W1: Genetic Disease

Question 1

Karyotype requires arresting cell cycle at ____ stage by using ___.

Answer 1

Metaphase, colchicine

Question 2

Define acrocentric.

Answer 2

Chromosome with centromere at one end, appearing to have only the q arm.
13,14,15,21,22

Question 3

Turner Syndrome is an example of monosomy/trisomy, affecting the __ chromosome.

Answer 3

Monosomy, X (only one copy)

Question 4

Translocation Down Syndrome is __% of all DS cases.

Answer 4

4%

Question 5

How does karyotype for Robertsonian DS look like? How many total chromosomes? 14? 21? Is it balanced?

Answer 5

Total: 46
14, 14+21 (attached), 21, 21
No, unbalanced

Trisomy DS, 46, X_

Question 6

How does karyotype for Robertsonian carrier look like? How many chromosomes? 14? 21? Is it balanced?

Answer 6

Total: 45
14, 21, 14+21
Yes, balanced

45, X_ (but normal because balanced)

Question 7

How does karyotype for nondisjunction DS look like? How many chromosomes? 14? 21? Is it balanced?

Answer 7

Total: 47
14,14,21,21,21
No, unbalanced

Trisomy DS, 47, X_

Question 8

What is the chance of a Robertsonian (RT) carrier passing down an unbalanced chromosome set that will cause RT DS?

Answer 8

1/3 (1/3 normal, 1/3 balanced; others lethal)

Question 9

How does FISH work and what does it detect?

Answer 9

FISH (fluorescence in situ hybridization)

Hybridize with section of chromosome to detect a specific position or a gene on intact chromosome; detects chromosomal numeric problems or rearrangements

resolution limited to size of probe

Question 10

What tests can be used to detect chromosomal anomalies?

Answer 10

Karyotype, FISH, chromosome painting

Question 11

What tests can locate Robertsonian carrier?

Hint: how many chromosomes will be detected?

Answer 11

Karyotype, chromosome painting
(not FISH because it’s balanced)

(detect 45 chromosomes)

Question 12

What tests can locate Robertsonian Down Syndrome?

Hint: how many chromosomes will be detected?

Answer 12

FISH, chromosome painting
(not karyotype because 46 chromosomes)

(46 chromosomes)

Question 13

What tests can locate nondisjunction DS (Trisomy 21)?

Hint: how many chromosomes will be detected?

Answer 13

Karyotype, chromosome painting, FISH

47 chromosomes

Question 14

Three types of Down Syndrome

Answer 14

Nondisjunction
Robertsonian Translocation
Mosaicism

Question 15

Robertsonian translocation for DS usually happens between chromosomes __ and __.

Answer 15

14,21

Question 16

Philadelphia Chromosome is caused by translocation between chromosomes __ and __; which can lead to ___.

Answer 16

9, 22;

CML (chronic myelogenous leukemia)

(Philadelphia Chromosome is balanced translocation but rearrangement activates pathway to CML)

Question 17

What tests can be used to detect Philadelphia Chromosome?

Answer 17

FISH, karyotype, chromosome painting

visualize spacial location of translocation

Question 18

Triploidy with extra paternal set leads to ___.

Triploidy with extra maternal set leads to ___.

Answer 18

Partial hydatidiform mole

early spontaneous abortion (SAB)

Question 19

Name 3 tests that can detect structural rearrangement of chromosomes

Answer 19

Detected by karyotype, FISH, chromosomal painting

Question 20

Name 3 presentations of Down Syndrome

Answer 20

• Hypotonia (low muscle tone)
• Dysmorphic facial features (flat nasal bridge, low-set ears,)
• Short stature
• Brachycephaly (“short”) with flat occiput (back of skull)
• Short neck, loose skin on nape
• Hands: short, broad, single transverse palmar crease
• Curved 5th digit
• Intellectual disability
• Congenital heart disease (1/3; least likely to survive)
• Increased risk for leukemia
• Premature dementia and onset of Alzheimer’s

Question 21

Heteroploidy includes euploidy and aneuploidy. Define them.

Answer 21

Euploidy - Xn multiples of haploid (ex. triploidy)

Aneuploidy - X+n (ex. trisomy)

Question 22

The most common inborn genetic disease in North America is ___.

