HUMAN GENETICS
Disorders
Interpreting Pedigrees
with Andrew Douch
 Interpreting Pedigrees the Fast Way –Example 1(6:42)
 Example 2 (6:46)
1. Is anyone with a phenotype different from
parents?
2.Are there any girls with recessive phenotype
who have a father or son with a dominant
phenotype?
Autosomal Dominant
X-linked dominant
Autosomal Recessive
X-linked recessive
Autosomal Dominant:
trait does not skip generations
Autosomal Recessive:
tends to skip generations
X-linked dominant: both
males and females affected
does not skip generations
Affected sons have an affected mother
X-linked recessive: more
males than females affected
Skips generations: affected sons from
non-affected mothers
Testing for genetic
disorders
Ultrasound imaging-a sonogram made
from passing high-frequency sound waves
with a transducer through the abdomen
(least invasive)
Testing for genetic
disorders
Amniocentesis-a small amount of
amniotic fluid, which contains fetal tissues,
is sampled
Use cells for karyotyping
Testing for genetic
disorders
Chorionic villus sampling (CVS)-take a
sample of the placental tissue for
chromosomal abnormalities
Can use cells for karyotyping
AUTOSOMAL RECESSIVE
Autosomes = ,
chromosomes #1- #22
Cystic Fibrosis-ff
It causes the body to
produce a thick, sticky
mucus that clogs the
lungs and digestive tract.
On Chromosome 7
Autosomal
recessive
One test is for salty skin
CF salt test
Salty skin (Mutations
of the CFTR gene
affect functioning of
the chloride ion
channels)
thin (do not digest
well)
abnormal bowel
movements
CFTR video (8:18)
describe 6 mutation
disfunctions for 2 pts Ex Cr
Cystic Fibrosis (cont.)
Most common fatal genetic
disease in US today
Most common in Caucasians
 Small Child CR Treatment (thumping)
 Thumping Vest (1:24)
 Living with CF (3:48)
Daily meds
Cystic Fibrosis
 Chromosome 7
 FF = no CF
 Ff = carrier
 ff = has CF
 (recessive)
 Life with CF (3:48)
PKU
Phenylketonuria (PKU)
PKU on chromosome 12
recessive
Lacks enzyme to break
down the amino acid
phenylalanine (found in
milk)
PKU (cont.)
The breakdown products
can be harmful to
developing nervous
systems
Leads to mental
retardation.
 Kate with PKU Movie
PKU
Chromosome 12
Put on low protein
diet
Avoid
phenylalanine
TAY SACHS
Results in
degeneration of the
nervous system.
Chromosome 15
recessive
Highest rate in
Eastern
European
Jews, next
IrishAmericans
Tay Sachs (cont)
Lack enzyme to
break down fat,
accumulates in
brain (poisons it)
tt
Chromosome 15
 NOVA Online |
Cracking the Code
of Life | Watch the
Program Here #3
Tay Sachs Disease is a fatal lipid storage
disorder where a fatty substance
(ganglioside) builds up in the nerve tissue
and cells of the brain. This is caused by an
insufficient enzyme called betahexosaminidase A that catalyzes the
biodegration of gangliosides.
Tay-Sachs Symptoms
Symptoms first appear at 4 to 6 months
of age when an apparently healthy
baby gradually stops smiling, crawling
or turning over, loses its ability to
grasp or reach out, and eventually
becomes blind, paralyzed and unaware
of its surroundings. Death usually
occurs by age 4.
Tay-Sachs PT (1:52)
Albinism
Inability to
manufacture
pigments (melanin)
in skin and eyes
Autosomal
recessive trait
Chromosome 11
Albinism
Famous Albinos
Andy Warhol, a
famous artist
“The Twins” in
Matrix Reloaded
Rock musician
Edgar Winter, an
albino.
Is this an advantage or
disadvantage?
Different kinds of albinism
affect chromosomes 1, 9, 10, 11, 15
and X (ocular albinism)
Often rapid back and forth eye movement –
lack of pigment in eyes.
Polar bears actually
have black skin under
all that white fur.
AUTOSOMAL DOMINANT
on chromosomes 1-22
Sickle Cell Anemia
Autosomal
Found in AfricanAmericans
dominant disease
Chromosome #11
Red blood cells
collapse and clot
blood vessels
Sickle-Cells
Normal Red
Blood Cells-like
a donut
Sickle-cells
collapse, hard,
clog vessels
Sickle-Cell Anemia
Codominant
SS = disease
AS = carrier (somewhat resistant to
malaria)
AA =normal hemoglobin
Living with SSA
Plasmodium in
blood - malaria
Sickle-Cell Complications
1.pain episodes
2.strokes
3.increased infections
4.leg ulcers
5.bone damage
6.yellow eyes or jaundice
7.early gallstones
8.lung blockage
9.kidney damage and loss of body water in urine
10.painful erections in men (priapism)
11.blood blockage in the spleen or liver (sequestration)
12.eye damage
13.low red blood cell counts (anemia)
14.delayed growth
Huntington’s Disease
Woody Guthrie’s
disease (folksinger
1960’s)
Autosomal dominant
Does not manifest
itself until age 20’s 30’s
H=dominant disease
What is the chance of a child of a
Huntington Mother having
Hungtingtons?
