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GENETICS | 1

Gene/ Protein/
Oncogene/
Chromosome

Disease

Things to remember

SYNUCLEIN Protein
and
PARKIN Gene
Mutation

Alpha Synucleinopathy

Associated with:
Parkinsons disease (a.k.a.
Paralysis Agitans)
e.g. Michael J.Fox, Muhammad Ali,
Freddie Roach
Four motor symptoms:
1. Unilateral Resting tremors
(pill-rolling of hands)
2. Cogwheel/Leadpipe rigidity
3. Bradykinesia/ Akinesia
4. Postural instability (stooped
posture)

PINK 1 Gene

Juvenile Onset
Parkinsons Disease

Mask-like face
Small handwriting
(micrographia),
dementia
Decreased
blinking
Hypophonia
Shuffling gait
Fall: the MC
problem in
Parkinsons

Lack of Dopamine in pars


compacta neurons of the Substantia
Nigra
Tyrosine: the amino acid precursor of
dopamine
Levodopa + Carbidopa, Selegiline,
Rasagiline
COMT inhibitors (entacapone,
tolcapone)
Anticholinergics (trihexyphenidyl,
benztropine)
Amantadine
Haloperidol: the MC drug that causes
Parkinsonism Haldol shuffle
(Antidote: Biperiden(Akineton))
Accumulation of Lewy Bodies
Multiple System Atrophy (MSA)

ADINOPECTIN

An anti-inflammatory
cytokine

ALK protein
Anaplastic lymphoma
kinase
t(2:5)

Anaplastic large cell/ null


cell lymphoma

Anti-CENTROMERE,

The limited cutaneous

Produced exclusively by
adipocytes
Enhances insulin
sensitivity, and inhibits
many steps in inflammation
Reduced in Metabolic
Syndrome, hence, causing
the insulin resistance
Bone marrow infiltration of
monoclonal B cells; (for the
null:non-T & non-B)
Smudge cells (basket cells)
w/ immunopositivity to CD30
a.k.a. Ki-1
Clusterin, another marker
that would differentiate from
Hodgkins
Have a golgi-staining pattern

CREST Syndrome (the acronym)

GENETICS | 2
Anti-NUCLEAR Abs, and
Anti-Th RNP

form (lcSSc) of
Systemic Scleroderma

Calcinosis
Raynauds phenomenon
Esophageal dysmotility
(Scleroderma)
Sclerodactyly
Telangiectasia

If lungs are involved: pulmonary


arterial hypertension
Anti-DsDNA
Antibody and AntiSmith antigen

Systemic Lupus
Erythematosus (SLE)

Type III hypersensitivity


reaction
In the HLA region of
Chromosome 6
Malar rash / Butterfly rash
Libman- Sacks endocarditis
mitral insuff.
Accelerated atherosclerosis
Myalgia, hemolytic anemia,
joint pains, fever, fatigue
Class IV: Diffuse Proliferative
Membranous
Glomerulonephritis (with
"wire loop" appearance)
(most severe type)
LE Bodies/ Hematoxylin
bodies
Bibasilar reticular pattern in
the interstitial lung disease of
SLE (shrinking lung
syndrome)
Treatment:
Conservative: NSAIDs,
Hydrochloroquine
For Life-threatening: Systemic
glucocorticoids,
Cyclophosphamide,
Mycophenolate mofetil,
Azathioprine

Anti-GAD Antibodies

Stiff Man Syndrome

These antibodies lead to a decrease


in GABA synthesis ( of inhibitory
neurotransmitters)
Impaired control/regulation of motor
functions muscle stiffness and
spasm
GAD: glutamate decarboxylase
(converts glutamine into GABA)

Anti-GLIADIN
Antibody

Coeliac Sprue

Also ANAb, aENA Ag

Immune-mediated
progressive ataxia
Anti-gliadin IgA: Glutensensitive Idiopathic
Neuropathy
Anti-gliadin IgE: allergy,
asthma
Anti-gliadin IgG: similar to IgA
but higher levels

