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It’s a Head & Neck…
Question: What is a gene?
Answer: A unit of DNA that determines the basic human
form and function.
Question: Define genomics.
Answer: The identification of genes and pathways and
determining how they interact with environmental factors in
health and disease.
Question: What is the ENCODE project?
Answer: Aims to create a comprehensive encyclopedia of
the functional elements encoded in the DNA sequence by
cataloging the identity and precise location of all of the
protein-encoding and non-protein-encoding genes within
the genome.
Question: Draft sequences of the genomes of which two
species are now available?
Answer: Homo sapiens and Mus Musculus.
Question: All genetic information is encoded in the
sequence of _______bases composing molecules of
DNA.
Answer: Four
Question: The human genome contains
approximately_______ genes. These genes encode the
sequence of more than ______distinct proteins.
Answer: 30,000; 100,000
Question: Each somatic cell contains____ chromosomes,
the size and structure of which are the same in every
person.
Answer: 46
Question: True or False: Each chromosome consists of a
single continuous DNA molecule.
Answer: True
Question: True or False: In addition to the nuclear genome,
each mitochondrion contains several copies of a linear
DNA molecule of approximately 16,000 base pairs.
Answer: False
Question: True or False: Mutations in mitochondrial DNA
account for a set of diseases with a distinctive pattern of
sex-linked transmission.
Answer: False
Question: What is a genotype?
Answer: The genetic constitution of a particular genetic
locus.
Question: What are alleles?
Answer: The particular forms of a gene on each
chromosome.
Question: What is the phenotype?
Answer: The observable characteristics of a cell or
organism that are controlled by a particular genetic locus.
Question: Two heterozygous parents have an offspring
with autosomal recessive deafness. What is the
likelihood that the unaffected offspring are carriers?
Answer: 67%
Question: What is the founder effect?
Answer: Many autosomal recessive disorders are more
frequent in specific racial or ethnic populations,
representing the expression of a mutation that was present
in one or a few of the founding members of a group (a
founder effect) and a tendency for marriages to occur
within the same group.
Question: True or False: Autosomal recessive deafness,
is entirely consistent with a normal life span and normal
reproduction.
Answer: True
Question: True or False: If two parents both have
autosomal recessive deafness, it is most likely that their
children will be deaf.
Answer: False: It is more typical for such couples to have
all normal-hearing children because there are many
genetic causes of deafness and most such couples have
different genetic forms of deafness.
Question: For autosomal dominant traits are expressed in
heterozygotes, there is a _____ chance of passing on
the mutant gene to an offspring.
Answer: 50%
Question: Both parents of a child with an autosomal
dominant disorder appear to be unaffected. What can
account for this?
Answer: Rate of penetrance of the disorder
Question: What is the inheritance pattern of NF-1?
Answer: Autosomal dominant
Question: What is the most prevalent symptom in carriers
of NF-1?
Answer: Five or more cafe-au-lait spots by age 20.
Question: 50% of patients with NF1 appear to have no
family history of the disease and probably do represent
new mutations. What accounts for this apparently high rate
of mutation in the NF1 gene?
Answer: The gene is large and perhaps because
segments of the gene sequence are predisposed to
mutation.
Question: True or False: X-linked traits are passed from
male to male.
Answer: False
Question: X-linked Kallmann syndrome is caused by a
mutation that results in a deficiency of hypothalamic
gonadotropin-releasing hormone. The protein product of
the gene KAL appears to act during embryogenesis as a
_____
Answer: Cell-adhesion molecule responsible for normal
neuronal cell migration.
Question: True or False: X-linked dominant traits can be
expressed in both males and females.
Answer: True
Question: Down Syndrome is trisomy 21. Other
chromosomal abnormalities compatible with live births
include trisomies for chromosomes _______ and
________.
Answer: Possible answers:13, 18, X, and Y.
Question: Chromosome loss is less well-tolerated, usually
leading to death in utero The apparent exception is the
______ karyotype, ______syndrome.
Answer: 45, X; Turner Syndrome
Question: What is the mechanism underlying
abnormalities of chromosome number?
Answer: Occur sporadically as a result of errors of
chromosome segregation during meiosis.
Question: Name 2 of the 4 types of chromosomal
rearrangement.
Answer: Deletion, duplication, translocation, inversion
Question: What is a microdeletion syndrome?