Huntington’s
Chromosome 4
Atrophy of brain
Uncontrollable muscle
spasms
40+ CAG’s (build up
protein clumps)
 Huntington's Chorea Dance
(5:33)
Controls
thinking,
emotion,
movement
Huntington’s

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










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Clumsiness
Jaw clenching
Loss of coordination and balance
Slurred speech
Swallowing and/or eating difficulty
Uncontrolled continual muscular contractions
Walking difficulty, stumbling
Hostility/irritability
Inability to take pleasure in life
Lack of energy
person with Huntington's also may exhibit psychotic behavior:
Delusion
Halluciations
Inappropriate behavior (e.g., unprovoked aggression)
Paranoia
Achondroplasia
-Autosomal Dominant
-chromosome 4
Achondroplasia:
Genetic Causes
(2:40)
Achondroplasia
Dwarfism
Achondroplasia:
Genetics (2:20)
short stature
Dwarfism
shortening of limbs,
trident hands
prominent forehead
Average adult male
height of 52 inches;
average adult female
height of 49 inches
FAQ
Can short-statured
couples become the
parents of averagesize children?
AA=dead
Aa=Achondroplasia
aa=normal
A
A
a
a
FAQ
Can short-statured
couples become the
parents of averagesize children?
AA=dead
Aa=Achondroplasia
aa=normal
A
a
A AA
Aa
Aa
aa
X
a
Alzheimer syndrome
Widespread nerve
cell dysfunction and
cell death in the brain
Dementia (memory
loss)
 Alzheimer's Disease: Medical
Update (1:39)
 Life with Alzheimers
(3:56)
Alzheimer Syndrome
Autosomal Dominant
 Found on Chromosome 1,
or 10, or 14, or 19, or 21
 APO4, is a cholesterolcarrying protein linked to
development a protein that
forms plaque in the brain
 Alzheimer's neurology (1:01)
 Alzheimers' Disease: Neurology
Brain Loss
Early or mild stage:
 memory loss, especially of recent events
 difficulty in recalling names and conversations
 misplacing objects
 becoming lost in familiar neighborhoods
 repeating stories and conversations
 difficulty in learning new information
 personality changes
 decreased motivation and drive
 easily upset or anxious
Marfan Syndrome
autosomal
dominant
disorder
chromosome 15
Marfan’s: taller, pigeon
chest Marfan's Video (2:45)
Spidery fingers, enlargement of aorta
Michael Phelps Does
Not Have Marfans
Extra Tall Athletes
in their recruiting
physical are tested
for Marfans.
X
Clarence Holloway
of Louisville
does have Marfan's syndrome (had
Manute Bol did
Died at age 47
open-heart surgery)
Gheorge
Muresan
7’7”
Marfan Syndrome
a connective tissue
disorder
Affects skeleton,
lungs, eyes, heart and
blood vessels.
unusually long limbs
High arch palate
Debated if Abraham
Lincoln has Marfan’s.
SEX-LINKED DISORDERS
On X
chromosome
Hemophilia- “bleeder’s disease”
New Hemophilia Treatment (48 secs)
Living with Hemophilia (4:53)
Hemophilia blood tainted
with AIDS
60 Minutes:Hemophiliacs Sue the Blood
Donors Organizations
Hemophilia passed by
queen victoria
Blood does not Czar Nicholas
clot normally
royal family
Sex-linked
recessive
Missing AHF
(clotting
factor in blood)
Royal PedigreeHemophilia
“bleeder’s disease”
XHXh = female
carrier
XhXh = female
hemo
XHY = normal
male
XhY = hemo male
Color Blindness
inability to perceive differences
between some of the colors that
others can distinguish.
More common in males
Sex-linked (red and
Green) on
X chromosome
What it's like being color-blind? (3:35)
Color Blindness
3 seconds to
determine number
Ishihara Test for Color
Blindness
Ishihara
The individual
with normal color Test for
vision will see a 5 Color
revealed in the
Blindness
dot pattern.
An individual with
Red/Green (the
most common)
color blindness
will see a 2
revealed in the
dots.
 Are You color blind? (2:26)
Color blindness=can’t tell
certain colors
Recessive on X
chromosome = c
XCXc = normal
female (carrier)
XcY = color-blind
male
What numbers do you see?
