The protein that plays a
role in Marfan syndrome
is called fibrillin-1.
Marfan syndrome is
caused by a defect (or
mutation) in the gene
that tells the body how
to make fibrillin-1.
TGF-β
Autosomal Disorders
Trisomy 21 (Down Syndrome)
Most common, best
known Chromosome
know disease
Most
Common
cause of
moderate
mental
retardation
Congenital heart disease
Celiac Disease
5-fold increase in
the risk of
leukemia (GATA1
mutations) on the
X chromosome
Dementia-similar
to Alzheimer
disease (bAPP
gene on chr21)
47,XX or XY,+21 = 95%
Trisomy 18 (Edwards Syndrome)
wont make
it after a
year old,
Usually a
spontaneous
abortion
Trisomy 13 (Patau Syndrome)
wont make it after
a year old, Usually
a spontaneous
abortion
X and Y
chromosome
aneuploidy
Most common
defects in liveborn
infants XXY, XXX,
and XYY, these are
rare in
spontaneous
abortions
Turner
Syndrome
Most common in
chromosome
abnormality in
spontaneous
abortions
MOST COMMON Monosomy
for 45 X (Female)
Coarctation of the Aorta
(Narrowing of the Aorta)
Webbed Neck
Klinefelter
Syndrome
Male with an
extra X
Chromosome
Gynecomastia Excess development
of mammary grlands SOME but not
all
Infertility
47,XXY (Male)
Neurofibromatosis
(NF1)
Chromosome #17
Common
Autosomal
Dominant
disease
half the cases are new
SPONTANEOUS rather than an
inherited mutation - functions as a
tumor suppressor gene
Pleiotropic phenotype that
predisposes to benign and
malignant tumors of the nervous
system
Cafe au lait
spots, Six or
more spots
Nonmalignant peripheral nerve tumors
Autosomal
Recessive
- Cystic Fibrosis
1 child in 2,000
Chromosome #7
Tay-Sachs disease
Jews in the
North America
Neurological
disorder that
develops at 6
months
Lysosomal storage disorder
Inability to metabolize GM2 gangliosides
Occurs only in
Homozygotes or
Compound
Heterozygotes --
NEEDS 2 MUTANT
ALLELES
Autosomal
Dominant
Familial
hypercholesterolemia
(FH)
Populations of European and Japanese descent
Mutations in the low-density lipoprotein (LDL) receptor
premature coronary artery disease (CAD)
It's rare homozygous patients, but much more severe
X-Linked Recessive
Only affect males
phenotype
only expressed
in females that
are
Homozygous
Hemophilia A
lack of blood
clotting factor
VIII
X-Linked = Mental retardation
Daughters sons
HAVE A 50% chance
of the mutant X
Daughters ALL
carriers
X-Linked Dominant
Rett syndrome
MECP2, a
DNA-binding protein
known as
methyl-CpG-binding
protein 2
Only females,
Insidious
severe brain
disorder that
affects girls. It's
usually
discovered in
the first two
years of life
Hemoglobinopathies
Annotations:
A blood disorder (such as sickle-cell anemia) caused by a genetically determined change in the
molecular structure of hemoglobin
a-Thalassemias
Chromosome #16
Deletions
Two identical alleles
Results in mild
anemia and
microcytosis
b-Thalassemias
Chromosome #11
Point Mutations
Simple b-Thalassemia
Accounts
for the
great
majority
of patients
decrease in
the
abundance of
b-globin
mRNA
mRNAs-have
premature stop
codons due to
single nucleotide
substitution
(Gln39Stop)
β+ thalassemia
Polyadenylation
defect (Bad
Substitution
AAUAAA to
AACAAA)
Capping defect
(patient had A
to C
transversion)
Anemia
Hemoglobin Kempsey
- Point
Mutation -
Higher O2
Affinity
Sickle
cell
disease
Hb-S
mutation due to amino
acid substitution
hemoglobin
Normal
GAG to GTG
Sickle
Beta6 GLU --> VAL Sickle ---> Hb-S
First two years of life present with
anemia, failure to thrive,
splenomegaly, repeated
infections, and dactylitis
ARE the
most
common
SINGLE
GENE
diseases in
humans
causes
substantial
morbidity
Complex Thalassemias
remove the b-globin
gene plus one or more
other genes or the LCR
= 19 KB
HPFH
Deletions with in b-Globin do not cause
Thalassmia but result in the phenotype
termed the hereditary persistence of fetal
hemoglobin (HPFH)
benign condition
Hb F (a2g2)
compensates
for the absence
of Hb A
Williams Syndrome
Deletion of about
26 genes long
arm (q) of
chromosome 7