GENETICS | 3

Tropical Sprue or Enteric


Sprue

Must have a Gluten-free


diet
toxic fraction of wheat,
barley, rye and also of oat

abnormal flattening of the villi


and inflammation of the lining of
the small intestine
Malabsorption will lead to vitamin
deficiency (ADEK, B12)

Anti-GLOMERULAR
BASEMENT MEMBRANE
Antibodies

Goodpasteurs Syndrome
or the
Anti-GBM Disease

Anti-HISTONES Ab

Drug-induced Lupus

Anti-MITOCHONDRIAL
Antibody (AMA)

Primary Biliary Cirrhosis

Anti-NUCLEAR Antibody
(ANA)

Anti-neuronal Ab

CNS lupus

Anti-nicotinic receptor
antibodies

Myasthenia Gravis
Edrophonium (Tensilon)
Test
Repetitive Nerve
Stimulation (JOLLY Test)
decremental response
Single fiber stimulation:
more sensitive than RNS

GBM Antigen in the lungs and


kidneys
Crescents and linear deposits
(staining pattern)
Type II hypersensitivity
HLADR2
Hemoptysis and hematuria

INH, Procainamide, Hydralazine,


Methyldopa, Chlorpromazine,
Minocycline, Disopyramide,
Propafenone, ACE Inhibitors, blockers, Chlorpromazine, Lithium,
Carbamazepine, Phenytoin, PTU,
Sulfasalazine, Lovastatin,
Simvastatin, Macrodantin,
Hydrochlorothiazide, Interferon
inhibitor, TNF inhibitor
MC presentation: PRURITUS
Autoimmune
Has 4 stages:
1. Portal: granulomas
2. Periportal: fibrosis &
inflammation
3. Septal: fibrous septa
4. Cirrhotic: nodules; garland

Decreased binding of Acetylcholine


to nicotinic receptors (problem with
Step#3 of Chemical Transmission)
More common in females
Easy fatigability of the
muscles, weakness at the end
of the day, weakness of the
facial muscles (esp. chewing
meat), weakness of the neck
flexion
Ptosis: the MC clinical
presentation
(NOTE: ptosis is also present in
Horners syndrome: Pancoast tumor)

GENETICS | 4
Thymoma: the MC associated tumor
with MG
DOC: Pyridostigmine
Alt.: Neostigmine

Anti-ribosomal P Ab

Psychosis 2 to CNS
lupus

Anti-Ro Ab

Neonatal Lupus

Anti-SCL-70 Antibody
a.k.a.
Anti-topoisomerase I

Diffuse Systemic
Scleroderma

Congenital heart block

Anti-nuclear antibodies:
Anti-RNA polymerase I,
II, and III
Anti-U3 RNP

Anti-Jo 1

Inflammatory Myopathy

Antiphospholipid Ab

APAS
(anti-phospholipid
antibody syndrome)

Anti-U1 RNP

Mixed Connective Tissue


Disease
overlap syndrome

Overproduced Transforming
Growth Factor
CREST syndrome
GAVE (gastric antral vascular
ectasia) also known as
watermelon stomach
Malignant hypertension
May be caused by
Bleomycin and Taxane

The Anti-U3 RNP is also highly


specific for SSc with
musculoskeletal, gastric and
pulmonary involvement

Scleredema (scleredema
adultorum of Buschke)predominantly in children;
painless edematous
induration involving the face,
scalp, neck, trunk, and
proximal portions of the
extremities

Patients with insulindependent diabetes mellitus


may develop digital sclerosis
and contractures (prayer
hand deformity)

Clotting predisposition
Repeated fetal loss
Thrombocytopenia

In 95-100% of patients
Has features of Sjogrens
syndrome
Has features of Scleroderma
(CREST syndrome)
Has features of SLE: malar
rash, photosensitivity, discoid
lesions, alopecia, painful oral
ulcers
Pulmonary arterial

GENETICS | 5
hypertension is the most
common cause of death
APC Gene
(Adenomatous
Polyposis Coli)

