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Bio 139 Oct 25 - Nov 20 2018
Bio 139 Oct 25 - Nov 20 2018
tumor
Diagnosis 2) Radiation therapy - kills cells at S
or M phase
4. Genetic testing Cobalt and Cesium (burn
- Testing for the presence of skin)
specific mutations in onco- or 3) Immunotherapy - stimulation of a
tumor-suppressor Genes person’s immune system to fight
- In 2002: eight (8) ovarian cancer- cancer cells
related SNP alleles 4) Chemotherapy - use of anti-
5. Imaging techniques cancer drugs
- Determine imagine of tumor 5) Angiogenesis control
through: 6) Gene Therapy
- X- rays for mammogram
- MRI (magnetic resonance Ways to lower risk :) /fun facts/
imaging) ● Eat plenty of fiber
- CT scan (computerized ● Do not smoke
tomography) ● Drink alcohol in moderation or not
Refer to HAND OUT at all
6. Detection of Tumor Markers ● Exercise regularly
- Detection of antigens produced ● Do not become overweight
by cancer cells. Examples: ● Limit dietary fat
- PSA - prostate specific ● Limit sun exposure or use
antigen sunscreen
- CA 125 - tumor cell- ● Learn to recognize the warning
surface glycoprotein; signs of cancer
tumor-associated protein
(does not indicate ovarian End of Lecture on Cancer Genetics
cancer all the time)
Coverage of Exam 2
EXAM THREE
Drug addiction
❏ Tolerance
Narcolepsy with cataplexy
The need to take more of
l Drug addiction produces
a drug to achieve the
stable( not transient) changes in
same effect
the brain
❏ Dependence
l Heritability is 04-0.6
The onset of withdrawal
l Twin and adoption studies support
symptoms with cessation
role of genes in drug addiction
of drug
Brain
● Drug addiction produces stable - neurons ~ 100 billion
(not transient) changes in the - neuroglia ~ at least 1 trillion (NS cells
brain that support and provide nourishment to
● Heritability is 0.4-0.6 neurons)
● Twin and adoption studies
support role of genes in drug Drug addiction
addiction - Tolerance
The need to take more of a drug
to achieve the same effect
- dependence
The onset of withdrawal
symptoms with cessation of drug
❏ Serotonin, a neurotransmitter,
can affect mood, emotion,
appetite, sleep, and learning
❏ Many antidepressive drugs are
1) Nicotine binds to the receptor (which serotonin reuptake inhibitors
also binds acetylcholine). (SSRIs) including Prozac, Paxil,
2) This triggers release of dopamine and Zoloft.
from vesicle and into the synapse
Schizophrenia
3) Some dopamine bind receptors on
❏ 1% of the world population
postsynaptic neuron
❏ Onset: 17-27 in males; 20-37 in
4) Some re-enter the presynaptic
females
neuron via dopamine transporter
❏ A mental disorder
5) Uptake of dopamine in postsynaptic
❏ Loss of the ability to organize
neuron triggers the -pleasurable feeling
thoughts and perceptions
associated with smoking
❏ Leading to withdrawal from reality
Mood disorders Progression of disorder:
❏ Difficulty paying attention
❏ Memory and learning skills ❏ Seven candidate genes as of
affected 2007
❏ Psychosis - loss of contact with ❏ Located in chromosome 6 and
reality; paranoia 22; possibly in other chrom.
❏ Delusion - false belief of ❏ Also chromosomal aberrations:
persecution, power etc. deletions & translocations
❏ Hallucinations - false perception
of something not really there ~ Association studies indicate an
visual, auditory, tactile, gustatory, environmental component
olfactory Risk factors for schizophrenia
Maternal malnutrition
Schizophrenia is a multifactorial Infection by Boyna virus
trait: Fetal oxygen deprivation
Inheritance patterns suggest a genetic Obstetric or birth complication
component Psychoactive drug use (PCP)
Traumatic brain injury
Herpes infection at time of birth
Classification of IEMS
1. Disorders of Amino Acid and
Peptide Metabolism
2. Disorders of Carbohydrate
Metabolism
3. Disorders of Fatty Acid and
Ketone Body Metabolism
4. Disorders of Energy Metabolism
(some Mitochondrial)
5. Disorders of Purine/Pyrimidine/
Metabolism
6. Disorders of Sterol Metabolism
7. Disorders of Porphyrin and Heme
Metabolism
8. Disorders of Lipid and Lipoprotein
Metabolism
9. Disorders of Protein Metabolism
THE END & Protein Glycosylation
10. Lysosomal & Peroxisomal
November 15, 2018 Disorders
11. Others: neurotransmitter,
INBORN ERRORS OF METABOLISM Vitamins, Cofactors, Trace
❏ Definition of IEM Elements, Metals, Xenobiotics
❏ Disorders that are caused
by a deficiency of enzyme Definition
catalysis or an enzyme IEMS are defined by:
that facilitates the - Their clinical features
transport of biological - Specific enzyme affected (gene
substances locus)
❏ Coined by Garrod AE in - Their pattern of inheritance
1908
❏ A genetic defect in paty of Xenobiotic- a chem substance not
the metabolic pathways naturally produced or present within an
since birth org.