Answer: A microdeletion syndrome results from
duplication or deletion of a small segment of chromosome
material that contains a small number of genes, which are
functionally unrelated but by chance are linked together on
the chromosome.
Question:
What is Smith Magenis? Why is it dreaded by head and
neckers? BONUS points if you can give me the exact word that we dread!
Answer:
Smith-Magenis syndrome is caused by a microdeletion in
chromosome 17, is associated with mild to moderate mental retardation; mild
dysmorphic features such as broad feet and hands; peripheral neuropathy;
hearing loss associated with recurrent otitis media; a disturbed pattern
of sleep that can be very disruptive to the family; and specific self-destructive
behaviors, most notably polyembolokoilamania (inserting foreign objects into
bodily orifices, including the ears and nose) and onyehotillomania (pulling out
fingernails and toenails).
Question: What is cloning and how is it useful?
Answer: Segments of human DNA, which may represent
random fragments of the genome or may correspond to
specific expressed genes, can be inserted (cloned) into
bacterial, viral, or yeast DNA and grown in culture.
Question: What is FISH?
Answer: Fluorescence in situ hybridization (FISH):
Absence of the fluorescent signal from the probe indicates
a deletion.
Question: What are the 2 basic ways to clone a gene?
Answer: 1. Knowledge of the structure of the protein
produced by the gene of interest to lead to the gene itself;
2. Positional cloning involves cloning genes for which the
protein products are not known.
Question: What is linkage analysis?
Answer: Linkage analysis uses genetic markers whose
location in the genome is known. The disease gene is
followed through members of families and tracked with
various genetic markers. Segments of DNA that are linked
or located near each other on a chromosome tend to travel
together through a family.
Question: Name 3 inherited disorders caused by
trinucleotide repeat expansion.
Answer: Fragile X syndrome, FRAXE syndrome, Friedrich
ataxia, Huntington disease, Kennedy disease, Myotonic
dystrophy, pinocerebellar ataxia type I .
Question: What are the most commonly repeated
trinucleotide sequences?
Answer: CAG or CGG
Question: True or False: Mutations in mitochondrial genes
are therefore transmitted from a mother to all her male
and female children.
Answer: True.
Question: True or False: Because mitochondria may be
present in sperm, the father can pass a mitochondrial
mutation to any child.
Answer: False
Question: True or False: In fragile X syndrome expansion
is limited to oogenesis, so daughters of unaffected
transmitting males for fragile X syndrome are never
affected.
Answer: True.
Question: In trinucleotide repeat expansion disorders,
describe the phenomenon of genetic anticipation.
Answer: Once a DNA repeat begins to expand in length,
expansion can continue with each succeeding generation.
This dynamism of the trinucleotide repeat sequence
explains a phenomenon known as genetic anticipation,
where the age of onset of the disorder is younger with
each succeeding generation and is accompanied by a
more severe phenotype.
Question: What is genetic imprinting?
Answer: For most genes, both copies are genetically
active. For other genes, however, only the maternally or
the paternally inherited copy is genetically active. Each of
these genes is imprinted during either paternal or maternal
gametogenesis.
Question: Name two disorders due to genetic imprinting
and indicate which one is associated with paternal
/maternal origin?
Answer: Prader-Willi Syndrome; Angelman syndrome.
Question: True or False: Mutations in the noncoding
regions (e.g., promoter region, splice sites, and
termination and polyadenylation signals) of the gene
also can result in abnormal proteins or reduced levels of
normal proteins.
Answer: True
Question: What is PCR?
Answer: Short sequences of single-stranded DNA that are
homologous to sequences on the opposite strands of
genomic DNA serve as the flanking regions for
amplification of a DNA fragment of interest.
Question: True or False? Genes are transcribed from 3’ to
5’.
Answer: False
Question: What are polymorphisms and why do they not
have phenotypic effects?
Answer: Minor variations of base sequence,
polymorphisms, are common in the human population.
Most of these variants are not located in coding regions of
genes and are therefore not responsible for phenotypic
effects.
Question: What is the holy grail of gene therapy?
Answer: The long-term hope for genetic therapy is to
replace a defective copy of a gene in the cell and reverse
the effects of the mutation.
Question: How does Gleevec work?
Answer: Tyrosine kinase inhibitor, imatinib mesylate
(Gleevec) woks by inhibiting the effects of the ABL tyrosine
kinase (CML).
Question: Describe Kartagener’s syndrome and its mode
of inheritance.