Familial Adenomatous
Polyposis
a.k.a. Gardners
syndrome
(mutations in APC gene)
Colorectal Cancer
(inactivation of APC
gene)
remember 5-FU

APC gene is located in the long (q)


arm of Chromosome 5
[5q21]
Allelic loss: production of an APC
protein that is abnormally short and
nonfunctional
substitution of the amino acid lycine
for isoleucine at position 1307 in
the APC protein
beta-catenin, is controlled by the
APC protein; prevents cell
overgrowth

APOLIPOPROTEIN E4
(APOE4)
Pre-Senilin I
Pre-Senilin II

Alzheimers Disease

ATAXIN-1 Gene

Spinocerebellar ataxia

Neurofibrillary tangles
composed of abnormally
phosphorylated Tau protein
Amyloid proteins; located in
Chromosome 21 senile
plaques
(NOTE: common factor between AD
and Downs syndrome: chromosome
21)
Hippocampal atrophy
(+) Hirano bodies in the
neurons
Average duration: 8-10 years
End stage: Pt will be rigid,
mute, incontinent, bedridden
TACRINE: a medicine for AD
but not used anymore
DOC: AntiAceylcholinesterase Inhibitor
(to prevent further
breakdown of the alreadydepleted levels of Ach)
SCA Type 1: C A G repeat 6p
Hypermetric saccades
Slow saccades
Upper motor neuron
SCA Type 2: C A G repeat 12q
Diminished velocity saccades
Areflexia

Machado Joseph Disease

ATM gene

Inactivated in Ataxia
telangiectasia

SCA Type3: C A G repeat 14q


Gaze evoked nystagmus
Slow saccades
Upper motor neuron
Encodes a kinase essential for p53
activity
Characterized by hypersensitivity to

GENETICS | 6
xrays and predisposition to
lymphomas
Avidin

blocks the co-enzyme


BIOTIN: Vit.B7/Vit.H
(important in the
synthesis of fatty acids
Acetyl CoA)

BACTERIAL PLASMIDs

Found in raw egg whites

Small, circular pieces of selfreplicating DNA that often code for


secondary characteristics such as
antibiotic resistance to the host
cell and toxin production.
Example: exotoxin exfoliatin of
Staph. aureus

BCL-2
(oncogene)

Follicular lymphoma

BCG Gene

Susceptibility to
Mycobacterium disease

centromeric portion of
chromosome 1
regulates directly the process of T
cell-independent macrophage
activation for antimycobacterial
function

BENCE JONES protein

Multiple Myeloma

BJs are monoclonal Ig L chains,


dimeric, either or , but not both
High concentrations are found in
urine
MM is a hematologic malignancy of a
clone of Ig-producing plasma cells
arising in the bone marrow
extremely high levels of
immunoglobulins in plasma;
Abnormal M Proteins (a.k.a. Myeloma
Ig) appear as spike in
electrophoresis

Also seen in:


Waldenstrom
macroglobulinemi
a
Non-Hodgkins
Lymphoma
BOMBESIN
Amino acid peptide

as tumor marker for:


Neuroblastoma
Small Cell CA of Lung
Retinoblastoma
Gastric CA

Punched out lesions: lytic lesions


(Xray)
Mott cells- grape-like clusters
MC primary bone tumor in adults
Bone pain (hallmark)

Stimulates Gastrin release from G


cells
Together with cholecystokinin, it is
the second major source of negative

GENETICS | 7
feedback signals that stop eating
behavior
BRCA1 (17q)
BRCA2 (13q)
(oncogenes)

Ovarian CA
Breast CA

Required for p53 activity

Chargaffs rule

1:1 ratio of Purines and


Pyrimidines

Adenine always pairs with


Thymine/Uracil
Guanine always pairs with Cytosine

CHROMOSOME 4
(Huntingtin gene)

