Genetics
Human Genetics
The Chromosomal Theory of
Inheritance, 1902
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Walter Sutton, Theodor Boveri, and others
independently noted parallels between
Mendel’s factors and chromosomes
Mendelian factors are located on
chromosomes, it is the chromosomes that
segregate and assort independently
Evidence of Mendel’s
Factors
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Drosophila melanogaster
Thomas Hunt Morgan
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First to trace a gene to a specific
chromosome
(white eyes to X chromosome)
Sex-linked gene
Linked Genes
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genes located on the same chromosome
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complete linkage
incomplete linkage
tend to be inherited together
do not assort independently
will not produce expected results
(ex. 9:3:3:1)
Linked Genes
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completely linked genes
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offspring express only parental types
incompletely linked genes
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offspring express mostly parental types
Experiment Regarding linkage between two genes (Dr. Morgan)
Body color
b+ = gray
b = black
Wing size
vg+ = normal
vg = vestigial
Conclusions
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Morgan reasoned that body color and wing
shape are usually inherited together because
their genes are on the same chromosome
Unlinked Genes
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genes located on different chromosomes
assort independently
completely linked
will produce expected results
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(ex. 9:3:3:1)
incompletely
linked
unlinked
openlearn.open.ac.uk
Pea plants: Gene locus of the 7
characters studied by Mendel (2n = 14)
1
Flower color and seed color
2
3
4
Flower positioning, Pod shape and plant height
5
Pod color
6
7
Seed shape
Crossing Over
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crossing over between 2 genes is directly
proportional to the distance between them
crossing over is more likely to occur between
genes that are far apart than those close
together
Map unit
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Centimorgans = map units
distance between genes
used to construct genetic maps
Human Genetics
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Two procedures for fetal testing
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amniocentesis
chorionic villi sampling
Amniocentesis
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14-20 weeks
several weeks for
karyotype
through belly
risk
Chorionic Villus Sampling (CVS)
*8-12 weeks
*24 hours for karyotype
*through cervix
*risk
*faster karyotyping
extracts a sample of fetal
tissue from the chorionic
villi of the placenta
This technique is not
suitable for tests
requiring amniotic fluid
Alterations of Chromosome Structure
Aneuploidy
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a chromosomal aberration
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monosomic
trisomic
Monosomics
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lost one autosome = lethal
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lost one sex chromosome = survive (XO)
Trisomics
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extra autosome
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13, 15, 18, 21, or 22
extra sex chromosome
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XXY, XYY, XXX
Autosomic Aneuploidies
Down Syndrome
J. Langdon Down (1866)
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physical characteristics:
epicanthal eye fold
simian crease on palm
single crease on little finger
wide nasal bridge
large protruding tongue
Incidence of Down Syndrome
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Incidence: 1/700 in US
incidence increases with increasing maternal age
www.alznyc.org/newsletter/spring2007/images/graph.jpg
Down Syndrome Types
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trisomy 21 (most)
translocation (some)
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21st chromosome translocated (21/21 & 14/21 & 9/21)
mosaic trisomy 21 (few)
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milder form
believed that fetus contains 47 chromosomes but loses one in
some cells
Cause of Down Syndrome
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Nondisjunction
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failure of chromosomes to separate properly in
meiosis (gametogenesis) or mitosis
Nondisjunction
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Problems with the meiotic spindle cause errors in
daughter cells
tetrad chromosomes
do not separate
properly during
meiosis I
Alternatively, sister
chromatids may fail
to separate during
meiosis II
Sex Chromosomal Aneuploidies
 Y Chromosome
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few genes
hairy pinna
webbed toes
SRY gene
sex-determining
region of Y
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cas.muohio.edu
en.academic.ru/pictures/enwiki/67/Celldeath.jpg
Presence triggers testis development
Absence triggers ovaries development
X Chromosome
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Genes (X-linked disorders)
Red-green colorblindness
hemophilia (royal)
Sex-linked Disorders
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Affect mostly males
Most are due to
recessive alleles
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Example: red-green color blindness
A male receives a single X-linked allele from his
mother, and will have the disorder, while a female has
to receive the allele from both parents to be affected
Hemophilia
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plagued the royal families of Europe
X chromosome
Queen Victoria
Alice
Xx
X= normal
Grand Duke Louis IV
of Hesse
x = carrier
XX Nondisjunction Oogenesis and
Spermatogenesis
 XXX
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metafemale, trisomy X
1/500 to 1/1000 female births
limited fertility
usually normal in other respects
XXY
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Klinefelter syndrome
1/2000 births
sterile
male sex organs but abnormally small
high-pitched voice
subormal-normal intelligence
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feminine body contours
(poor beard growth, small testicles,
partial breast development)
XYY
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do not exhibit a well defined syndrome
tend to be tall
XO
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Turner Syndrome
1/2500 female births
sterile
short stature
low-normal mental range
webbed neck and low-set ears, constriction of
the aorta, poor breast development,
underdeveloped ovaries
YO
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Inviable
at least one X needed for survival
YY Nondisjunction Oogenesis and
Spermatogenesis
XYY
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extra Y
1/1000 male births
fertile
normal appearance
Genetic Disorders
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Not equally distributed among various human
populations
some are lethal soon after birth others are lethal
later in life
Genetic Disorders Examples
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Cystic fibrosis (CF)
Sickle-cell disease
Tay-Sachs disease
Hemophilia
Huntington’s disease
Cystic fibrosis (CF)
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defect: failure of Cl- transport protein
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Behaves as a recessive genetic disorder
codominant: heterozygotes produce both normal cells
and abnormal cells with missing transport protein
symptom: thickening of mucous causes mucous
clogging, excess mucous in lungs, GI tract, liver,
increases susceptibility to infections, death in infancy
unless treated
most common fatal genetic disorder among whites
test available for carriers
Sickle-cell
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defect: abnormal hemoglobin crystallizes and sickles
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Behaves as a recessive genetic disorder
codominant disorder at molecular level because
heterozygotes produce both normal red blood cells
and sickle cells
symptom: poor blood circulation, sickled RBC damage
tissues
most common inherited disease among AfricanAmericans
test available for carriers
Huntington’s disease
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defect: inhibition of brain cell metabolism
dominant, late-acting gene
symptom: gradual brain cell deterioration,
uncontrollable movements, strikes in middle age
test for gene presence on 4th chromosome
Genomic Imprinting
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Identical alleles do not always have the same effects
on offspring
depends on which parent passed it along
example 1: Deletion on 15th chromosome
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maternal deletion:
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Angelman Syndrome - uncontrollable spontaneous laughter,
jerky movements, other motor and mental symptoms
paternal deletion:
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Prader-Willi syndrome - Mental retardation, obesity, short
stature, unusually small hands and feet
Genomic Imprinting: example2
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Fragile X syndrome
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Hereditary mental disorder
Tip of chromosome hangs
by a DNA thread
Addition of nucleotides near
the end of an X chromosome
If X is inherited from mother,
leads to mental retardation
If X is inherited from father,
child is normal
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medicineworld.org
The End