Cytogenetic Disorders Flashcards
What is the name for cells that have multiples of 23 chromosomes?
What if it is 3n? 4n?
What situations could lead to these conditions?
Euploid
Triploid, tetraploid
dispermy, polar body fusion, meiotic failure
Why are monosomies often more severe than triosomies?
What is the usual cause?
The body can tolerate extra genetic material better than lack of it
the cause is nondisjunction in meiosis
What does the karyotype nomenclature
46,XY,del(4)(p14)
47, XX, +21
Male, deletion of band p14 on chromosome 4
down syndrome female
What is the occurrence rate of Down Syndrome?
What are defining features?
What increased health risks are associated?
What are the causes?
Chance of being passed on?
- Autosomal aneuploidy (trisomy 21) 1/800 to 1000 live births
- sandal gap, brush field spots in eyes
- digestive tract obstructions, leukemia, congenital heart defects (complete atrioventricular canal)
- 95% nondisjunction, rest are translocations
- risk of nondisjunction increases with maternal age
- males generally sterile;
- b/c 75% trisomy conceptions fail, risk is less than 50% for female to pass on
- germline mosaicism can be cause of recurrence in family
When does nondisjunction most often occur?
75% from meiosis I, rest from II
What syndrome is caused by trisomy 18?
Occurance rate?
Recognizable phenotype?
- Edward’s Syndrome
- 1/6000 births
- <5% survive to term
- Recognizable phenotype
- prenatal growth deficit
- prominent occiput
- clindodactyly, overlapping fingers with clenched fist
- short sternum, small mouth, short big toes
- Defects
- congenital heart defects
- omphalocele, diaphragmatic hernia, spina bifida
- 5% survive to 1 year
- developmental delay
What syndrome is caused by trisomy 13?
Occurance?
Defining features?
- Patau Syndrome
- 1/10,000
- 80% full trisomy, so trisomy of long arm only due to translocation
- Defining features
- oral facial cleft
- microphthalmia,
- postaxial polydactyly
- Defects
- malformations of central nervous system
- heart and kidneys are frequent
- 5% survive to 1 year
What is the genetic cause of Turner Syndrome?
What are its common features?
Is this seen in every cell?
monosomy X
45,X
short stature and/or amenorrhea
no, mosaicism is seen 45,X/46,XX and 45,X/46,XY
What is the name of the syndrome that occurs from 47,XXY?
How common is it? What are its characteristic features?
Klinefelter Syndrome
1/500 to 1/1000 male births
tall, disproportionately long limbs, hypogonadism, low testosterone, gynecomastia,
What are the characteris of trisomy X?
What are the characteristics of 47, XYY?
- Trisomy X
- some sterility, menstrual irregularity
- 90% from maternal nondisjunction
- 47,XYY
- taller than average,
- 1/30 in prison, most likely due to increased behavior disorders
- acne
What is uniparental disomy?
What impact does this have on disease occurrence?
- One pair of chromosomes derived from one parent, not both
- abnormal gametes from both, 2 + 0
- one abnormal 2 + 1, trisomy lost in embryo
- can lead the homozygosity for recessive or imprinting disordes
- about 30% Prader-Willi maternal disomy of 15
What is the difference between terminal and interstitial deletions?
What are 2 example of diseases caused by deletions?
Terminal = loss from end of chromosome
interstitial = loss from within chromosome
cri-du-chat and wolf-hirschhorn
Cri-du-Chat is caused by what deletion mutation?
What are the characteristic features of this syndrome?
Deletion 5p15.2
- cat-like wailing due to laryngeal defect
- growth delayed,
- hypotonia at birth,
- microcephaly
- round face,
- broad nasal root,
- epicanthic folds,
- down-slanting palpebral fissures,
- dysplasia ears,
- low IQ
What mutation is responsible for Wolf-Hirschhorn Syndrome?
What are the characteristic features of this syndrome?
Terminal deletion 4p
- growth retardation,
- microcephaly
- facial dysmorphism
- high forehead
- hypertelorism
- down-slanting palpebral fissures
- strabismus
- brod nasal root
- micrognathia
- low dysplastic ears
- defects cardiac, renal and central nervous system
- severe intellectual disability,
- 1/3 do not survive a year
What does it mean for chromosomal rearrangements to be balanced or unbalanced?
What are the 6 major types of chromosomal rearrangements?
Balanced means no loss or gain of material
unbalanced means gain or loss of material
- translocations
- duplications,
- deletions
- inversions,
- ring chromosomes,
- isochromosomes
What is the name for exchange of material between non-homologous chromosomes?
What 2 types can occur?
Translocation
- Reciprocal
- part of one chromosome transferred to another
- produces derivative chromosome
- meiotic segregation can lead to unbalanced rearrangement
- transfer can be unidirectional or bidirectional
- part of one chromosome transferred to another
- Robertsonian
- short arms lost, long arms join at centromeres
- viable forms involve 13, 14, 15, 21, 22
- arcocentric, short arms have no essential genes
- meiotic segregation can unbalance gamete
- alternate segregation, either translocation or two normal chromosomes to gametes
- adjacent segregation, all abnormal, some cause trisomy, some monosomy
What occurs to produce ring chromosomes?
Inversions?
Isochromosomes?
- Ring chromosomes
- ends lost, breaks join
- Inversion
- 2 internal breaks, join out of order
- pericentric- one break on each side of centromere
- paracentric- both breaks in one arm
- cross-overs can lead to duplication-deletion combinations in gametes
- 2 internal breaks, join out of order
- Isochromosomes- two copies of one arm