Huntingtons disease

Triple C A G repeat; Autosomal


Dominant
Pathognomonic: atrophy of the
caudate nucleus and putamen
in ACh and GABA
BOX CAR ventricles : on CTScan
(the ventricles become bigger with
the loss/atrophy of the caudate)
Progressive chorea, Pre-senile
dementia, depression, rigidity,
dystonia, MR, seizures, behavioral
problems
The altered huntingtin gene is
believed to interfere with aerobic
respiration must resort to
anaerobic respiration
Glutamate receptors of Px with HD
tend to be oversensitive to
glutamate

CHROMOSOME 5

Cri du Chat
or Lejeunesyndrome

Familial Adenomatous
Polyposis (AFP)
CHROMOSOME 6

Refsums disease

CHROMOSOME 7

Cystic Fibrosis

CHROMOSOME 9

Friedrich Ataxia

Cry of the Cat; cats meow; cats


eyes- epcanthal fold
chromosome 5p deletion
syndrome/5p minus syndrome
deletion on chromosome 5

Peroxin-7 deficiency
CFTR gene; autosomal recessive
(+) Chloride sweat test (>70mmol/L)
MC monogenetic disorder in
Caucasians
Raised transepithelial electric
potential difference: the diagnostic
biological hallmark
Can cause pancreatic insufficiency,
bronchiectasia
FXN gene encodes for the

GENETICS | 8
Ataxia, nystagmus,
kyphoscoliosis, pes cavus
(high arched foot)
Spinal cord becomes
thinner demyelination
Mental functions are not
affected
Treatment: IDEBENONE

protein Frataxin, an iron binding


protein responsible for forming ironsulphur clusters
frataxin deficiency is mitochondrial
iron overload which can cause
damage to many proteins
Expanded G A A triple repeats;
autosomal recessive

CHROMOSOME 10

Refsums disease

Phytanoyl Co-A deficiency


(or Phytannic acid)

CHROMOSOME 13

Patau Syndrome
Trisomy 13
47,XX,+13

Non-disjunction of chromosomes
during meiosis
Micropthalmia, microcephaly and MR
Polydactyly
Cleft lip and palate
Umbilical hernia
Heart and kidney defects
Rocker bottom feet

Retinoblastoma

Leukocoria: Amaurotic Cats


eye/white reflex in funduscopy
Flexner-Wintersteiner rosettes
Mutation in RB1 gene

Long arm: 13q:


Breast cancer
CHROMOSOME 15

Happy Puppet Syndrome


or
Angelman Syndrome
Prader-Willis Syndrome

CHROMOSOME 16

Alpha Thalassemia

BRCA2 oncogene

Maternal C15 is deleted; paternal


sequence is normal
Paternal C15 is deleted; maternal
sequence is normal
Decreased alpha globin production
Hemoglobin H

CHROMOSOME 17

Long arm: 17q:


Von Recklinghausens
Disease

Caf au Lait Spots


Lisch nodules on iris
Neurofibromatosis I

Short arm: 17p13.1:


Li Fraumeni Syndrome

Tp53 Tumor Suppressor Gene


Guardian of the Genome
Several cancers are involved

Long arm:17q:
Ovarian cancer
Canavans disease

Hereditary cancer; germline


mutations of BRCA tumor suppressor
gene
Deficiency of aspartocyclase or
aminocyclase 2 levels of N-acetyl
aspartate are chronically elevated

GENETICS | 9
Progressive demyelination of nerve
cells in the brain death before age
4
CHROMOSOME 18

Edwards Syndrome
Trisomy 18
47,XX,+18

CHROMOSOME 21

Downs Syndrome
Trisomy 21 (47,XY,+21)

Collagen

The most abundant


protein in the body;

Prominent occiput, MR,


micrognathia
Low set ears, short neck
Clenched fist, overlapping
fingers
Heart and renal
malformations
Limited hip abduction
Rocker-bottom feet

Flat facies, oblique palpebral


fissure, epicanthic folds,
simian hand creases
Cong. heart disease
Recurrent infections
Acute lymphoblastic leukemia
(risk)
Premature Alzheimers
disease
Duodenal atresia

