Bld 204 Exam 3 Genetic Disorders

Front 1

Lists the steps from DNA → PROTEIN

Back 1

DNA → (transcription) → mRNA →
(translation) → PROTEINS

Front 2

How do Genetic Disease Happen (2)

Back 2

Cengenital: present at birth
Herediatary: passed on genetically from parent
to offspring

Front 3

Genotype

Back 3

is what the genetics are, what the DNA code is
(our genome encodes a particular allele)

Front 4

Phenotype

Back 4

is the observable outcome of the code
(blue eyes, brown eyes)

Front 5

5 types of genetic abnormalities

Back 5

1. Somatic DNA mutations
2. Mitochondrial DNA mutations
3. Chromosomal Defects
4. Single gene mutations
5. Multifactoral disorders

Front 6

How do we analyze whole chromosomes?

Back 6

Karyotyping

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Karyotyping:
Sources of chromosomes: 5 steps

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1. lymphocytes, amniotic fluid, bone marrow
2. cells are encouraged to enter mitosis
3. chromosomes are separated from the cells
4. suspension is put on slide and giemsa stained
5. makes bands on chromosome that are used to define regions

Front 8

Karyotyping Analysis:
How do you identify regions with mutations: (4)

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1. Chromosome number
2. Short or long arm: p or q
3. Group that the band is in: numbers
4. Number of band in the group

Front 9

How common are major abnormalities:
______ % of human conceptions
______ % of spontaneous abortions
(_____% of pregnancies)

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6%
50%
15-20%

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Deletions:
You need to lose about 4000 _____ to make it visible

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kilobases
(that's a lot of genetic material)

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A type of deletion called Ring Chromosomes -

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breakages occur at both ends and the broken ends fuse (like string into ring/circle)

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Translocations:
Balanced: (2)

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-reciprocal transfer of segments between chromosomes
-CML translocation 9-22

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Translocation:
Robertsonian: (2)

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-one very large and one very small
-long arm of one and short arm of another

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Inversion:
Breaks and moving around occur in

Back 14

the same chromosome

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Inversion:
Paracentric -

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same side of the centromere

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Inversion:
Pericentric -

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opposite sides of the centromere

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Aneuploidy -

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-not a multiple of 23
-Trisomy: extra chromosome
-Monosomy: loss of a pair

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Polyploidy -

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-additional whole haploid set
-69 instead of 46

Front 19

Prenatal Testing for Genetic Disorders:
Screening examples: (2)

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-blood tests
-ultrasound

Front 20

Prenatal Testing for Genetic Disorder:
Diagnosis examples: (3)

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(chromosome testing)
-Chorionic Villus Sampling:
material from placenta
-Amniocentesis: amniotic fluid
-Percutaneous umbilical blood sampling:
umbilical cord blood

Front 21

Example of a syndrome for Autosomal Trisomy:

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Down's Syndrome (Trisomy 21)

Front 22

Down's Syndrome is most common
_______ disorder with ratio _____ in USA

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-cytogentic
-1:700

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-Down's Syndrome occurs more likely in
-______% have trisomy 21

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women who are 35 or older
95%

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Cause of Down's Syndrome is ______ ________

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meiotic nondisjunction

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Down's Syndrome Major Clinical Symptoms: (9)

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-visible symp: face, hands, long bones
-eye disease, -sleep apnea, -hearing loss
-cardiovascular: 40% have congenital defects
-Hematology: 10-20x risk of develop. leukemia
-Immune: ↑ susceptibility to infection
-CNS: reduced IQ, Alzheimer's like symp. in 40s
-Reduced life expectancy: late 40s

Front 26

Klinefelter's Syndrome:
-Extra...
-Nondisjunction...
-May have...
-Contributing factors: (2)

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-extra X chromosome in phenotypic male
-Nondisjunction leads to XXY
-May have more than one extra X
-Contrib. Factors: Advanced maternal age,
Radiation of either parent

Front 27

Clinical Features of Klinefelter's Syndrome:

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-Hypogonadism: too little testosteron,
under developed genitals
-↑ leg length, disportionately
-wide pelvis
-reduced facial/body hair
-Gynecomastia (risk breast cancer ↑)

Front 28

Single Gene Defects:
_____ known defects that cause disease

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~4000

Front 29

Single Gene Defects are either
______ or _______
______ or _______

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autosomal or sex-linked
dominant or recessive

Front 30

Frequency of Autosomal Dominant

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~2-9:1000 births

Front 31

What do you see in Autosomal Dominant (5)

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-parent affected
-↑ severity if homozygous
-phenotype is expressed at same rate in males & females
-see mutant phenotype in very generation
-both heterozygotes and homozygotes express
the mutant phenotype

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Penetrance -

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Proportion of individuals carrying a variant of a gene that express the associated trait

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Incomplete Penetrance -

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Individual with dominant mutant genotype presents a normal phenotype

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An example of Autosomal Dominant:

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Familial hypercholesterolemia:
-LDL receptor defect (LDLR) / can't remove LDL
-Premature atherosclerosis

Front 35

What do you see in Autosomal Recessive: (4)

