Clinical Cytogenetics Flashcards
What is cytogenetics the study of?
Chromosomes and chromosomal abnormalities
What two issues are chromosomal abnormalities the leading cause of?
- Intellectual disability syndromes
- Pregnancy loss
What is another name for the small arm and long arm of a chromosome?
- Small arm: p
- Long arm: q
What is polyploidy? What is triploidy?
Polyploidy: gain of one or more entire chromosome sets
- Triploidy: cells with 3 copies of each chromosome (3N for 69 chromosomes total)
What is aneuploidy? What is the primary cause of aneuploidy?
Aneuploidy: loss or gain of a single chromosome
- Cause: nondisjunction (failure to separate) during either meiosis I or meiosis II resulting in gametes with 1 extra or 1 less chromosome than normal
Define monosomy. What are the outcomes of monosomies in autosomal and sex chromosomes?
Monosomy: only one copy of a specific chromosome (1 is lost)
- Autosomeal monosomies are ALWAYS lethal
- Only X chromosome monosomy is survivable
Define trisomy. What three trisomies are compatible with survival, and why? What is the most common of these three?
Trisomy: three copies of a specific chromosome (1 is gained)
- 13, 18 and 21 are the only survivable trisomies because these three chromosomes have the fewest genes (so while there are more genes than usual, it is not too much for the body to handle)
- Trisomy 21 is the most common
What are two alternative names for Trisomy 21?
Trisomy 21 = Down Syndrome = 47, XY + 21 or 47, XX + 21
What are the 12 characteristics of Down Syndrome?
- Intellectual disability
- Almond-shaped eyes
- Eye abnormalities
- Flat nasal bridge
- Hearing loss
- Protruding tongue
- GI tract obstruction
- Congenital heart defect
- Increased risk for respiratory infection
- Increased risk for leukemia
- Alzheimer’s-like symptoms late in life
- Male sterility
What are the two causes of Down Syndrome, and what is the percentage caused by each?
- Nondisjunction causes 95% of cases
- Robertsonian translocation causes the other 5% of cases
What are two alternative names for Trisomy 18?
Trisomy 18 = Edward Syndrome = 47, XY + 18 or 47, XX + 18
What are the 11 characteristics of Edward Syndrome?
- Small eyes/mouth
- Receding jaw
- Low-set ears
- Intellectual/developmental disability
- Clenched fists/overlapping fingers
- Rocker-bottom feet
- Flexed big toe
- Low weight for gestational age
- Diaphragmatic hernia
- Congenital heart defects
- Kidney defects
What is the cause of Edward Syndrome?
ONLY nondisjunction
What are two alternative names for Trisomy 13?
Trisomy 13 = Patau Syndrome = 47, XY + 13 or 47, XX + 13
What are the 7 characteristics of Patau Syndrome?
- Cleft lip/palate
- Small abnormal eyes
- Large triangular nose
- Extra fingers/toes
- Deafness
- Microcephaly
- Intellectual/developmental disability
What are the two causes of Down Syndrome, and what is the percentage caused by each?
- Nondisjunction causes 95% of cases
- Robertsonian translocation causes the other 5% of cases
Are autosomal chromosome abnormalities or sex chromosome abnormalities tolerated better?
Sex chromosome abnormalities are better tolerated
What does gene expression look like in a normal females versus a female with sex chromosome abnormalities?
Normal females have one copy of most genes of the X chromosome are expressed and two copies of the genes in PARs are expressed
- In a female with sex chromosome abnormalities, there is either increased or decreased gene dosage or PARs
What are two examples of sex chromosome abnormality disorders? Provide an alternative name for each
- Turner Syndrome = 45, X
- Klinefelter Syndrome = 45, XXY
Describe what is happening in terms of gene expression and gene dosage in Turner Syndrome
With Turner Syndrome, only one X chromosome is present so only one copy of PAR genes is expressed
- Decreased gene dosage because only 50% of PAR gene products are available
What are the 10 characteristics of Turner Syndrome?
- Short stature
- Small lower jaw
- Broad/webbed neck
- Low hairline at back of neck
- Visual impairments
- Ear infection/hearing loss
- Learning disabilities (no intellectual disabilities)
- Hypothyroidism
- Congenital heart defects
- Ovarian insufficiency
What are the two treatments for Turner Syndrome? Explain why each is recommended
- Growth hormone: bone growth genes are found on PAR regions, which are lacking
- Estrogen replacement: ovarian insufficiency leads to a lack of sex hormones
Describe what is happening in terms of gene expression and gene dosage in Klinefelter Syndrome
With Klinefelter Syndrome, there is an extra copy of all PAR genes gained on the X chromosome
- Increased gene dosage due to an extra X chromosome
What are the 8 characteristics of Klinefelter Syndrome?
- Tall stature with long arms/legs
- Weaker muscles
- Poor coordination
- Gynecomastia
- Learning disabilities
- Speech/language problems
- Infertility
- Hypogonadism/Androgen deficiency