VITAMIN C cross links collagen;


scurvy is due to its deficiency

Hydroxylation of Glycine,
Proline into
Hydroxyproline and
Hydroxylysine

Tropocollagen: 3 polypeptide chains

c-JUN gene

Proto-oncogene

Importance:
A growth-promoting gene
Transcription regulation
Negative regulation of DNA binding

C-KIT oncogene

Gastro-intestinal Stromal
Tumors
(GISTs)

C-MYC
(t 8;14)

Burkitts Lymphoma

Tumors are of mesodermal


(interstitial cells of Cajal)
Bleeding or GI obstruction
IMITINAB (Gleevec) as
adjunctive therapy
Epstein Barr virus
starry sky pattern of lymph
node: sheets of medium sized
lymphoid cells
Assoc. with Nasopharyngeal CA

CYP111 and
CYP112

Glucocorticoidremediable
Hyperaldosteronism

There is fusion between these two


genes:
11- hydroxylase and aldosterone

GENETICS | 10
synthase
CYP21A

21-Hydroxylase
deficiency

DNA HELICASE
mutation

Werner syndrome

Mutations in this gene causes


defective conversion of progesterone
to 11-deoxycorticosterone
1. Salt-wasting syndrome:
complete deficiency of 21hydroxylase
2. Simple virilizing adrenogenital
syndrome without salt
wasting
3. Non-classic (late onset)
adrenal virilism: partial 21hydroxylase deficiency
acne, hirsutism, menstrual
irregularities

DYNEIN defect

DYSTROPHIN
(the BIG gene)

Primary Ciliary
Dyskinesia

Duchenne Muscular
Dystrophy

Kartageners syndrome
Triad:
1. Situs invertus (dextrocardia)
2. Chronic sinusitis
3. Bronchiectasis

DYT3 Gene

XDP
Sex-linked Dystonia of
Panay

Erb-B2 (Her2/Neu)
(oncogene)

Breast, Ovarian, Gastric


CA

Excision endonuclease

Xeroderma pigmentosum

Premature aging
accelerated accumulation of
chromosomal damage
mimics the injury that
normally accompanies aging

MC form of childhood
muscular dystrophy
(+) Gowers Sign
Pseudohypertrophy of the calf
Frameshift mutation in 96%
New mutation in 30%

Found in Panay Island Philippines


LUBAG
unique to adult Filipino men
pronounced atrophy of the
caudate and putamen
(just like Huntingtons
disease)

Excision endonuclease is deficient


Autosomal recessive
Extreme sensitivity to sunlight, skin
freckling, ulcerations, skin cancer

Damage: nucleotide excision


repair of Thymine dimers (G1)
is deficient

GENETICS | 11

Familial -Lipoprotein

Tangiers disease

Cause: UV radiation
Repair enzymes: DNA
polymerase, DNA ligase

Absence of HDL(good cholesterol)


receptor protein very low HDL in
the blood
HDL cholesterol < 5 mg/dL in
homozygous individuals
HDL cholesterol between 5
and 30 mg/dL in
heterozygous individuals
Due to a mutation in the gene called
ABCA1
Clouding of cornea (also in
Hurlers syndrome)
Tonsils appear orange/yellow
and enlarged
Neurological abnormalities
(including peripheral
neuropathy, decreased
strength, loss of pain or heat
sensation, muscle pain)
Abdominal pain, diarrhea
Appearance or yellow patches
on the intestinal mucosa,
including the rectum
Enlarged liver
Enlarged spleen
Premature cardiovascular
disease

FIBRILLIN-1

Marfans syndrome
Tall, lanky, long limbs,
long thin fingers
(dolichostenomelia)
With CHD: cystic
medial necrosis,
MVP, aortic
regurgitation
(+) Barlow syndrome
(midsystolic click)
subluxation of the
lens (ectopia
lentis),
Astigmatism,
Nearsightedness

FMR protein

Fragile X syndrome

The gene FBN1 encodes for


the connective tissue protein:
FIBRILLIN-1
there is also excessive Transforming
growth factor (TGF-), which the
fibrillin-1 normally bindsaffects the
vascular smooth ms development
and integrity of the ECMatrix

