Genetic Disorders PPT

Genetic Disorders
2/11/2011 1
http://gslc.genetics.utah.edu/units/disorders/karyotype/

Causes
• A change in a gene called a
“mutation”
• A mutated gene = nonfunctional
protein or no protein at all
2/11/2011 2

What alleles are most
often affected?
• Most often recessive alleles (so not
expressed in heterozygous
individuals)
• Dominant alleles (rare)
2/11/2011 3

Characteristics
• Inherited at moment of conception;
programmed into one’s genes
• Sometimes treatable
2/11/2011 4

Genetic disorders
caused by dominant or
recessive alleles
2/11/2011 5

PKU (Phenylketonuria)
• (*most common among people
whose ancestors came from
Norway or Sweden)
2/11/2011 6

PKU cause
• Recessive disorder
• Individuals lack an enzyme that
converts one amino acid,
phenylalanine, to a different aa,
tyrosine
2/11/2011 7

PKU results
• Phenylalanine cannot be broken
down
• Its by-products accumulate in body
and result in severe damage to
CNS
• Mental retardation occurs
2/11/2011 8

Treatment
• PKU test performed on newborns
• PKU infants given diet low in
phenylalanine until brains are fully
developed
2/11/2011 9

New problem created
• When females who are
homozygous recessive for PKU
become pregnant
• High levels of phenylalanine in
blood can damage fetus
• Must avoid diet foods sweetened
with artificial sweetener containing
phenylalanine (diet pop, etc.)
2/11/2011 10

Cystic fibrosis
(CF)
• Autosomal Recessive
• Most common genetic disorder
among white Americans
• (1 in 20 w. Amer. Carries recessive
allele on chromo. #7)
• (1 in 2500 children born to w.
Amer. Inherit disorder)
2/11/2011 11

CF cause
• Defective protein in plasma
membrane
• (membrane channels for
transporting Cl- ions)
2/11/2011 12

CF result
• Accumulation of mucus in lungs
and digestive tract (favoring
bacterial infections)
• Difficulty breathing and digesting
food
2/11/2011 13

CF treatment
• Physical therapy, special diets,
new drug therapies have raised
avg. life expectancies of CF
patients
• Possibility of gene transfer?
2/11/2011 14

Tay-Sachs Disease
• Autosomal Recessive
• Causes progressive destruction of the
CNS
• Caused by the absence of an enzyme
called hexosaminidase A (Hex-A)
• Without this enzyme the GM2, a lipid
called ganglioside, accumulates,
especially in the cells of the brain,
causing a destructive process in the
fetus.
2/11/2011 15

Tay-Sachs Disease Cont’d
• The disease is not apparent until the
child is several months old.
• By the age of three or four, the CNS
is greatly affected and the body
cannot support normal functions
ending in death by the age of five.
2/11/2011 16

Tay-Sachs Disease Cont’d
• Slow development, loss of peripheral
vision, and abnormal startle response
• By the age of two most children have
seizures and diminishing mental function.
• Loss of skills – eventually can’t crawl, turn
over, sit, or reach out.
• Increasing loss of coordination,
progressive inability to swallow, and
breathing difficulties
• Eventually child becomes blind, mentally
retarded, paralyzed, and non-responsive
to his or her environment.
2/11/2011 17

Tay-Sachs Disease Cont’d
• Currently there is no cure
• Active research is occurring
• Replacement therapy for Hex-A is
being explored
• Bone marrow transplants have been
attempted but unsuccessful
2/11/2011 18

Huntington’s Disease
• Neurological disease
• Autosomal Dominant
• No current cure or effective treatment
• Causes gradual physical, emotional and
cognitive deterioration.
• Symptoms – involuntary jerking movements
of the limbs, face, and trunk; increasing
difficulty with communication, swallowing,
and walking; problems with planning,
organization, and initiating, as well as
personality change.
2/11/2011 19

Huntington’s Disease
• Disease normally strikes in the prime
of life (age 30-45) and possibly earlier.
2/11/2011 20

Genetic disorders
caused by sex-linked
genes (recessive)
• 1) color blindness
• 2) hemophilia
2/11/2011 21

