This is a review for the USMLE Step 1 of Genetics. It contains anything you need to know for your exam in pictures, diagrams and tables.

2. Gene
• Basic unit of inheritance
Locus
• Location of a gene on a chromosome
Alelle
• Variations of a gene
Genotype
• Alleles found at a locus
Phenotype
• Physically observable features
Homozygote
• Alleles at locus are the same
Heterozygote
• Alleles at locus are different
Dominant
• Requires only one copy of the
mutation to produce disease
Recessive
• Requires two copies of the mutation to
produce disease

3. G TCCATTTTAACG
ALA ILE LEU PRO
TA
MET
G TCCGTTTTAACG
ALA ILE LEU PRO
TA
MET
G TCCACTTTAACG
ALA ILE SER PRO
TA
MET
G TCCAGTTTAACG
ALA ILE STOP PRO
TA
MET
Normal
Silent
Missense
Nonsense

4. G ATTTTAACG
ALA ILE LEU
TA
MET
G TCATTTTAACG
ALA ILE LEU
TA
MET
G TCCAGTTTAACG
ALA ILE STOP PRO
TA
MET
Deletion
Insertion
Frameshift
Nonsense
G TCCGTTTTAACG
ALA ILE LEU PRO
TA
MET
TCC
PRO

5. G TCCATTGACGAC
GLN GLN LEU PRO
AC
GLN
G TCCATTGGCGGC
ARG ARG LEU PRO
GC
ARG
A TCCATTAAGAAG
GLU GLU LEU PRO
AG
GLU
Huntington’s
& Spinobulbar
muscular atrophy
Myotonic
Dystrophy
Fragile X
Friedreich’s
Ataxia
G TCCATTGTCGTC
LEU LEU LEU PRO
TC
LEU

6. RNA w/radioactive probe, sizes and
amounts of mRNA molecules for gene
expression
DNA Fragments w/radioactive probe on a
gel associated with a particular gene
DOT blot
DNA, RNA or Protein or
antibody. NO electrophoresis
required.
Protein w/radioactive
antibody, amounts of antigens
or antibodies

7. Arg
Trp
Cys
Glu
Asp
Lys
Asn
Gln
Thr
Pro
Ala
Gly
His
Tyr
Ser
Val
Met
Ile
Leu
Phe
Histidine
Tyrosine (PKU)
Serine
Valine (Sickle cell)
Methionine
Isoleucine
Leucine
Phenylalanine
Arginine
Tryptophan
Cysteine
Glutamic acid
Aspartic acid
Lysine
Asparagine
Glutamine
Threonine
Proline
Alanine
Glycine
5’3’
K
K

8. 1 2
1 2
3
6
1
4 53
542 7
3
6
1 2
I
II
III
IV
c
c
c c
c
Male
Female
Unknown sex
Affected
Dead
Autosomal R
carrier
X-linked carrier
Monozygotic
Twins
Mating
Consanguineous
Stillborn
SB
Dizygotic
Twins
SB

9. Autosomal Dominant
• Familial Hypercholesterolemia (LDL receptor)
• Huntington’s disease
• Marfan Syndrome
• Neurofibromatosis type 1
• Acute intermittent porphyria
• Retinoblastoma
• Myotonic Dystrophy
• Waardenburg
A a
a Aa aa
a Aa aa
50%
Dominant
Allele: A

10. Autosomal Recessive
• Sickle cell anemia
• Cystic fibrosis
• Phenylketonuria (PKU)
• Tay-Sachs disease (Hexoaminidase A)
• Hereditary Hemochromatosis
• Friedreich ataxia
A a
A AA Aa
a Aa aa
25%
Recessive
Allele: a

11. X-linked Dominant
• Fragile X Syndrome Dx: Southern Blot
• Hypophosphatemic Rickets
X Y
x xX xY
x xX xY
100% girls
0% boysA B
x Y
X Xx XY
x xx xY
50%
Dominant
Allele: X

12. X-linked Recessive
Obligate carrier
• Duchenne muscular dystrophy
• Lesch-Nyhan syndrome (HGPRT)
• G-6PD deficiency
• Hemophilia A and B
• Color blindness
• Menke’s disease
• Ornithine Transcarbamoylase (OTC)
• SCID (IL-receptor-y-chain deficiency{)
• Hunter’s disease
• X-linked Hyper IgM syndrome
X Y
X XX XY
x xX xY
50% for
the son
OBLIGATE CARRIERS are: Mother of affected son or Daughter of affected Father
Recessive
Allele: x

13. Mitochondrial
Subject to Heteroplasmy
• Leber Hereditary Optic
Neuropathy
• MELAS: Mitochondrial
Encephalopathy, lactic
acidosis, stroke-like episodes
• Myoclonic epilepsy with
ragged red muscle fibers

14. Genetic Variations
Variable Expression: Ex. Missense mutation
which can give SOME enzyme activity, unlike
nonsense
In NF-1 there could be variation in the
number and size of the tumors.