Epidemiology
● Most are very rare but collectively 3. Phenylketonuria (PKU)
they are very common 4. Glucose-6-phosphate
● Frequencies for each individual dehydrogenase (G6PD)
IEM vary deficiency
- Affected by geographical 5. Galactosemia (GAL) and
and ethnic composition of 6. Maple syrup urine disease
the population (MSUD)
Pathophysiology
● Single gene defects result in
abnormalities in the synthesis or
catabolism of proteins, CHOs, or
fats
- Most due to defect in
enzyme of transport
protein that disrupts
● metabolic pathway
● Dr. Carmencita Padilla ● Toxic accumulation
of
Mortality/Morbidity substrate/intermedi
● IEMs can affect any organ ates
system and usually affect multiple ● Defects in energy
organ systems production/
utilization
● Nearly every metabolic disease
has several forms that vary in
age of onset, clinical severity and - Some porphyrias result in
often, mode of inheritance abdominal pain and liver
damage
Examples
Phenylketonuria
● Mental Retardation
● Neurological problems
● Strange urine odor (musty)
● High urine phenylacetic acid
● Unable to convert phenylalanine ● Most common IEM of faty acid
to tyrosine in the liver oxidation
● Inherited defect in phenylalanine ● Incidence - ~1:10K
hydroxylase ● Lipid metabolism is important
● Incidence- 1:16 - 10K during fasting periods
● If untreated, can cause - Lipid lipolysis -> fats (𝞫-
oxidation) -> energy
Galactosemia - 𝞫-oxidation defective in
MCAD
● Typical signs and symptoms
- Recurrent hypoketotic
hypoglycemia
- Reye’s syndrome-like
illness (vomiting, lethargy,
delirium, coma, and
● Unable to metabolize galactose convulsions)
- Liver dysfunction 𝞫-Thalasemia alleles
- Accumulated medium-
chain acyl CoA esters bind
to carnitine and are
exerted in urine ->
secondary carnitine
deficiency (muscle
weakness, hypotonia)
● Treatment
- Administration of IV
glucose - to correct
hypoglycemia and provide
energy
- Carnitine administration
during crisis treat
deficiency and promote
excretion of excess esters
- Avoid prolonged periods of
fasting and treat signs of
hypoglycemia early
● Attacks become less frequent
during childhood and fasting
tolerance improves with
increasing body mass
● Microbiota: “ecological
community of commensalism
symbiotic and pathogenic
microorganisms”
● Microbiome: collective genomes
of microorganism
Metabilike or phenome.
PLDI cancer
Partly heheritable
Bacteriodacea and Bifidibacteriacaea
xo-speciate with great ape hosts.
- Note: proteins are unstable and
degrade easily
- Recall in newborn screening:
tests on the dried blood spot
(BBS) filter cards must be done
immediately
Detection methods (examples):
- Color reaction
- Spectrophotometry
- HPLC Analysis
- immunotechniques
9
Defective enzymes in maple syrup urine
Nov. 29 disease (MSUD)
IV. Issues and Applications - Accumulation of alpha- keto acids
A. Genetic Screening produced by transamination
Involves history taking, physical - Excreted in urine → smells like
examination, conventional tests: maple syrup or burnt sugar
x-rays, biochemical, cytogenetic ,
molecular tests C. DNA-based detection
1. Direct PCR Analysis of deletions
Health professional team - Differently sized-DNA
- Clinical geneticists bands
- Medical specialists 2. Allele-specific oligonucleotide (probe)
- Genetic counselor hybridization
- Social worker Wt probe + wt DNA = hybridize
Wt probe + mut DNA = not hybridize
B. Biochemical Detection Mut probe + mut DNA = hybridize
Involves measurement r detection of:
1. Enzyme activity e.g. G6PDH ddNTP - will stop since it is very specific
activity
2. Level of metabolites e.g. alpha-
keto acids in MSUD
3. Size or quantity of protein
4. Defective structural protein e.g. in
haemophilia and thalassemia
Samples:
- Blood, urine, amniotic fluid, or
cerebrospinal fluid
D. Gene therapy: Classical Approach-
provide correct genes
E. Genetic Counseling
❏ Communication process between
the health professional and the Genetic counseling also helps the family
patient to:
~regarding a genetic disorder in a) Understand the following
the family b) Choose the appropriate action to
❏ Occurrence take
❏ Possible transmission c) Adjust the psychosocial impact of
❏ Manifestations and severity the genetic condition
FORENSIC GENETICS
Forensic Science is the application of
genetics to human and on human
material for the resolution of legal
conflicts
1 in 1/0.00014 or 1 in 7,143
Combined Matching Probability
1 in 3.996x10^(25)