Clinical Cytogenetics For Gc Boards

Front 1

How long is G1 phase? S phase? G2? M Phase

Back 1

G1: 12 hours (interphase)
S: Duplication
G2: 3-4 hours (resting phase)
M: 1 hour

Front 2

Anaphase Lag

Back 2

One chromatid does not attach to spindle fiber, creates Monosomy

Front 3

When does nondisjunction occur?

Back 3

During Anaphase I

Front 4

Differences in outcomes between Meoisis I and Meoisis II

Back 4

In Meoisis II you have two identical copies of one chromosome

Front 5

Percent liveborns with anueploidy?

Back 5

0.3%
Leading cause of miscarriage
10-30% of fertilized eggs have a ch abnormality
20-25 % oocytes aneuploid
1-2% sperm aneuploidy

Front 6

4 Mechanisms of UPD

Back 6

1) Trisomy rescue
2) Gamete complementation - sperm missing chromosome, so fert egg is disomic for same chromosome
3) Monosomy rescue - duplication of monosomic ch
4) Somatic crossing over: result in UPD for segment on ch. (ie beckwith)

Front 7

Triploidy

Back 7

3 sets of ch. 1-3% preg
15-20% spont abortions that are ch normal
85% diadric (2 male, 1 female) 15% Digynic (2 female, 1 male)

Front 8

Diandric Triploid

Back 8

1 egg, 2 sperm
Empty egg fertilized by two sperm
None survive
well growth fetus
normal or small head
large placenta w appearance of partial hydatiform mole
3rd and 4th finger syndactyly

Front 9

Digynic triploid

Back 9

2 egg, one sperm
macrocephaly
placenta small and fibrotic
can survive to term and be liveborn > 1 yr
3rd and 4th finger syndactyly

Front 10

Hydatidiform Moles

Back 10

molar preg placenta has fluid filled sas (1-3 cm) from chorionic villa

Front 11

Partial Moles

Back 11

Fetus in early stages
Increased placental colume
Mixture of normal and hydropic villi: polyploid

Front 12

Complete Mole

Back 12

Fetus never present diffuse hydrops
Karyo is diploid (80% from dad 85% 46XY)
Empty egg fertilized by two sperm
risk 15-20 % degeneration into choriocarcinoma

Front 13

Benign Ovarian Teratomas

Back 13

46 XY karo usually all mat origin, abnormal development or primary oocyte (tumors have hair teeth etc but unorganized)

Front 14

Trisomy 21

Back 14

47, XX + 21
1/800 births
3-4% unbalanced Robertsonian (40-60% from Parent)
1-2% mosaics
24% survive to term

Front 15

Trisomy 13

Back 15

1/1200 births
CNS: deafness, seizures, apneic spells, holoproscencephaly microcephaly, micropthalmia, cleft lip,polydactyly
80% patau, 20% 13-14 translocation
55% parent of a carrier derivative 13:14

Front 16

Robertsonian Translocations

Back 16

1/1000, 5 acrocentric ch (13-15, 21, 22)
85% der (13, 14)(q 10,q10), 10% der (14, 21)(q10)(q10)
carriers at increase risk of infertility, unbalanced offspring, offspring UPD (90% isochromosomes )
0.6-0.8% if translocation involves non-homologous ch.

Front 17

Reciprocal Translocations

Back 17

~1/500- 1/1000
70% inherited, unique, risks hard to determine
20-25% parens with liveborn children
Size of segments matters: increased break point, smaller inbalance potential
Small distal segments : small imbalances, larger risks
large distal balances, decreased risks for liveborn abnormal child but increase miscarriage
11:22 common

Front 18

Pericentric Inversion

Back 18

Change at centromere

Front 19

Paracentric Inversion

Back 19

recombination at ends
90% inherited, genetically unstable
duplicated or deleted regions
almost always lethal

Front 20

Deletion Syndromes

Back 20

4p
5p
18q
18p
18q

Front 21

Marker chromosomes

Back 21

Supernumerary
Associated with abortion phenotype 13-16%
1/4000 newborns
80% from acrocentrics, 80% de novo
Isochromosome for p12 = Pallister Killian syndrome: in fibroblasts and not metaphase cells

Front 22

Parental sources of aneuploidy
13-15
16
18
21
XXY
XXX
monosomy x

Back 22

Parental sources of aneuploidy
13:15-87% Maternal, 208 % survive to term
16: 100% maternal, 0 survive
18: 95% maternal, 5.4% survive
21: 93%, 24% survive
XXY:55% maternal, 53% survive
XXX: 95% maternal, 95% survive
monosomy x: 8% PATERNAL, .3% survive

Front 23

Clinical FIndings that Suggest Mosaicsm

Back 23

-mild or variant phenotype
-streaks of pigmentation on the skin
-asymmetry

Front 24

Imprinted Chromosomes

Back 24

7: maternal UPD accounts for 10% of russell silver syndrome
11: patUPD 11 associated with beckwidth wiedemman syndrome
14: mat 14 UPD mild-moderate developmental delay, precocious puberty, scoliosis
14: pat 14 more rare, polyhydramnios, low birth weight, blepharophimosis, short palperbral diggures, small ears, small thorax, abnormal ribs, joint contractures, severe MR
MatUPD: >100 cases reported, associated with PW, can be hypopigmentations
Pat UPD 15: angelman

Front 25

Acrocentric Ch

Back 25

13-15
12, 22

Front 26

46 XX or XY t(11;22)(q11.2)

Back 26

recurring translocation
usually inherited
unbalanced segregants
risks for carriers ~3% for males and 5-7% for females

Front 27

Supernumerary RIng Ch

Back 27

1% of non-supernumerary rings are inherited, rest are denovo
most are inherited from Mom

Front 28

Marker Ch

Back 28

1/4000 newborns
80% from derived from acrocentrics, 40% from ch 15
20% familial
80% de novo and associated with maternal age effect

Front 29

XIST

Back 29

X inactivation region on X chromosome
important role in initiating and maintaining X inactivation
produces functional RNA and expressed in the inactive X chromosome

Front 30

PARS

Back 30

Pseudoautosomal Regions (PARS)
distal short arm of X and Y contain highly similar DNA sequences
Recombination happens often here

Front 31

Female vs Male Meoisis

Back 31

Males: begin puberty, duration of meosis is 60-65 days, 4 spermatids, 100-200 million/ej