CMMB 413 chapter 6

Question 1

Autosomal Chromosomal disorders

Answer 1

-gene dosage

Question 2

Sex chromosomal disorders

Answer 2

• involved in sex determination

- subject to different forms of genetic regulation

Question 3

Microdeletions and how to detect large deletion

Answer 3

• small regions deleted rather than big portions
• Large deletion: karyotyping (costs the least), FISH, CGH= MORE EXPENSIVE
• small microdeletions: PCR

Question 4

Trisomies in which 3 chromosomes and why

Answer 4

21, 18, 13; are the most gene poor

Question 5

Down Syndrome

Answer 5

1/800 births
associated with increased maternal age 
100% btw MZ twins 
100% discordance btw DZ twins and other family members 
karyotype 47XX/Y, +21

Question 6

Down Syndrome Phenotype

Answer 6

-hypotonia: poor development of muscles
-low set ears
-flat nasal bridge
-open mouth, protruding tongue
IQ~30-60
1/3 liveborn infants have congenital heart disease
15X increased risk leukemia
increased risk of heart disease

Question 7

DS Causes (5)

Answer 7

95% trisomy= chromosome 21 not the entire 21 
4% Robertsonian Translocation
21q21q Translocation 
Mosaic Down Syndrome 
Partial Trisomy

Question 8

recurrence risk

Answer 8

6 possible gametes, 3 are viable and of those 1/3 theoretical chance that the progeny are trisomic

mother carrier: 10-15% of progeny trisomic
father carrier: ~3% of progeny trisomic

Question 9

21q21q Translocation

Answer 9

isochromosome

Question 10

Testing for DS

Answer 10

biochemical screening; Ultrasound (thickness in neck); amniocentesis; chorionic villus sampling

Question 11

Mosaic Down Syndrome

Answer 11

• 2% of patients
• wide variability of phenotypes: depends on when mosaic occurs; earlier it happens in the development you see more phenotypes

Question 12

Partial Trisomy

Answer 12

very rare
duplication of part of 21q
very small!!

Question 13

Chorionic villus sampling

Answer 13

placenta is embryonic tissue so for this test you have to take cells from it
-can do this 10-12 week period

Question 14

When to use prenatal diagnosis

Answer 14

if the risk that the child has DS outweighs the risk that the procedure will lead to fetal loss (family history or age factor)

Question 15

Amniocentesis

Answer 15

sampling the amiotic fluid can use different techniques like CGH to test for the disorder
-can be performed at 14 weeks

Question 16

Trisomy 18

Answer 16

1/7, 500 births; survival>3 months rare 
60% patients females 
older maternal age
can be trisomic, translocation, or mosaic 
95% are aborted before they are born

Question 17

Trisomy 18 Phenotype

Answer 17

mental retradation, failure to thrive 
severe heart deformations 
receding jaw 
hypertonia (extreme muscle tone) 
clenched fist; fingers 2&5 overlap 3&4 
rocker bottom feet

Question 18

Trisomy 13

Answer 18

• very rare, 1:15-25000
• 1/2 of patients die in 1st month
• maternal age factor
• nondisjunction at M1
• unbalanced translocation
• cleft lip
• polydactyl (extra finger)

Question 19

segmental aneusomy

Answer 19

deletions that give rise to clinically recognizable syndromes

Question 20

contiguous gene syndrome

Answer 20

deletion of many continuous genes leading to haploinsufficiency

Question 21

Autosomal Deletion Syndromes

Answer 21

1/7000 births; cytogenetically visible

deletion regions have many genes

Question 22

Cri du Chat

Answer 22

deletion of a portion of chromosome 5

1% of all institutionalized mentally retarded patients

Question 23

Testes Determining Factor

Answer 23

• first signal deciding sex

- SRY gene: encodes a transcription factor

Question 24

Unusual Recombination of X and Y

Answer 24

X and Y outside of the pseudoautosomal region can result in an XX MALE and an XY FEMALE
SRY gene on an X chromosome= testis formation
XX males are not fertile because they dont have the AZF gene (no sperm production)

Question 25

X and Y pairing during meiosis

Answer 25

pseudoautosomal regions= only place where they can recombine= only place that is homologous

Question 26

X chromosome

Answer 26

has many genes that are used in males and females

Question 27

X inactivation

Answer 27

random inactivation of one X in females
-heterochromatic (Barr Body)
once an X chromosome is inactivated all daughter cells have the same X inactivated

Question 28

how is the X chromosome inactivated?

Answer 28

by jumbling up into heterochromatin and remain inactive

Question 29

How are Xi genes inactivated

Answer 29

inactivated by methylation and/ or histone modification

Question 30

what % escapes inactivation

Answer 30

10%

Question 31

XIST

Answer 31

• inactive X specific transcript (not completely inactivated some loci still expressed)
• only expressed from inactive X chromosome
• encodes noncoding RNA that doesnt leave the nucleus

Question 32

Sex chromosome Abnormalities

Answer 32

• most common of all genetic disorders

- less severe phenotypes than similar autosomal aneuploidies

Question 33

four most common syndromes

Answer 33

a) Klinefelter Syndrome (47,XXY)
b) 47, XYY Syndrome
c) Trisomy X (47, XXX)
d) Turner (45, X)

Question 34

Klinefelter Syndrome Phenotypes

Answer 34

-tall, thin
-long legs
-hypogonadism
-underdeveloped secondary sexual characteristics
-gynecomastia
-infertile
-low androgen
-one X chromosome inactivated
-gene dosage: higher dosage of genes that arent inactivated
XXY= phenotypically male with feminization ( development of breasts)

Question 35

47 XYY (When does non-disjunction happened?)

Answer 35

M2

Question 36

Trisomy X (47, XXX)

Answer 36

not abnormal phenotypically 
most undiagnosed
usually fertile 
70% have learning problems 
more X chromosome= more severe phenotype

Question 37

Turner Syndrome (45 X)

Answer 37

-short stature
-gonadal dysgenesis
webbed neck
-broad chest, widely spaced nipples
-normal intelligence
-99% of 45,X fetuses abort spontaneously