Transcript Human Genetic Disorders Power Point
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 imagin
g-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
well) (do not digest
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 Irish Americans
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 beta hexosaminidase 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 dominant disease Chromosome #11 Red blood cells collapse and clot blood vessels Found in
African Americans
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
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 average size children? A AA=dead Aa=Achondroplasia aa=normal a A a
FAQ
Can short-statured couples become the parents of average size children? AA=dead Aa=Achondroplasia aa=normal A A a
AA
X
Aa
a
Aa aa
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 cholesterol carrying 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
Manute Bol did Died at age 47 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 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 clot normally
Sex-linked recessive
Missing AHF (clotting factor in blood)
Czar Nicholas royal family
Royal Pedigree Hemophilia
“bleeder’s disease”
X H X h = female carrier
X h X h = female hemo
X H Y = normal male
X h Y = 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
The individual with normal color vision will see a 5 revealed in the 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)
Ishihara Test for Color Blindness
Color blindness=can’t tell certain colors
Recessive on X chromosome = c
X C X c = normal female (carrier)
X c Y = 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 X m 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