Chromosomes And Cytogenetics Flashcards
What are chromosomes?
Complex structures of DNA, his tone proteins and non-his tone proteins
What is a common cause of infertility no recurrent miscarriage?
Chromosome abnormalities
- 50% of 1st trimester
- multiple congenital anomalies in ~0.5% of newborns
What is polyploidy?
Changes in the number of all chromosomes equally
E.g. Triploidy, tetraploidy
What is Aneuploidy? (~1 in 300 new burns)
Changes in number of one or multiple chromosomes unequally
E.g. Monosomy, trisomy, retraso y
What numerical abnormalities are compatible with life?
13, 18 and 21 (trisomy)
How can triploidy occur?
66% 2 xsperm and 1 egg
10% 1 sperm and a 2n egg
24% a 2n sperm and an egg
How does tetraploidy occur?
Endomitosis
What 3 types of structural abnormalities occur in chromosomal structures?
- Balanced
- Unbalanced
- Aneuploidy (numerical abnormality)
What are the kinds of balanced structural chromosomal abnormalities?
- Translocation
- Inversion
-This is relocation of genetic material
What are the kinds of unbalanced chromosomal structural abnormalities?
- Duplication
2. Deletion
What are the kinds of Aneuploidy chromosomal abnormalities?
- Gain of genetic material
2. Loss of genetic material.
What is the common name of 22q11 deletion?
DiGeorge Syndrome
What test is ordered for karyotyping?
FISH
What are some signs and symptoms of Down syndrome?
Floppy baby (hypotonia)
Excess nuchal skin
Bilateral single palmar crease (simian)
What is the karyotype for Down syndrome?
47,XX+21
47,XY+21
What are some causes of Down syndrome?
95% complete trisomy 21 (Meosis)
4% are robertsonian translocation
1% are mitotic nondisjunction (milder features)
What are some clinical features of Down syndrome?
Nuchal skin Brachycephaly Flat occiput Epicanthic folds Smaller ears with over-folded helix Palpebral folds Atresia Heart problems Strabismus-alignment of eyes Hirschsprung disease (Just recognize them don't memorize all)q
What is Hirschspring disease?
Blockage of the Large intestine
What is the is of a Down syndrome patient?
25-50
What are Down syndrome patients at a higher risk of developing?
- leukemia (ALL or AML) 10-20 times increased risk
- Alzheimer disease at age 40
40% congenital heart disease
-septal defect
What is nondisjunction?
Failure of chromosomes or chromatids to segregate in M1 or M2
If nondisjunction occurred in Meosis 2 what is seen?
Chromosomes are identical
If the nondisjunction occurred in Meiosis 1 what is seen?
The two chromosomes from this parent are not identical
What is recombination (cross over)?
Mixing up of DNA during meiosis
Where does nondisjunction most commonly occur?
Maternally in M1
Which nondisjunction is always from the father?
47,XYY
Always in meiosis 2
How does the risk of Down syndrome increase?
With maternal age
35 is the age where testing is recommended
What is trisomy 13?
Palau syndrome
What are the clinical presentations of trisomy 13?
Cleft lip/palate (often severe) Microcephaly & mental retardation Cardiac defects Genito-urinary and renal defects Polydactyly
How long do babies with trisomy 13 survive?
7 days
What is the common name for trisomy 18?
Edwards syndrome
What are the clinical presentation of trisomy 18 (Edwards syndrome)
Microcephaly CNS and cardiac malformation Prominent occiput Micrognathia Low set ears Short neck Overlapping fingers Renal malformation Limited hip abduction Rocker-bottom feet
What is the mean survival for Edwards syndrome?
14.5 days
What is the karyotype for Turner syndrome?
45,x
What are the clinical presentation of Turner syndrome?
Short stature Delayed pubertal development Amenorrhea Iq ~90 Webbing of neck Broad chest and infertility Infertility
What treatment is used for Turner syndrome?
Estrogen supplementation
Most cases of Turner syndrome are what?
45x/46xx mosaics
What are the clinical presentation of Klinefelter syndrome (47XXY)?
Secondary sex characteristics display feminization (gynecomastia, female distribution of pubic hair) Hypogonadism Infertile due to azospermia Disproportionately long limbs Tall, thin stature In ~85-90
What is the treatment for klinefelters syndrome (47XXY)
Testosterone supplementation
What is triple x syndrome?
47,xxx
Female with tall stature and mild mental deficit
What can you see in fluorescentes stained cells of individuals with additional X chromosomes?
Barr bodies
Normally only 1 Barr body because 1 X chromosome is inactive. Additional X chromosomes also becomes Barr bodies
How do structural chromosomal abnormalities occur?
Chromosome breakage with subsequent reunion in a different configuration
What s a quadrivalent?
When two derived pairs of chromosomes come together during meiosis. When they are pulled in anaphase 6 outcomes are possible (2 balance and 4 unbalanced)
What is a roberstsonian translocation?
Translocation between 2 acrocentric chromosomes (13,14,15,21,22)
P arms are lost (no essential genetic data)
Q arms nod centromeres are retained as fused chromosomes
What is lost in a robertsonian translocation and why is it significant?
P arms are lost
No genetic information is carried on the p arm. It s only repetitive rDNA
When can Robert translocations occur?
When the chromosome is acrocentric
E.g. (21,22,13,14,15)
Are carriers of Robert translocations affected? What about their offspring?
Carriers are asymptomatic but often produce unbalanced gametes which can result in monosomic or trisomic zygote. ( most wont survive)
What are the 6 possible offspring of a 45,xx,rob(14q21q)?
2 healthy (1 normal, 1 balance carrier)
3 prenatal lethal (trisomy 14, monosomy 14, monosomy 21)
1 with Down syndrome
-probably of a child being born with Down syndrome is 1/3
What is a translocation Down syndrome?
An extra copy of the q rm of chromosome 21 due to robertsonian translocation
What is the probability that a balanced 14q21 carrier will have a child with Down syndrome?
1/3 of live born hypothetically
10% for mother and 3% for father empirically
What is the probability that a 21q21q translocation would result in Down syndrome in off spring?
100% of live born off spring would have Down syndrome
What are the possible gametes for offspring from an individual with 21q21q?
Nullisomic for 21: lethal in utero
Disomic for 21: result in trisomic conceptos (Down syndrome child)
What are the chromosomal abnormalities if 2 breaks occur in the same arm of the chromosome?
Paracentric ( flips around and goes back in)
Interstitial deletion ( it goes bye bye)
What happens when there are 2 breaks in different arms?
Pericentric inversion ( it flips round )
Ring chromosome ( they reconnected to the other side and lose genetic information at the ends)
Which type of inversion involve the centromere?
Pericentric inversions
What is the critical region in the 4p arm?
4p16
When does wolf-hirschhorn syndrome occur?
When you have a deletion on the 4p arm
It will be abbreviated as 4p-
What are the clinical presentations of wolf-hirschhorn syndrome?
Face: broad, flat nasal bridge, high forehead (“Greek warrior helmet”)
Microcephaly
Growth retardation
Severe mental deficiency
Hypotonia, seizures
When does cri du chat syndrome occur?
When there is a deletion in the 5p arm
It is abbreviated as 5p-
What are the clinical presentation of cri du chat syndrome?
Cat like cry
Mental deficiency
Microcephaly
Face: hypertelorism, epicanthal folds, downward sloping palpebral fissures