15. IncompletePenetrance
You know the person has the disease
genotype, but do not display phenotype.
Degree of Penetrance: Percentage of people
that show phenotype/symptoms
10% of the cases in Retinoblastoma
1 2
1 2 5
1
43
542 63
INHERITED RETINOBLASTOMA
Autosomal Dominant Disease
A A
a Aa Aa
a Aa Aa
50% multiply
by penetrance
90% = 45%

16. Pleiotropy
Single disease-causing
mutation affects
multiple organ systems
Examples: Marfan sx
Or Cystic Fibrosis
Thin,
elongated
limbs
Myopia
Lens Dislocation
Mitral Valve
Prolapse
Aortic
Aneurysm

17. Locus
Heterogeneity
Same disease phenotype
with mutations at different
loci
Ex. Osteogenesis Imperfecta
Mutations in chromosome
7 or 17

18. Delayed Age of Onset• Acute
Intermittent
Porphyria
• Huntington
Disease
• Hemochromatosis
• Familial breast
cancer
People who carry the disease mutation do NOT manifest the
phenotype until later in life.
Ex. Huntington disease (Autosomal Dominant)
Pt will develop symptoms until he/she is 40-50 years old

19. Anticipation
Most recent generations develop disease at earlier age or
greater severity.
Disease with Trinucleotide repeats such as:
• Huntington’s disease
• Fragile X syndrome
• Myotonic dystrophy
• Friedreich ataxia
RNA polymerase makes TOO many copies of the same
nucleotide.
Numbers under pedigree symbols are Age
of Onset and (CAG repeats)

20. • Proportion of each genotype in a population
• We can utilize Southern Blot
Genotype
Frequency
• Proportion of chromosomes that contain a specific allele in a
population.
• For X-linked diseases is equal to the number of affected males
in the population.
Allele Frequency
Genotype Count Genotype
Frequency
1-1 49 49%
1-2 42 42%
2-2 9 9%
TOTAL 100 100%
Genotype Count How many
copies?
1-1 49 2 of 1
1-2 42 1 of each
2-2 9 2 of 2
TOTAL 100 200
(2x49) +42
200
42 + (2x9)
200
= 0.7
= 0.3

23. Chromatid
Chromosome

25. Disease Cardiovascular Abnormalities
Down Syndrome Endocardial cushion defects (eg, ostium
primum atrial septal defect, regurgitant
atrioventricular valves)
DiGeorge Syndrome Tetrallogy of Fallot
Interrupted aortic arch
Friedreich Ataxia Hypertrophic cardiomyopathy
Kartagener Syndrome Situs inversus
Marfan Syndrome Cystic medial necrosis (aortic dissection
and aneurysm)
Mitral valve prolapse
Tuberous Sclerosis Valvular obstruction due to cardiac
rhabdomyomas
Turner Syndrome Aortic coarctation
Bicuspid aortic valve

26. Reciprocal.- They exchange pieces
with each other.
This is a balanced alteration.
It may give rise in offspring to Partial
trisomy or partial monosomy
(50% normal phenotype – 50% affected)
Robertsonian.- They get stuck together, it
can only happen between acrocentric.
This is a balanced alteration.
It may give rise in offspring to Trisomy or
Monosomy – specially with adjacent segregation.
(33% normal phenotype – 66% affected – 1 alive)Important Reciprocal Translocations
9:22 Philadelphia Chromosome (CML)
8:14 Overproduction of myc (Burkitt’s)
Usually lost
fragment
5% of Down syndrome pts are the result of this

27. Microdeletion
Interstitial: Prader-Willi
syndrome (Chromosome 15)
Terminal: Cri-du-chat
syndrome (Chromosome 5)

28. Fluorescence In Situ Hybridization (FISH)
DNA segment labeled with a fluorescent tag to create a
probe and find the locus of a gene.
Good to identify small deletions on chromosomes.
Spectral Karyotyping
It uses five different fluorescent probes.
Each chromosome is painted with a specific color.
Good to identify translocations.

33. Oncogenes Tumor Suppressor Genes
Involved in promoting cell
growth
Involved in controlling cell
proliferation
Mutation gives gain of function Mutation gives loss of function
One copy (one hit) is sufficient Both copies (two hits) are
necessary

34. GAATTC GAATTC GAATTC
GAATTC GACTTC GAATTC
RFLP. EcoR1 might cut palindromes in the
population, but in others, there is a
sequence variation. RFLP detects this.
VNTR. Detects differences between
population’s number of tandem repeats in
between two restriction sites.
TGTGTGTGTGTG
TGTGTGTG
STR. It’s like VNTR but smaller. We detect
them by PCR
A C C G T C C G
A C C C T C C G
SNPs. They detect single nucleotide
differences by DNA sequencing or ASO
probes.

35. Recombination
Frequencies
The closer the two linked loci are, the
lower the recombination frequency will be.
For Linked Loci: 1 centimorgan (cM) = 1%
recombination frequency
1 cM = 1 million base pairs
For this pedigree, only ONE out of 6 is
recombinant, so frequency in this family is
1/6 or 17%.
If LOD score greater than 3 = linked
If LOD score less than 2 = No linkage
Anything in between = incomplete

36. Mutation
Direct diagnosis: Mutation itself is examined.
WE KNOW THE LOCATION of the mutation.
Mutation
Indirect diagnosis: Linked markers are used to identify
the chromosome segment w/ the inherited mutation.
Marker
RFLP
VNTR
STR
SNP
PCR
ASO
RFLP (sometimes)
DNA Sequencing
DNA Chip

39. Gel Electrophoresis
1. Positive pole is on top, so
negative molecules will go up.
2. The longer the molecule, the
higher it will be.

40. 1 2
4
1 4
1
32
31
2
2
3
65 (37)
55 (40)53 (39)
40 (44)
1 2
4
2
1
1
3 52 6
1,2
1,2
1,2 1,2
2,2
1,1
1,11,1 1,11,1