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