intro to medical genetics 1 and 2 -Mitsouras

Question 1

Define Metacentric, acrocentric, submetacentric

Answer 1

Metacentric: centromere located centrally
Acrocentric: centromere located in terminal position
Submetacentric: centromere located in intermediate position

satellites= very very small p arm

P arm=petit=short arm
q arm=long arm

Question 2

naming chromosomes

Answer 2

chromosome #, arm, region, band. sub band

ex: Xq32.1

regions start from the centromere –> out

Question 3

Turner Syndrome

Answer 3

45, X or 45, X0
Incidence is in 1: 2,500 five-born females
Features:
- Short stature
- Short metatarsals
- Widely spaced nipples & shield-like chest
- Loose skin at neck (webbing)
- No secondary sexual characteristics
- Sterile (gonads degenerate to connective tissue streaks at birth)
- Cardiac abnormalities (15%)
- Renal abnormalities
- Increased incidence of diabetes mellitus, inflammatory bowel disease
Can be detected by ultrasound in 2nd trimester as hydrops or nuchal cyst
Growth hormone administration to improve growth
Estrogen administration allows development of secondary sex characteristics

Question 4

Klinefelter Syndrome

Answer 4

47, XXY
Incidence is 1:1,000 live-born males
Features:
- Female body shape with gynecomastia in adolescence
- Female distribution of body hair
- Infertility
- Hypogonadism
- Low upper to lower body segment ratio (elongated limbs)
- Increased risk of osteoporosis & breast cancer
IQ & life expectancy same as for general population
Testosterone administration allows the development of secondary sex characteristics

Question 5

Trisomy 21=Down’s syndrome

Answer 5

47, XX, +21 or 47, XY, +21
Most common congenital chromosomal disorder associated with severe mental retardation
Incidence 1/800 live births (estimated) in US
Features:
- Craniofacial: brachycephaly, epicanthic folds, protruding tongue, small ears, upward sloping palpebral fissures, Brushfeld’s spots on the iris
- Limbs: single palmar crease (50%)
- Cardiac: atrial & ventricular septal defects, patent ductus arteriosus (45%)
- Mental retardation (IQ 40-45 but can be variable)
- Short stature
- Life expectancy usually 50-60 years (unless severe cardiac defects)

risk of having a child with Down’s syndrome increases with age—> 1/30 in 45 year olds —> due to an increase in non-dysjunction

Question 6

Trisomy 18

Answer 6

47, XY, +18

Question 7

FISH

Answer 7

Fluorescence In Situ Hybridization (FISH)
Takes advantage of hybridization of complementary nucleic acid sequences
Uses pt. metaphase chromosomes and fluorescently labeled probes
Visualized using fluorescence microscope
Fluorescent in situ hybridization (FISH)

analysis depends on the probe used: centromeric, telomeric, chromosome-specific (can use chromosome-specific simultaneously for ALL chromosomes)==> “M-FISH” or “SKY”

when a mixture of probes is used=chromosome painting.

Question 8

Array Comparative Genomic Hybridization (ACGH)

Answer 8

• Adaptation of microarray technique to detect chromosomal abnormalities
• Pt. and control DNA labeled with different fluorophores (green or red)
• Simultaneously hybridized to array containing probes covering the entire genome
• Compare the pt. DNA against the control to determine abnormalities.
• Yellow signal = [pt. DNA] = [control].
• If only the fluorophore for the control is observed = deletion in pt. DNA.
• If only the fluorophore for the Pt. is observed = gain of DNA in pt.
• Higher resolution than karyotyping and FISH (can detect even smaller rearrangements)
• CANNOT detect abnormalities NOT involving changes in amount of DNA (i.e. inversions & balanced translocations).
• Only gains and losses are detected.

Question 9

Trisomy 13: Patau Syndrome

Answer 9

47, XX, +13
47, XY, +13
Incidence is 1 in 5,000 live births (estimated)
 Features:
	-Seizures & hypotonia
	- Microcephaly & micrognathia, scalp defects (absent skin), cleft lip & cleft palate
-->failure to divide brain into 2 lobes 
	- Low set & abnormally shaped ears 
	- Polydactyly
	- Hernias
	- Cryptorchidism
	- Severe mental and motor retardation
	- Congenital heart defects (80%)
	- Dextrocardia (20-50%)
	- Holoprocencephaly (66%)
 Death by 1 month (50%) or 6 months of age (75%)
 Occurs more frequently with advanced maternal age

Question 10

Trisomy 18: Edwards Syndrome

Answer 10

47, XX, +18 or 47, XY, +18
Incidence is 1 in 5,000 live births (estimated)
 Features:
	- Micrognathia (small jaw)
	- Microphtalmia (small eyes)
	- Low-set ears 
	- Cardiac defects
	- Renal anomalies
	- Mental retardation
	- Generalized muscle spasticity
	- Rocker bottom feet
	- Clenched fist 
	- Intrauterine growth retardation
 Death by 1 year of age (90%)
 Occurs more frequently with advanced maternal age

Question 11

types of translocations

Answer 11

Translocation is the transfer of genetic material from one chromosome to another
Involves the breaking & exchange of chromosome fragments
- can be balanced or unbalanced
- can be Robertsonian or reciprocal
Unbalanced translocations involve the loss or gain of genetic material
Balanced translocations involve no loss or gain of genetic material
Reciprocal translocations involve breaking & exchange between 2 chromosomes and formation of 2 new derivative chromosomes (can be balanced or unbalanced)

Robertsonian translocations are a type of reciprocal translocation involving 2 afrocentric chromosomes–> only in chromosomes 13, 14, 15, 21, 22 (afrocentric chromosomes)

• if happens between 14 and 21–> familial Down’s syndrome
• a phenotypically normal parent with t (14q;21q) only has 45 chromosomes and can produce an offspring with an extra copy of 21 from t(13q;21q)

Carriers of translocations (parents) may be asymptomatic but may experience 
reproductive problems (infertility, miscarriage & having a child with an unbalanced chromosome complement)