Cytogenetics: Lect 20 and 21

Question 1

Classifying chromosomes:

Answer 1

1. total length of chrom
2. position of centromere
3. presence of satellites

Question 2

Chromosomal abnormalities:

2 types?

Answer 2

-account for a large number of spontaneous abortions.

• numerical
• structural

Question 3

Numerical chrom abnormalities:

Answer 3

• Euploidy (polyploidy): no. of chrom is in multiples of 23
  
  • Triploidy: 3 copies of each chrom (69) incompatible w/ life
  • Tetraploidy: 4 copies of each chrom (92) lethal
• Aneuploidy:
  
  • monosomy: loss of a chrom. Incompatible w/ life except Turner synd/monosomy X
  • trisomy: presence of additional chrom

Question 4

Chromosomal aneuploidy:

Answer 4

Autosomal trisomy

• trisomy 21 (Down synd)
• trisomy 18 (Edward synd)
• trisomy 13 (Patau synd)

Sex chrom aneuploidy:

• Turner synd (45,X)
• Klinefelter synd (47,XXY)

Question 5

Trisomy 21: Down syndrome

Answer 5

• 47, XY+21
• most common liveborn autosomal trisomy
• risk factor: incr. maternal age, incr risk of meiotic nondisjunction during oogenesis (Meiosis I)
• intellectual disability, short stature, depressed nasal bridge, upslanting palpebral fissures, epicanthal folds, congenital heart defects, changes similar to Alz disease at young age (gene factors for Alz is on chrom 21)
• seen in FISH and Karyotype

Question 6

Trisomy 18: Edward syndrome

Answer 6

• 47,XY,+18
• nondisjunction during oogenesis
• clenched fist, overlapping fingers, rocker bottom fee, congenital heart defects, low set ears, small lower jaw, microcephaly and intellectual disability.

Question 7

Trisomy 13: Patau syndrome

Answer 7

• 47,XX,+13
• nondisjunction during oogenesis.
• polydactyly, cleft lip/palate, microphthalmia, microcephaly, intellectual disability, cardiac anomalies.

Question 8

Sex Chromosme Aneuploidy:

1. Turner Syndrome:

Answer 8

• 45,X = no Barr body
• nondisjunction during meiosis
• X chrom monosomy, short stature, webbed neck, cystic hygroma at birth(neck swelling), primary amenorrhea, gonadal dysgenesis, streak ovaries.
• some cells are 45,X and others are 46XX and 47XXX (mitotic nondisj during embryogenesis)

Question 9

2. Klinefelter syndrome:

Answer 9

• 47,XXY; presence of Barr body
• nondisj during meiosis
• testicular atrophy, gynecomastia, female distribution of hair, infertility.
• may be caused by nondisjuc during meiosis I or II in mom or meiosis I in dad.

Question 10

Nondisjunction:

Answer 10

• most common in meiosis I females.

- indivs w/ Downs have 2 maternal chrom 21 and 1 paternal chrom 21.

Question 11

XYY fetus result of?

Answer 11

-meiosis II nondisjunc in dad

Question 12

XXX females result of?

Answer 12

-meiosis I or II in moms or meiosis II in dad.

Question 13

non-disjunction during embryonic development?

Answer 13

-occurs as a post-zygotic event.

Question 14

Structural chromosomal abnormalities:

Answer 14

• Balanced: no gain/loss of genetic material
• Unbalanced: gain/loss of genetic material.
• Translocations (reciprocal or Robertsonian)
• Deletions
• Inversions
• Ring chromosome
• Isochromosome

Question 15

Reciprocal translocation:

Answer 15

• exchange of genetic material between non-homologous chrom.
• in somatic cells, effects may transform to cancer and incr growth rate of cells or may be silent.
  
  • –ex: activation of an oncogene. Phil chrom t(9:22)>activation of ABl = chronic ML. Burkitt’s lymphoma= T(8:14).

-in germ line cells; higher incidence of spontaneous abortions in carrier.

Question 16

Robertsonian translocation:

Answer 16

• occurs btwn acrocentric chrom
• chrom 13, 14, 15, 21, 22
• loss of the short arms of the two chroms and fusion of the long arms.
• Alternate segregation: balanced chrom material (1 nl gamete and 1 carrier)
• Adjacent segregation: unbal chrom material (parital trisomy) on fertilization. (trisomy 14 “incompatible w/ life = spont abortion” and trisomy 21 ‘Down synd”).
• accounts for 2-3% of Down syndrome

Question 17

Microdeletion Syndromes:

Answer 17

• large deletions >4Mb; Wolf-Hirschhorn and cri du chat (detected by cytogenetic studies)
• small deletions

Question 18

Indications for Cytogenomic testing:

Answer 18

• deletion or duplication syndrome.
• Unexplained developmental delay or autism
• congenital anomalies/dysmorphic features.

-array CGH or SNP does not detect balanced rearrangements.

Question 19

Cri-du-Chat syndrome:

Answer 19

• deletion of chrom 5p
• high pitched cat-like cry, severe intellectual disability, speech problems, microcephaly.
• FISH and CGH for diagnosis

Question 20

22q11 Deletion syndrome

Answer 20

• Velocardiofacial/DiGeorge syndrome
• most common microdeletion disorder in humans
• microdeletion of chrom 22q
• congenital heart defects, absence of thymus, cleft lip/palate, prominent nasal root, learning disability, incr. risk for schizophrenia.

Question 21

Wolf-Hirschhorn syndrome:

Answer 21

• deletion of chrom 4p
• facial anomalies: widely spaced eyes, prominent nose, abnormal iris, cardiac anomalies, intellectual/development delay.

Question 22

WAGR syndrome:

Answer 22

• small-microdeletions;

- Wilms’ tumor, aniridia, GU malformations and retardation of growth and development.

Question 23

Deletions in chrom 15:

Answer 23

• Angelman: deletion of maternal chrom 15q11

- Prader-Willi: deletion of paternal chrom 15q11

Question 24

Inversions:

Answer 24

• may be pericentric (involves the centromere) or paracentric (does not involve the centromere).
• usually balanced & no clinical probs in carriers.
• result in change in banding pattern of chrom seen via Karyotype analysis.
• gametes w/ acentric and dicentric chrom are not viable.
• carriers of inversions may be asymptomatic but w/ high risk of spont abortions.

Question 25

Isochromosomes:

Answer 25

• loss of one arm of a chrom and duplication of the other arm
• results in chromosomal and gene dosage imbalance.
• in some children w/ Turner synd; w/ inactivated X isochrom.

Question 26

Ring chromosomes:

Answer 26

-forms when a chrom loses genetic material at the terminal portions and the ends fuse to form a ring like structure.