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-parents may not have mutant phenotype
-parents are at least heterozygous
-penetrance is usually complete
-frequency of mutant phenotype for males
and female is equal

Front 36

An example of Autosomal Recessive:

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Phenylketonuria (PKU):
-defect in enzyme that breaks down phenylalaline
-build up and cause brain damage (can be treated by diet change)

Front 37

Another example of Autosomal Recessive:

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alpha1-antitrypsin deficiency

Front 38

alpha1-antitrypsin deficiency characteristics (3)
(autosomal recessive)

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-AAT suppresses proteases in lungs
-Without functional AAt, emphysema can result
-3 alleles: M,S,Z

Front 39

List 3 alleles of alpha1-antitrypsin deficiency:
(autosomal recessive)

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M: normal
S: produces a lower amount of AAT
Z: results in serious loss of AAT production

Front 40

Sex-Linked:
Sex Chromosomes are

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XY

Front 41

Sex-Linked:
Problems usually occur on the ____ chromosome.
Therefore what happens in males vs. female

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-X
-male: all it takes is 1 copy for expression of the
mutant phenotype
-female: need to be homozygous for the mutant
phenotype to be expressed

Front 42

X-Linked:
- From DAD...
- From Heterozygous MOM...

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-all daughters are carriers ; all sons are fine
-50% of sons are affects ; 50% of daughters are carriers

Front 43

An example of X-liked

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Hemophilia A:
-Factor XIII deficiency in coagulation pathway causes bleeding problems

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Fragile X Syndrome characterized by

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severe mental retardation and some distinctive physical characteristics

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Fragile X Syndrome acts like ______ ______
with _____ ______

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X-linked dominant ; incomplete penetrance

Front 46

In Fragile X Syndrome,
Phenotypically normal males can pass it on to
their __________

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grandchildren

Front 47

In Fragile X Syndrome,
Premutation -

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the initial change in the genome needs processing
through female meiosis before it is full expressed

Front 48

In Fragile X Syndrome:
Mutations involves _____ _____ repeats in
_______ untranslated region

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CGG triplet ; FMR1

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In Fragile X Syndrome:
-Normal # of repeats is ______
-Premutation level is _______ copies
-Gene becomes abnormally _______ = repressed

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- ~30 (6-54)
- 60-200 copies
- methylated

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In Fragile X Syndrome:
Males are the _____
Females are the ______

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-Transmitters
-Carriers

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In Fragile X Syndrome:
-Problems with Male
-Problems with Female
(later in life)

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-have neurodegenerative disease similar to Parkinson's
-have premature ovarian failure

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3 other Triple Repeat Disease:

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1. Huntington's Disease
2. Myotonic Dystrophy
3. Charcot-Marie-Tooth Disease

Front 53

-Four nucleotides are allowed for _____ combinations
-those combinations need to code for
____ amino acids and
stops ____ and starts _____

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-64
-20 ; 3 ; 1

Front 54

Gene Deletions:
Alpha-thalassemia -

Back 54

number of deletions relates to severity of disease

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Gene Deletions: Alpha-thalassemia -
-Normal ____ requires two pairs of __ _____ genes:
-Loss of 2 copies alpha =
-Loss of all copies =

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-Hgb ; alpha globin
- HbH disease
- hydrops fetalis

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In Partial Gene Deletion, part of the code is deleted but

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some protein may still be translated

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Whole Codon Deletions:
Good news -
Bad news -

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-Doesn't alter the reading frame
-you lose an amino acid → result improper folding
or affect funtion or be just fine

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Example of Whole Codon Deletions:

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Cystic Fibrosis

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Cystic Fibrosis -

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most common mutation is a deletion of one codon
for phenylalanine in the gene for a
chloride transporter (CFTR)

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Fusions

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unequal crossing over between nonhomologous chromosomes results in parts of two genes fusing

Front 61

Point Mutations

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substituion of one base pair for another in dsDNA

Front 62

We classify DNA nucleotides A,C,G,T into two classes:

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1. A and G are purines
2. C and T are pyrimidines (U replace T in RNA)

Front 63

A purine binds to a _______

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pyrimidine (AT, CG)

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Transition

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purine switched for a purine or pyrimidine for pyrimidine
(A for G ; C for T)

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Transversion

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Purine to pyrimidine or vice versa
(A for T ; C for G)

Front 66

So the results of a point mutation in

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a base pair substition, that could result in a new amino acid when mRNA is translated
BUT
due to degeneracy of the code for amino acids, only 1/3 of these sorts of mutations have this affect

Front 67

Missense in point mutations

Back 67

one base substitution results in different
amino acid in final protein

Front 68

Examples of missense situations:

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sickle cell anemia (glutamate to valine)
AAT deficiency (glutamate to lysine)

Front 69

Nonsense in point mutations
-example

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Mutation results in a premature stop codon
-beta thalassemia

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Stop Codon Mutations

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-stop codon changed to code for an amino acid
-results in protein that is translated on thru a region that should not have been

Front 71

Frame Shifts

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insertion or deletion of a single nucleotide