Familial mental retardation protein


Abundant in brain and testes

fragile site on Xq27.3


Multiple C G G nucleotide
repeats (average #: 29;
range: 6 - 55)
Abnormal gene methylation

GENETICS | 12

FRATAXIN Gene
(a mitochondrial
protein)

Friedreichs Ataxia

GHRELIN

the hunger hormone

Glycogen branching
enzymes

Glycogen Storage
Disease type IV:
Andersens disease

Glycogen debranching
enzymes 1,6

Glycogen Storage
Disease Type III:
Coris Disease
(Forbes disease)

and transcriptional
suppression
Affected males: progressive
neurodegeneration, severe
MR, enlarged testes
Affected female: premature
ovarian failure
expansion of an intronic G A
A triplet repeat;
areflexia, upgoing toes,
vibration and position sense
deficits, scoliosis,
cardiomyopathy, hammer
toes
Idebenone, a free-radical
scavenger, may improve
myocardial hypertrophy in
FA
iron chelators and antioxidant
drugs can increase
myocardial injury in FA

increases the appetite and favors the


accumulation of abdominal fats
produced mainly by P/D1 cells lining
the fundus of the human stomach
and epsilon cells of the pancreas
increased in Metabolic
Syndrome
Amylopectinosis
Polyglucosan body disease
Failure to thrive
Muscle weakness
Hepatomegaly
Hypoglycemia
Hyperlipidemia
Limit dextrinosis

GLUTAMIC ACID
substitution by VALINE
in position 6

Sickle Cell Anemia


(a.k.a. HbSS)
Valine DDx: Maple syrup
urine disease

GRANZYME B

Missense Mutation
Hemolytic crisis - anemia
Sequestration crisis - spleen
Parvovirus B19 triggers
Aplastic crisis
Benefit from routine Flu
vaccine
Sickle shape gives resistance
to Malaria
indigenous inhabitants
of Sub-Saharan Africa
A CTL-derived serine protease

GENETICS | 13
Activates multiple caspases, thereby,
directly inducing the effector phase
of apoptosis
HER-2 oncogene

Breast carcinoma

Histidine

HLA B27

Indicates a poor prognosis if


(+)
Can be treated with targeted
therapy, such as Herceptin

The buffering capacity of hemoglobin


is due to this amino acid residue
Ankylosing Spondylitis
(a.k.a. Marie Strumpell
disease /
Bechterews disease)

MC Seronegative Spondyloarthropathy
bamboo spine appearance
(+) Schober Test: limitation of
lumbar flexion
(+) Sacroilitis on XRay

Reiters Syndrome
Triad:
1. Inflammatory (reactive)
arthritis
2. Conjunctivitis (uveitis)
3. Urethritis (in men) or
Cervicitis (in women)

Behcets syndrome

Keratoderma blenorrhagica
most common triggers are intestinal
infections with Salmonella,
Shigella or Campylobacter and
sexually transmitted infections
with Chlamydia
trachomatis or Neisseria
gonorrheae

HLA B47

21-hydroxylase
Deficiency

HLA DR2

SLE

HLA DR3

Primary Sjogrens
syndrome
Diabetes Mellitus
type 1
SLE
Postgonococcal
arthritis

Oral and genital ulcers


Uveitis (HLA B27)
Progressive optic atrophy
Intracranial hypertension with
papilledema

Sicca syndrome
Schirmers test

GENETICS | 14
HLA DR4
(DR 1*0401)risk
(DR 1*0404)
(DR 1*0101)
Rheumatoid Factor
in 66% of Px
Anti-Cyclic
Citrullinated Peptide
(anti-CCP)
95% specificity
Indicates poor
prognosis

Rheumatoid Arthritis
TNF-: inflammation,
fever, bone and cartilage
resoprtion
IL-1: attacks thymosites
and neutrophils
IL-1: attacks B&T cells,
and tissue cells
IL-6: differentiation and
bone resorption
Rheumatoid nodule
CAD and carotid
atherosclerosis: MC
cause of death in RA px

hMLH1 or hMSH2

HNPCC

HPC1

Prostate Cancer

HUNTINGTIN protein

Huntingtons Disease
(autosomal dominant)

