - omphalocele, cleft lip/palate, holoprosencephaly
Is an embryo with X chromosome nullisomy viable?
Nullisomy means “No Copy” so NO! Must have at least 1 X chromosome to survive.
What is the most common abnormality resulting in spontaneous abortion?
Turner’s Syndrome, 45,X
SOLE MONOSOMY ASSOCIATED WITH LIVE BIRTH!!!
Are any mental defects seen in Turner’s? What is seen?
NORMAL INTELLIGENCE - no secondary sex organs so the girls are not fertile and never get a period.
How does Turner’s Syndrome occur? Aka.. which parent’s fault is it?
50% of the time it’s PATERNAL nondisjuction.
35% it’s Mosaicism, resulting in very mild phenotype
Is nondisjunction more common in sex chromosomes or autosomes?
Sex chromosomes, because they aren’t homologs.
47,XXY is more commonly known as……
What is the etiology of this disease? (Which parent is “at fault”)
Kleinfelter’s Syndrome.
BOTH PARENTS : 50% maternal nondisjuction, 50% paternal nondisjuction.
Does Kleinfelter’s syndrome have associated mental retardation?
NOPE, just a lowered IQ and a micropenis. Possibly man boobs.
What is the etiology of XXX (Triple X) Syndrome?
Maternal nondisjuction… just makes sense
Describe the etiology of 47, XYY Syndrome.
Paternal Meiosis II Nondisjuction. - aggression issues, learning/attention problems.
Way too much of a man.
The number 1 side effect of a chromosomal abnormality is…..
Intellectual disability
Describe Karyotyping as a genetic test. Strength? Weakness? What is it good for?
Karyotyping:
- Diagnostic
- Gold standard for prenatal diagnosis of Aneuploidy
- can’t detect microabnormalities
Describe CVS.
Chorionic Villus Sampling:
- late 1st Trimester
- transabdominal or transcervical aspiration to get chorionic villi from developing placenta
After 10 weeks has past, and the mom decides she doesn’t want an invasive prenatal testing procedure done, what test is left?
NIPS: Non-Invasive Prenatal Testing:
- Samples fetal DNA in maternal blood
- cfDNA = cell-free DNA
- A positive test calls for INVASIVE CONFIRMATION
- Only tests chromosomes 13, 18, 21, and sex
- compounds each sequence obtained from cfDNA to ensure full sequence of kid is there.
Describe an Amniocentesis.
15-17 weeks
Invasive
- Shed fetal epithelial cells in the amniotic fluid are collected and the live ones (very few) are cultured.
- Can run a FISH test on the cells that survive (1-2 days)
- Karyotype soon after to confirm (7-10 days)
What does FISH stand for?
Describe the test.
Fluorescence In-Situ Hybridization
- specific DNA probes hybridize to complementary DNA in the patient’s chromosome
- visualized via fluorescence microscopy
After a FISH test, can you say with certainty that the fetus is chromosomally normal?
NOPE! FISH only detects chromosomal abnormalities on chromosomes 13, 18, 21, and sex chromosomes.
Another chromosome may be messed up.
If a positive NIPS test occurs, what happens next?
Non-invasive prenatal screening requires followup with an invasive procedure like CVS or AMNIOCENTESIS to confirm a positive result.
What is the main drawback of FISH?
Results are limited to the scope of the probes used.
What is the only test that will show all CHROMOSOME NUMBER abnormalities?
Karyotype.
… performed after CVS or Amniocentesis.
Do balanced or robertsonian translocations have phenotypic manifestations?
Not in the carrier. The amount of genetic material remains the same. The problem occurs during meiotic segregation, when they fused/translocated chromosomes are passed on.
There is REPRODUCTIVE RISK involved with any translocation. May be Monosomy or Trisomy.
The long-arm fusion of any 2 acrocentric chromosomes is called a ________________.
Robertsonian Translocation
Name the 5 acrocentric chromosomes. Of these, a Robertsonian Translocation in which 2 are viable?
13, 14, 15, 21, 22
13 and 21 are viable
A carrier of a balanced Robertsonian Translocation has a chromosome # of __________.
45
What unbalanced chromosomal segregation pattern can result in partial monosomy AND partial trisomy?
Isochromosome - where the 2 p arms and 2q arms separate.
What syndrome will a child with 46,XY,i(21q) have?
Translocation Downs Syndrome.
An isocromosome involving the 2 q arms of chromosome 21 is the same as a robertsonian translocation of chromosome 21.
Think about it. Acrocentric p arms.
Paracentric and Pericentric inversions. Are the balanced or unbalanced?
Paracentric inversion - same arm
Pericentric inversion - p and q arms
Both are balanced because the amount of DNA doesn’t change.
Reciprocal translocation carriers produce 3 types of gametes. What are they?
Normal
Balanced carriers
Affected/Unbalanced - monosomy/trisomy
When is genetic testing for parental carriers of translocations indicated?
After concurrent losses of pregnancies.
3-5% of couples with recurrent pregnancy loss have a translocation of some sort.
T/F Robertsonian translocations can occur between ANY acrocentric chromosome.
True. Can be between 21 and 21 or 14 and 21 or any of them!
The only robertsonian translocation (unbalanced) that can survive are those with 13 and 21.
Which has the higher recurrence risk? Nondisjuction downs or Robertsonian Downs?
Robertsonian! –> All it takes is an abnormal gamete from the mom usually
Balanced carriers of isochromosomes have what chance of having a healthy offspring?
Close to 0% because all of them are unbalanced.
What 3 tests diagnose partial monosomy and partial trisomy?
Karyotype, FISH, and Array CGH
To test the genome using a normal cytogenetic approach, what phase must the harvested, cultured cells be in?
What about when using molecular approaches?
METAPHASE
When using a molecular approach, cell can be in Interphase, metaphase, or you can even use genomic DNA
Small partial monosomy and small partial trisomy can occur by what happening to a chromosome>
Microdeletions and Microduplications.
What type of testing MUST be used for micro deletions?
Molecular testing - normal cytogenetic testing cannot detect abnormalities this small.
Use FISH or Array CGH
An interstitial microdeletion encompassing 15q12 (resulting in partial monosomy of a critical region) results in what 3 diseases?
Prader-Willi or Angelman Syndrome, based on the parent of origin.
What is a low copy repeat’s role in the generation of micro deletions and micro duplications?
during crossing over, the chromosomes misalign due to a number of LOW COPY REPEAT segments of corresponding DNA. Misalignment results in one chromosome with a duplication and one with a deletion.
FACT: Low copy repeats provide a common mechanism of segmental aneuploidy.
Yep.
What test will tell you if a Downs child has a robertsonian translocation or a nondisjuction?
FISH or Array CGH?
FISH: Can visualize the chromosomes and tag them to see exactly where any repeats lie.
Array CGH can only tell you if there is an excess or not enough DNA. Doesn’t say where it is located.
Can an Array CGH detect a balanced robertsonian translocation carrier?
NO! Array CGH can only detect imbalance of DNA.
An Array CGH of a carrier of a balanced robertsonian translocation will appear NORMAL!.
So what is an Array CGH good for?
Detecting really small imbalances in the genome. It scans the whole genome, unlike the FISH test, which required specific hybridized sequence and can only test certain parts of the DNA.
Karyotypes can’t detect microdeletions or microduplications either. Array CGH can.
DOES NOT REQUIRE LIVING CELLS
Fact: CMA (Chromosomal Microarray) and Array CGH are the same thing.
Another FACT: They can’t detect point mutations or balanced translocations. ONLY detect imbalance.