Birth Defects
• A condition caused by an error in
the chromosomal make-up on an
individual
2/11/2011 22

Causes
• 1) Error in cell division:
Chromosomes line up, but are not
evenly divided during meiosis =
nondisjunction
RESULT? One too many
(trisomy: 47 chromosomes) or
one too few (monosomy: 45)
chromosomes in a cell
2/11/2011 23

Causes
• 2) translocation: breakage of an
arm of a chromosome – moves
and connects elsewhere
(1 in 500 egg or sperm cells)
Translocation video
2/11/2011 24

How are unusual #’s of
chromosomes detected?
• Karyotype:
sample of cells obtained from an
individual or fetus
Metaphase chromosomes are
photographed
Chromosome pictures enlarged,
cut apart, and arranged in pairs
according to length and location of
the centromere
2/11/2011 25

2/11/2011 27

Results of abnormal # of
chromosomes
• Most disorders of chromosome #
that occur in humans cause
symptoms so severe that the
developing fetus dies, often before
the woman even knows she is
pregnant
2/11/2011 28

Down syndrome:
trisomy 21
• Result of trisomy
(nondisjunction) or
translocation
• D.S. = 1 in 700 live births
• Trisomy Video
2/11/2011 29

Characteristics
• Mental retardation
• Short stature
• Slanting fold of skin on upper eyelid
2/11/2011 30
http://gslc.genetics.utah.edu/units/disorders/karyotype/

Unusual #’s of sex
chromosomes
• XO, XXX, XXY
• XYY
2/11/2011 31

Turner syndrome XO
• Females
• 1/6000 live births
• Absence of 2 nd sex chromosome
• External female organs, small and
nonfunctional ovaries, oviducts,
and uterus
• Don’t go thru puberty
changes=infertile
• Normal intelligence
• Monosomy Video
2/11/2011 32

Klinefelter’s syndrome
XXY
• Males
• 1/1500 live births
• Full life span, sterile,
underdeveloped testes and
prostate, no facial hair, breast
development, large hands and
feet, long arms and legs, slower to
learn but not MR
2/11/2011 33

Klinefelter’s syndrome
XXY
2/11/2011 34
http://gslc.genetics.utah.edu/units/disorders/karyotype/

Diabetes Mellitus
• Abnormally high blood glucose
concentration
• Autoimmune disorder where insulin
(lowers blood sugar level)
producing islet cells in pancreas
die
• May be caused by a disposition of
genes to an autoimmune
response—not really sure
2/11/2011 35

Diabetes (con’d)
• Genetic predisposition
• Triggered by viral infection????
• Type 1: onset during childhood,
daily injections of insulin
• Type 2: onset during adulthood,
more common than 1 and less
severe
Often correlated with obesity
2/11/2011 36

Spina Bifida
• Not genetic defect, but birth defect
• 1 out of 1,000 newborns
• Results from failure of spine to
close properly during 1 st month of
pregnancy
• Not lethal
2/11/2011 37

Galactosemia
• Rare genetic disorder
• 2 recessive genes
• Too much galactose in blood due
to missing enzyme that converts
galactose to glucose
• Accumulation is a poison to body
and can cause
Kidney failure, cataracts, brain
damage, enlarged liver
2/11/2011 38

Galactosemia (con’d)
• Diagnosis during 1 st week of life by
blood test
• Strict exclusion of
lactose/galactose from diet
2/11/2011 39

Genetic Counseling
• 1) Determine probability of genetic
diseases being carried and passed
on to children
Ex: pedigrees, chemical tests to
determine carriers
2/11/2011 40

Genetic Counseling
• 2) Diagnose the presence of a
genetic disorder in a fetus
• Median income for genetic
counselors with a master's degree
and up to 5 years experience in
2002 was $47,000 to $56,000.
• (http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genecounseling.
shtml#1)
• http://www.nsgc.org/careers/
2/11/2011 41

Amniocentesis
needle inserted into uterus and
10 mL of amniotic fluid is
extracted
beginning of 14-16 week of preg.
Genetic disorders detected from
presence of certain chemicals
Cells can be cultured and
karyotyped
2/11/2011 42