Answer: Kartagener’s syndrome is an autosomal
recessively inherited condition of dextrocardia, situs
inversus, immotile sperm, anosmia, bronchiectasis, and
chronic cough, all secondary to absence or malformation
of the dynein arm structures of cilia.
Question: About ____% of congenital HL is genetic.
Answer: 60%.
Question: True or False: Both congenital and acquired
forms of deafness may have a genetic basis.
Answer: True
Question: True or False: Both congenital and acquired
forms of deafness may have a genetic basis.
Answer: True
Question: What is the genetic basis of Usher syndrome?
Answer: Usherin, the protein made by the USH2A gene, is
located in supportive tissue in the inner ear and retina.
Usherin is critical for the proper development and
maintenance of these structures, which may help explain
its role in hearing and vision loss.
Question: What is Pendred Syndrome and what is its
mode of inheritance?
Answer: Autosomal recessively inherited nonsyndromic
deafness and goiter and an increased risk of thyroid
carcinoma.
Question: Describe tissue microarrays.
Answer: Tissue microarrays allow simultaneous analysis
of the expression of thousands of genes and may enable
researchers to identify genetic changes rapidly and
efficiently. Tissue from up to 1,000 histology blocks can be
arrayed onto a newly created paraffin block at designated
locations. Molecular markers can then be applied, with
information assessed for clinical significance.
Question: What is palifermin?
Answer: Palifermin (Kepivance, Amgen), a recombinant
keratinocyte growth factor, was approved by the U.S. Food
and Drug Administration December to decrease the
incidence and duration of severe oral mucositis in patients
with hematologic cancers undergoing high-dose
chemotherapy.
Question: Name the 2 classes of anti-EGFR agents:
Answer: Monoclonal antibodies (MAbs), which are
directed at the extracellular domain of the receptor and
compete for binding with receptor ligands. Tyrosine kinase
inhibitors (TKI), which are small molecule, adenosine
triphosphate–competitive inhibitors that affect catalytic
activity, autophosphorylation, and signal transducer
contact.
Question: What is the mechanism of action of Cetuximab?
Answer: Binds epidermal growth factor receptor (EGFR)
extracellular domain.
Question: What is the mechanism of action of Avastin?
Answer: Targets vascular endothelial growth
factor
Question: What is the mechanism of action of Herceptin?
Answer: Antibody for HER2-neu overexpression
Question: What is the mechanism of action of Gefitinib?
Answer: Causes mutation in EGFR by targeting catalytic
domain
Question: What is the mechanism of action of AEE78?
And what disease is it used for?
Answer: AEE788 is an inhibitor of both EGFR and vascular
endothelial growth factor receptor tyrosine kinases,
anaplastic thyroid cancer.
Question: True or False: Odorant receptor genes
number more than 1,000 in each mammalian species.
Answer: True.
Question: True or False: Aminoglycoside antibiotics can
be ototoxic in patients receiving ordinary therapeutic
doses.
Answer: True.
Question: True or False: Either erythromycin or cipro can
elevate theophylline levels when given to asthmatic
patients taking theophylline.
Answer: True.
Question: True or False: Staph pneumoniae is sometimes
resistant to cefixime (oral third generation cephalosporin).
Answer: True ( sens to 1st and 2nd gen)
Question: True or False: Haemophilus influenzae is
resistant to amoxicillin in 80% of cases.
Answer: False ( 20%)
Question: True or False: Moraxella catarrhalis is generally
sensitive to cefuroxime.
Answer: True (resistant to amoxicillin)
Question: True or False: Pseudomonas aeruginosa is
treatable with gentamicin.
Answer: True ( also: cipro, and ticarcillin-clavulanate)
Question: True or False: Staph aureus is usually treatable
with penicillin or amoxicillin.
Answer: False: (clinda, amox-clavulanate, cephalexin)
Question: MRSA accounts for _____% of S. aureus
strains?
Answer: 10%
Question: True or False: Anaerobic bacteria such a B.
fragilis are treatable with flagyl.
Answer: True ( also clindamycin).
Question: BONUS: What year was DNA discovered and
who discovered it?
Answer: Watson and Crick, 1953.
Question: BONUS: What is the gene responsible for WSI?
Answer: PAX3 gene
Question: BONUS: What is the name for WSIII?
Answer: Klein-Waardenburg syndrome
Question: BONUS: What is the name for WSIV?
Answer: Shah-Waardenburg syndrome