Note: X and Y used
Need X and Y on Punnetts
Duchenne Muscular
Dystrophy
MD
Duchenne Muscular Dystrophy
On Xm chromosome
Weakens and degenerates
muscles
Found mostly in males
mutation in the dystrophin gene
DMD
absence of dystrophin, a protein that
helps keep muscle cells intact.
-Leg muscles first.
-Calves often enlarged.
-Eventually this
weakness spreads to
the arms, neck, and
other areas.
DMD
Onset ·Early childhood about 2 to 6 years.
 Symptoms ·
Generalized
weakness of muscle
Wasting affecting
limb and trunk
Duchenne Timeline
(5:43)
DMD
Survival rare
beyond late
twenties.
X-linked
recessive
(females are
carriers).
POLYGENIC DISORDERS
Determination of
disorder occurs on
more than one
chromosome
SPINA BIFIDA
is a fault in the spinal
column in which one or
more vertebrae (the bones which
form the backbone) fail to form
properly, leaving a gap or split.
A Snapshot of Spina Bifida (4:52) 
Spina Bifida
#6, #14 and others
Gap in spinal
column
Shunts often put in
the brain to drain
the fluid
Agent Orange
 Children with Spina
Bifida whose parent was
in contact with Agent
Orange during the
Vietnam War are
compensated
Cleft Lip/Cleft Palate
#11, #17, #22
A cleft is an
opening in the lip,
the roof of the
mouth (hard
palate) or the soft
tissue in the back
of the mouth (soft
palate).
Clefts
Bilateral Complete
Cleft Lip/Palate
Clefts occur more often among Asians and
certain groups of American Indians
than among whites.
They occur less frequently
among blacks.
Cleft lip/palate
As you can imagine
there are feeding
problems
#11, #22, #17 –
Polygenic
 Unilateral Cleft Lip Repair (9:15)
Hypercholesterolemia
polygenic dominant
is the presence of high levels of
cholesterol in the blood.
lead to atherosclerosis (hardening
of the arteries)
additive effects of multiple genes
(polygenic) yellowish patches
consisting of cholesterol
deposits above the
eyelids.
Hypercholesterolemia
On Y chromosome
SRY gene: male
determining only on Y
Testes
determining
factor
NOTE:
If you are born with no “X”
chromosome- it is fatal
If missing an autosome-it is
fatal
X chromosome
Sex-linked traits
Triple-X Syndrome
triplo-X
trisomy X
XXX syndrome
47,XXX aneuploidy
There is usually no distinguishable
difference to the naked eye
between women with triple X
and the rest of the female population.
Triple-X Syndrome
Although females with this condition may
be taller than average, this chromosomal
change typically causes no unusual
physical features.
Most females with triple X syndrome have
normal sexual development and are able
to conceive children.
Nondisjunction
Chromosomes
to segregate
unevenly
during meiosis
Mistakes in
Meiosis
Down’s Syndrome
Trisomy 21
Extra fold over
eye
Sluggish
muscles
Mental
problems
Trisomy 21 Karyotype
Nondisjunction
Turner’s Syndrome
Adults with Turner syndrome are short,
averaging around four feet, eight inches in
height.
Flap in neck
Small breasts
But girls with Turner syndrome
don't start life as very short
individuals - they become short
over time-do not develop
sexually
Turner’s Syndrome 45 X0
Kleinfelter’s 47 XXY
Kleinfelter’s
-Testes are small
-breast growth (gynaecomastia)
-poorly developed secondary sexual
characteristics.
Klinefelter’s
Men are sterile (no sperm).
Special Topics In Human
Genetics
BARR BODIES
When a female is
born one of her X
chromosomes is
inactivated = a
Barr Body (early
in embryonic
development)
Used to test
femaledness at
Olympics
So there is not
excess of X info
in females
Calico Cat – X linked
Only females
have 3 colors
(orange,
black, white)
Looks like
“Pepper”
Multiple colors in cats mostly
in females
GENETIC DISORDERS REFERENCE
SHEET:
Down Syndrome (Trisomy 21)
Edward's Syndrome (Trisomy 18)
Patau Syndrome (Trisomy 13)
Klinefelter Syndrome (47, XXY)
Turner Syndrome (45 XO)
Metafemale (46XXX)-taller
Autosomes (#1-22) so 44 if normal
Angelman Syndrome
Deletion of Chromosome 15
If inherited from FATHER
Symptoms: Short and obese, delayed
development, frequent laughing
Angelman Syndrome
Prader-Willi Syndrome
Deletion is
inherited from
mother’s
chromosome 15
Hyperactive,
chronic hunger,
low muscle
tone, obesity
Prader-Willi Syndrome
–Before and after controlled eating