RL Lectures 41 and 42: Chromosomes and Cytogenetics Flashcards by Shay Guetz

What causes the majority of spontaneous abortions in the first trimester?

chromosomal abnormalities

66%

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What is the overall incidence of chromosomal abnormalities in the live born population?

~1 in 125

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When are chromosomes visible?

mitotic phase of the cell cycle

karyotype requires cells that are spontaneously dividing or in cells where division has been induced

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How is karyotyping performed?

blood sample is taken and G-banding procedure allows for discrimination of banding per chromosome which can identify all 23 pairs of chromosomes

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List the sections of the chromosomes.

p-arm (short arm)
q-arm (long arm)
centromere (central condensed region essential for mitotic spindle attachment)
telomere (cap at the end)

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What are metacentric chromosomes?

chromosomes whose arms have very similar lengths

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What are sub-metacentric chromosomes?

chromosomes where the p-arm is visually shorter than the q-arm

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What are acrocentric chromosomes?

chromosomes where the p-arm is very short and only contains repetitive information and ribosomal RNA genes

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List the acrocentric chromosomes.

13, 14, 15, 21, and 22

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List the kinds of aneuploidy.

monosomy/ deletion (missing chromosome or missing part of a chromosome)
disomy/ duplication (additional chromosome or part of a chromosome)

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How do aneuploidys occur?

failure of the chromosomes to properly segregate during division (most commonly meiotic 1 non-dysjunction)

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What is Down Syndrome?

Trisomy 21
most common trisomy seen in live births
1 in 800
95% due to meitotic 1 non-dysjunction
highly correlated with AMA
life expectancy ~60 years

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What are the symptoms associated with Down Syndrome?

ID
short stature
hearing loss
seizures
heart malformations
digestive tract malformations
increased disease risk
distinct facial features

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What is Edward Syndrome?

Trisomy 18
1:6,000 live births
95% result in spontaneous abortion or miscarraige
poor survival rates (4 days average)

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List the symptoms of Edward Syndrome.

rocker bottom feet
overlapping fingers
multiple congenital organ anomalies
restricted growth
microcephaly
short palpebral fissures
small chin and mouth
low-set ears
cutis aplasia

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What is Patau Syndrome?

Trisomy 13
1 in 10,000 live births
life expectancy about 130 days

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What features are present in babies with Patau Syndrome?

distinctive midline defects (cleft lip/palate)
multiple congenital organ anomalies
hypertelorism
holoprosencephaly
polydactyly

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Describe trisomy mosaicism.

typically have attenuated features of the trisomy

result from non-dysjunction of the chromosomes after fertilization

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What is Turner Syndrome?

Monosomy X
1 in 5,000 live female births
99% of embryos spontaneously aborted
loss of PAR region

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What are the symptoms associated with Turner Syndrome?

webbed neck
lymphedema
short stature
coarctation of aorta
structural kidney defects
ovarian dysgenesis

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What is PAR?

pseudoautosomal regions

repeat sequences at both ends of sex chromosomes that act as autosomal genes and escape X-inactivation

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What is Kleinfelter syndrome?

47,XXY
1 in 1000 live male births
half maternal and half paternal in origin
one X chromosome is inactivated but three pairs of PAR regions are still expressed

What symptoms are associated with Kleinfelter Syndrome?

small testes
low testosterone
geynecomastia
no spermatogenesis
taller and thinner
learning issues
ADHD

What is Super Female Syndrome?

47, XXX
1 in 1000 female births
mostly maternal in origin
only one X is active but still have three pairs of PAR genes active

List the symptoms of Super Female Syndrome?

tall stature balance problems generally fertile risk of speech delay and learning issues

What is Jacob syndrome?

47, XYY 1 in 1000 live male births paternal in origin only one X is active but three pairs of PAR regions are present

What are the symptoms of Jacob Syndrome?

tall but normally proportioned | mostly completely asymptomatic

What screenings can be used to detect risk of an aneuploidy in the first trimester?

NT PAPP-A f-bhCG

What percent of pregnancies are lost due to aneuploidy per trimester?

1st: 66% 2nd: 20%

What results on a first trimester screening would indicate increased risk for Down Syndrome?

increased NT low PAPP-A high f-bhCG

What results on first trimester screening would indicate increased risk for Edward Syndrome?

increased NT low PAPP-A low f-bhCG

What results on first trimester screening would indicate increased risk for Patau Syndrome?

increased NT low PAPP-A low f-bhCG

What serum analyte screenings can be used to detect risk of aneuploidy in the second trimester?

estriol inhibin A hCG AFP

What results on a quad screening would indicate increased risk for Down Syndrome?

low AFP low estriol high hCG high Inhibin A

What results on a quad screening would indicate increased risk for Turner Syndrome?

decreased AFP decreased estriol very high hCG very high inhibin A

What results on a quad screening would indicate increased risk for Edward Syndrome?

low estriol very low hCG low AFP

What results on a quad screening would indicate an increased risk for Patau Syndrome?

increased AFP

How would you confirm the results of a triple or quad screening?

CVS | amnio

What is uniparental diploidy?

normal number of chromosomes, but they are all from one parent pathogenic (most clinically significant with chromosomes containing imprinted regions)

What chromosomes contain imprinted regions?

6, 7, 11, 14, 15, 16

What is the result of paternal origin uniparental diploidy?

complete hydatidiform mole (no fetal tissue, only trophoblast hyperplasia, leading to carcinoma) results from an egg that lacks a nucleus and is fertilized by one normal sperm

What is the result of maternal origin uniparental diploidy?

``` ovarian teratoma (disorganized empbryonic material) results from an activated unovulated oocyte ```

What is triploidy?

having three sets of chromosomes (total of 69) | caused by polyspermy (fertilization of a normal egg with two sperm resulting in a partial mole containing fetal tissue)

What is tetraploidy?

having four sets of chromosomes (total 92) | caused by failure of the first zygotic division (usually does not contain fetal tissue and is spontaneously aborted)

Provide examples of deletion syndromes that can be visualized on karyotyping.

Wolf-Hirshhorn syndrome (4p16 terminal deletion)

What are translocations and inversions?

abnormalities in which genetic material is not gained or lost, but rather relocated

What is a balanced translocation?

a translocation where no genes are disrupted occurs when there is a reciporcal interchange of genetic material between two non-homologous chromosomes carriers typically have no phenotype but risk recurrent miscarraige or phenotypically abnormal offspring because gametes may be unbalanced

What is a Robertsonian translocation?

exchange of a full q arm from one acrocentric (homologous or non-homologous) chromosome with the p-arm of another acrocentric chromosome resulting in the loss of the p-arm all genetic material is still accounted for because p-arm is repetitive

What is a pericentric inversion?

two breaks in one chromosome where the area inbetween the breaks inverts and rejoins including the centromere

What is paracentric inversion?

two breaks in one chromosome where the area inbetween the breaks inverts and rejoins confined to only one arm (does not include centromeric region)

What happens when homologous recombination occurs with an inversion?

an elaborate looped pairing is needed during meiosis

What does the loop pairing during meiosis cause?

unbalanced chromosomal abnormality in the conceptus with a partial duplication of one end of the inverted region in conjugation with a partial deletion of the other end of the inverted region

Describe the formation and results of ring chromosomes.

tip of p arm is fused with the q arm on the same chromosome genetic material at the tip can be lost, creating a terminal deletion easily loose the whole chromosome during mitosis