Answer 22

PKU (inability to metabolize aa phenylalanine)

Question 23

Unusual features of autosomal dominant inheritance?

example of disease

Answer 23

1. reduced penetrance (people with genotype sometimes don’t express)
2. variable expressivity (severity and onset can vary)
3. high frequency of new mutation

Question 24

In Duchenne Muscular Dystrophy, usually male patients will present with ___ ___, very low muscle strength so need support of his arm to sit up.

Answer 24

Gower sign

Question 25

In women, __ __ __ can show up due to skewed x-inactivation, if the normal X-chromosome is inactivated early in embryonic life.

Answer 25

Duchenne Muscular Dystrophy

Question 26

Duchenne Muscular Dystrophy usually affect males/females because it’s a __ __ disorder.

Answer 26

Males; x-linked recessive

Question 27

Polymorphic markers in non-coding DNA are the basis of ___.

Answer 27

Fingerprinting These tests tell people apart, tell relationships RFLP – tedious; southern blot VNTR STR SNP – DNA sequencing

Question 28

Sickle cell disease, PKU, CF are examples of ___ ___ disease.

Answer 28

Autosomal recessive

Question 29

Variable penetrance and expressivity are associated with autosomal dominant/recessive traits.

Answer 29

Dominant

Question 30

Duchenne muscular dystrophy, color blindness, hemophilia A are examples of ___ ___ traits.

Answer 30

X-linked recessive

Question 31

In X-linked recessive traits, mothers/fathers usually pass the traits to their sons/daughters.

Answer 31

Mothers, sons

Question 32

hypophosphatemic rickets, incontinentia pigmenti are x-linked dominant traits, where only males /both males and females are affected.

Answer 32

Both ales and females

Question 33

How do you differentiate between x-linked dominant and autosomal dominant?

Answer 33

In x-linked dominant, males never transmit trait to male, but always transmit to daughter.

Question 34

Leber's hereditary optic atrophy, several myopathies are examples of ____ inheritance, where only mothers pass on the trait to offspring.

Answer 34

Mitochondrial (mi mutation affects skeletal muscle, brain, retina)

Question 35

What is an alternative for couple that wants to test for mutation in the fertilized egg without amniocentesis?

Answer 35

Preimplantation Genetic Diagnosis

Question 36

Fragile X is an X-linked dominant/recessive trait caused by mutation in the ___ gene.

Answer 36

Dominant, FMR1

Question 37

Penetrance with Fragile X Syndrome: What is the full mutation range for number of repeats?

Answer 37

Full mutation range: 200- >1000 repeats

Question 38

For trinucleotide repeat disorders where the length of repeat has to be measured, what are appropriate lab techniques to be used? Examples of diseases.

Answer 38

Southern blot, PCR; Fragile X, HD

Question 39

What technique is used to visualize the number of repeats in HD (diagnostic range?)?

Answer 39

Gel electrophoresis (40 repeats)

Question 40

List some direct mutation detection techniques

Answer 40

``` Southern blot (ID DNA specific sequence) Dot blot hybridization (ID DNA strand) PCR (amplify specific gene) DNA sequencing FISH ```

Question 41

What method is used to detect disease whose genes have not yet been identified?

Answer 41

Linkage analysis

Question 42

___ ___ ___ is a genetic disorder is the most common cause of mental retardation.

Answer 42

Fragile X Syndrome

Question 43

Both Fragile X Syndrome and Huntington's Disease are both ___ ___ disorder.

Answer 43

Trinucleotide repeat

Question 44

What tests are used to test for genetic diseases like Fragile X and HD?

Answer 44

Southern blot, PCR (trinucleotide repeat diseases)

Question 45

What does it mean when there is varied penetrance for HD? What is the ultimate number?

Answer 45

The presence of symptoms are determined by number of trinucleotide repeats. Above 40 repeats confirm diagnosis

Question 46

Define polymorphism.

Answer 46

existence of 2 or more alleles where the rare allele appears with frequency > 1% in the population

Question 47

Define SNP.

Answer 47

Single Nucleotide Polymorphism source of variance in genome (single base mutation in DNA)

Question 48

SNP usually occurs in coding/noncoding region of the genome.

Answer 48

noncoding

Question 49

Distinguish between mosaicism and chimerism.

Answer 49

mosaicism: mutation chimerism: fusion of fertilized zygotes during embryonic development both contain more than one type of genes