Persistent inflammatory synovitis


MC form of CHRONIC arthritis
Symmetric polyarthritis,
results in joint damage
Systemic disease with
extraarticular mx (>3joints);
s/sx >6weeks
Early morning stiffness >one
hour
SMOKING: most impt environmental
factor related to
Pannus formation: thickened cellular
membrane of granulation reactive to
fibrovascular tissue; with prevailing
fibroblast-like synoviocytes
Hallmarks:
Cartilaginous destruction
(thinning)
Focal bone erosions
Synovial inflammation and
proliferation joint deformity
Clinical features: (skeletal)
Swan neck deformity
Boutonniere deformity
Z Line deformity
Hammer Toe
Mallet toe (resists
straightening)
Claw toe (spares the big toe)
Bakers cyst (knee to
popliteal fossa inflammation)
A mutation in any of these two genes
initiates defective repair of DNA
mismatching, resulting in Hereditary
Non-polyposis Colorectal Cancer
The susceptibility locus for prostate
cancer on chromosome 1 (1 in 500
cases)

JUMPING Gene

Triple C A G repeat
(trinucleotide repeat)
Chorea
Dementia, behavioral
disturbance
Caudate nucleus
Chromosome 4

Transposons;
DNA sequence that can move around
to different positions within the
genomes

GENETICS | 15
K-RAS Gene

Colorectal CA
Pancreatic CA
Lung CA
Noonan syndrome
Cardio-facio-cutaneous
syndrome

LEPTIN

Microphthalmia
associated transcription
factor (MITF) gene

MC site: Sigmoid colon


An oncogene that is a G-PROTEIN
A molecular on/of switch

Inhibits appetite by counteracting


the effects of neuropeptide Y: a
potent feeding stimulant secreted by
the cells in the gut and in the
hypothalamus
Reduced in Metabolic
Syndrome
Tietz syndrome

Mirror images

Deafness
Albinism
Leucism
(defects in all types skin pigments,
not just melanin)
Enantiomers (in biochem)
Reed-Sternberg cells (in patho)

Motif

Helix to helix
Zinc finger
Leucine zipper

Sequence pattern of nucleotides in a


DNA sequence or amino acids in a
protein

NAGA gene

Schindler disease
(a.k.a. Kanzaki disease)

-N-acetylgalactosaminidase
deficiency
I.
Type I (Infantile): more
severe, with neurological and
neuromuscular symptoms
II.
Type II (Adult): milder;
angiokeratomas, mild
intellectual impairment
III.
Type III (Intermediate):
seizures, MR, autistic-like
behavior, delayed speech

NRAM Genetic protein


(Natural Resistance
Associated
Macrophage)
P-16

AIDS

Mycobacterium Avium Intracellulare


("Lady Windermere syndrome")
collarstud abscess

Pancreatic CA

P-53 Tumor Suppressor


Gene

Li-Fraumeni Syndrome
several kinds of
CANCER are involved;
often appears at a young

Very specific for pancreatic


CA
The most frequently
inactivated tumor suppressor
gene

Guardian of the Genome


TP53 assists in repair or
destruction of "bad" or
damaged DNA

GENETICS | 16
age; and, often appears
several times throughout
the life of an affected
person

PHILADELPHIA
Chromosome
(t 9;22)

Chronic Myelogenous
Leukemia

Prevents a cell with damaged


DNA from entering the S
phase
Inactivation or deletion of p53
is associated with Li-Fraumeni
syndrome

Abl (Abelson): a leukemia virus that


carries a similar protein
DOC for CML: Busulfan

Phosphatidyl-inositol
glycan (PIGa)

Paroxysmal Nocturnal
Hemoglobinuria

Hemolytic anemia caused by an


ACQUIRED intrinsic defect in the cell
membrane
Acquired somatic mutations in PIGa

