Clinical cytogenetics

Question 1

3 common reasons for chomosomal studies

Answer 1

1. neonatal and peds - testsing
2. infert. and prenatal - 50% of aborts have abnormality
3. leukemia and lymphoma - diagnostic and prognostic

Question 2

def. chromatin

Answer 2

uncondensed DNA

Question 3

how is karyotype organized

Answer 3

by size and shape

Question 4

what type of cells must be used for karyotype

Answer 4

dividing

Question 5

what is G banding and result

Answer 5

technique where treat with 2 dyes and then get band pattern - most genes in light band

Question 6

what is nomenclature for Downs’ susndrom

Answer 6

47, XY, +21

Question 7

what are replication phases of meiosis

Answer 7

S phase - chomosomes replicate
prophase 1 - maternal and paternal chromos recombine
telophase 1 - chormosomes separate
M2 - sister chromatids separate - 4 gametes

Question 8

what is major cause of aneuploidy

Answer 8

nondisjunction

Question 9

what is result of non-disjunction at M1

Answer 9

2 x n+1

2 x n-1

Question 10

what is result of non-disjunction at M2

Answer 10

2x n
1 x n +1
1x n-1

Question 11

what is klinefelters

Answer 11

47, XXY

Question 12

2 causes of kline

Answer 12

1. non-dis in M1 of dad

2. non-dis in M2 of mom

Question 13

phenotype of klinefelter

Answer 13

• tall
• narrow shoulders
• small testes
• gynecomastia
• T def.
• azoospermia

Question 14

what is turner

Answer 14

45,X

Question 15

what is turner rare

Answer 15

very high rate of spont. abortions

Question 16

features of tri 18

Answer 16

mental ret, failure to thrive, sever heart defects, hypertonic, low set ears, short sternum

Question 17

features of tri 13

Answer 17

severe mental, poor gorwth, CNS malform,

Question 18

what is triploidy

Answer 18

3 sets of chromo

• dispermy common
• non-viable

Question 19

3 types of specimens for chromo analysis and how they must be treated and time periods

Answer 19

all at 37C

1. peripheral bloods - 72hrs
2. monolayer cell cultures - skin, abortus, amniotic fluid - 1 to 2 weeks
3. bone marrow or lymph nodes 1-24hr

Question 20

2 types of invasive prenatal testing

Answer 20

1. amnicenticis - 16-18wk - fine needle through abdo wall and into uterus
2. chorionic villus sampling - 10-12 weeks - cells from the developing placenta are tested instead of fluid through vagina or abdo wall

Question 21

5 indications for invasive testing

Answer 21

1. high risk preg
2. late maternal age
3. abnormal US
4. previous trisomy 21
5. carrier of a rearrangement
   6, fam Hx

Question 22

adv. and dis adv. of amnio over CVS

Answer 22

adv. - less miscarirgae, better chromo length, less mosaicism,
dis - done later

Question 23

when to suspect mosasicm

Answer 23

highly variable phenotype, can be hard to detect unless there are pigment variations

Question 24

what does 46,xx,del(18)(q23)dn mean

Answer 24

deletion of long arm of chromosome 18 new (denovo)

Question 25

why does a chromo deletion cause a defect

Answer 25

haplotype insufficiency - need enough - generally dose dependent

Question 26

what is cri du chat

Answer 26

5p deletion - as more is cut it become more severe

Question 27

types of rearrangments (5)

Answer 27

1. deletion 2. duplication 3. translocation 4. ring chromo 5. inversion

Question 28

can chromo rearrangment be inherited

Answer 28

yes

Question 29

what is reciprocal tranlocation and effect

Answer 29

switch of both ends of two different chromo - carrier is usally fine, but can them pass down and they are at risk for imbalance

Question 30

example of writing cytogenic translocation

Answer 30

46,XX, t(9;10)(p22;p15)

Question 31

what does breakpoint position determine

Answer 31

the amount of abnormality, the more that is switched, the less likely they are to be viable

Question 32

2 reproductive options for carriers of translocations

Answer 32

1. genetics - prenatal testing and can terminate preg | 2. fertility - donor egg or sperm

Question 33

how common are chromo abnormalityes at birth

Answer 33

rare - less than 1%

Question 34

what is CML translocation

Answer 34

somatic - in adulthood | - transfer ABL onto BCL gene - tyrosine kinase activity

Question 35

what is the cytogenic alternative to G-banding

Answer 35

FISH - used to detect abscence or presence of a particular sequence of chromos

Question 36

what are adv. of fish

Answer 36

- can detect low level mosaisicm - fast - specific - can do 100s at once

Question 37

what is a genomic disorder

Answer 37

small recurrent deletions or duplications | - happen frequently and distinct enough to call a syndrome

Question 38

what is size of genomic disorders

Answer 38

very small - too small to see with G banding | - need FISH or microarray

Question 39

what are segemental duplications

Answer 39

normal structure in chromo that are repeated mobile elements

Question 40

sig. of segmental duplications

Answer 40

- was evolotionary | - cause of possible genomic disorders

Question 41

def. non-homologous allelic recomb.

Answer 41

unequal crossing over that causes both deletions and duplications

Question 42

how to detect genomic disorders

Answer 42

microarray - 1000s of FISH at once

Question 43

what is degeorge

Answer 43

micro deletion 22q11.2 - truncus arteriosus - facial features - infection prone - variety of phenotype

Question 44

what is comparison syndrome of deletion duplication

Answer 44

dup. - william - cocktail party | del - speech delay, schizoid

Question 45

what is generally better

Answer 45

duplication

Question 46

how much of genome coded proteins

Answer 46

2%

Question 47

what are Canadian guidelines for child with dev. delay

Answer 47

genomic micro array - trio with child and parents

Question 48

what is Gbanding still first test for (4)

Answer 48

1. aneuploidy syndromes 2. sex chromos 3. suspected mosaicism 4. infet., multiple miscarriage

Question 49

see methodology chart

Answer 49

see

Question 50

what is impact of micro array on clinical genetics

Answer 50

1. improve diagnosis, treatment, prevention 2. discover new syndromes 3. insght into the genes and dev. pathways that lead to harm

Question 51

what is seen in normal people

Answer 51

high degree of copy number variants

Question 52

4 possible outcomes of microarray analysis and interpretation

Answer 52

1. normal or benign - harmless 2. patho or likely patho - trioanalysis reccomneded - known to cause problems 3. variant of unknown sig. - trioanalysis reccomend 4. unexpected finding -