PKD 1 Gene

Autosomal Dominant
Adult-onset Polycystic
Kidney Disease

a Ciliopathy:
PKD may result from mutations of
signaling and environmental sensing
proteins, or failure in intraflagellar
transport, producing the
characteristic multiple cysts

PKD 2 Gene

Autosomal Recessive
Polycystic Kidney
Disease
(presents in childhood)

Associated with:
Berry Aneurysms
MVP, Aortic reg
End Stage Renal Disease
Polycystic Ovaries/Liver

PLA2G6 gene
mutation

Infantile neuroaxonal
dystrophy

Polymerase Chain
Reaction (PCR)

Pribnow Box

No s/sx at birth, but begins at


around 6-18 months
Initial hypotonia, gradually
becomes spastic
Nystagmus, strabismus, optic
nerve atrophy
Hearing loss
Dementia
Low levels of A2 Phopholipase

Enzymatic method for the repeated


copying (and thus AMPLIFICATION) of
the two strands of DNA that make up
a particular gene sequence
a.k.a. Pribnow-Schaller
Box

Sequence TATAAT of six


nucleotides (thymineadenine-thymine) that is an
essential part of a promoter
site on DNA for transcription
to occur in bacteria
Involved in the initial
recognition of the promoter
by RNA polymerase

GENETICS | 17
Ramachandran Plot

Rb 13q
(oncogene)

The angles of the two most common


types of secondary structure, -helix
and sheet, fall within the lower and
upper left-hand quadrants
Retinoblastoma
Osteosarcoma

S-100 protein

As tumor marker for:


Malignant
Melanoma
Malignant
Peripheral Nerve
Sheath tumors
Schwannoma
Histiocytoma
Clear Cell
Sarcoma

S Phase

Flexner-Wintersteiner pseudorosettes
sunburst pattern on Xray

mc: Superficial Spreading type or the


nested pattern
Dysplastic nevus: precursor of
MMelanoma

The phase is the cell cycle when DNA


undergoes replication

Shine-Dalgarno
Sequence

SHOX gene
(short stature
homeobox on
chromosome X)

Short stature in Turner


syndrome

SIRTUINS

SPECTRIN
defect

Ribosomal binding site in the


mRNA generally located
upstream of the start codon/
initiating codon: AUG
Helps recruit the ribosomes to
the mRNA to initiate protein
synthesis by aligning it with
the start codon
Found in prokaryotes
Core DNA sequence:
5TATAAA3
Kozak Sequence: the
eukaryotic equivalent of
Shine Dalgarno sequence

Loss of both copies of the SHOX


45,X: XO Monosomy (absence
of the Barr body)

A family of proteins with histone


deacetylase activity
Increase the production of
proteins that reduce
apoptosis, stimulate protein
folding, increase metabolic
activity and insulin sensitivity
and reduce ROS
Hereditary spherocytosis

red blood cells that are sphereshaped, therefore more prone to

GENETICS | 18
hemolysis
(+) Howell-Jolly bodies
Anemia, hyperbilirubinemia,
splenomegaly
STK11 gene on
Chromosome 19
(mutation)

Peutz-Jeghers syndrome
(a.k.a. hereditary
intestinal polysposis
syndrome)

Tamm Horsfall protein

TATA Box

TAU Protein

Uromodulin
Protein in the kidney tubules
a.k.a. Goldberg-Hogness
Box

Taupathy
Alzheimers disease

Watson and Crick


model of DNA

Benign hamartomatous polyps of the


GIT
Hyperpigmented macules
around the lips and oral
mucosa
Oral findings are same with
Addisons disease and McCune
Albright

34A: one complete turn


or helix pitch of the
Watson and Crick
Helicase: the enzyme
that will unwind the DNA
helix

A DNA sequence (cis regulatory


element) found in the promoter
region of genes in eukaryotes
Hyperphosphorylation will lead to
self-assembly of tangles of paired
helical filaments and straight
filaments
Decribes the DNA as following:
Base pairing
Helical
Right-handed
Complimentary strands
Anti-parallel strands
Sugar-phosphate backbone
outside and bases stacked
inside
Twisted ladder structure

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