142 Cards in this Set
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What color topped vacutainer is used to collect blood for karyotyping?
What is such a tube coated with.
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GREEN
Sodium heparin
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What is the active ingredient in prekaryotyping treatment?
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colchicine
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acrocentric
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centromere near end of chromosome
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metacentric
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centromere near middle of chromosome
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submetacentric
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centromere nearer to one end of chromosome than the other
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karyogram
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picture of chromosomes
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karyotype
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description of chromosome
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euploidy
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cell with a set or sets of 23 chromosomes
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aneuploidy
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chromosome number that is not an exact multiple of n (23 chromosomes)
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triploidy
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double chromosome contribution from one parent
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DIANDRIC triploidy
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extra set of chromosomes is paternal
aka: TYPE I triploidy
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DIGYNIC triploidy
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extra set of chromosomes is maternal
aka: TYPE II triploidy (less common than type I)
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aneuploidy
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cytogenetic abnormalities where all or part of one or more chromosomes is added or deleted
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aneuploidy is the result of ______
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nondisjunction (failure of chromosomes to separate normally during cell division)
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viable autosomal trisomies
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Down syndrome (trisomy 21)
Patau syndrome (trisomy 13)
Edward syndrome (trisomy 18)
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viable sex aneuploidies
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Turner's syndrome (45, X)
Kleinefelter syndrome (47, XXY)
47, XYY
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MONOsomy is ____ tolerated than TRIsomy
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LESS
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Crossing over with PARAcentric inversion
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NOT viable
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Corssing over with PERIcentric inversion
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VIABLE
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Robertsonian translocations
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two acrocentric chromosomes fusing at centromeres with loss of satellites and short arms - lost material (rRNA genes) is redundant
phenotypically normal
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21q21q Transloaction (Robertsonian)
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all surviving progeny will have trisomy 21
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isochromosomes
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mirror image chromosomes
two p arms or two q arms joined at the centromere
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Obligate carrier
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individual who is assumed to be a carrier based on other affective relatives
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Consanguinity
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parents share a common ancestor
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Dosage compensation achieved by ____
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X-inactivation in females
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3 examples of X-lined recessive disorder
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Hemophilia A
Fragile X Syndrome
Duchenne Muscular Dystrophy
Red-green color blindness
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Example of X-linked dominant conditio
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Rett syndrome
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Homoplasmy
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all mitochondrial DNA are the same (either with or without a mutation)
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Heteroplasmy
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proportion of normal and mutated mitchondrial DNA in a cell
(proportion can change as cells divide)
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Clinical expression of mitochondrial inheritance depends on (3 things)
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amount of heteroplasmy
tissue distribution of mutatnt mtDNAs
threshold effect (vulnerability of each tissue ot impaired oxidative metabolism)
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Key pattern for dominant inheritance
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vertical transmission
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key pattery for recessive inheritance
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skipping generations
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key pattern for X-linked recessive inheritance
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bias towards affected males
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key pattern for x-lined dominant inheritance
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bias towards affected females
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key pattern for mitochondrial diseases
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affected mothers with all children affected
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What inheritance pattern rules out X-linked and mitochondrial disorders?
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father-to-son transmission
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What inheritance pattern makes autosomal inheritance LESS LIKELY?
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gender bias
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If males transmit the disease, you can rule out ____
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mitochondrial inheritance
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If an unaffected mother has affected children, or if an affected mother has unaffected children, you can rule out _____
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homoplasmic mitochondrial inheritance
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Penetrance
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probability that an individual with a specific genotype will express a phenotype to any degree
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Complete penetrance
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everyone with a given genotype will express the phenotype to some degree
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reduced penetrance
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not everyone with a particular genotype will express the phenotype
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Example of reduced penetrance
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Hereditary cancer syndrome, e.g.: retinoblastoma
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Causes of variability in phenotypic expression (6)
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(1) reduced penetrance
(2) variable expressivity
(3) pleiotropy
(4) allelic heterogeneity
(5) locus heterogeneity
(6) delayed age of onset
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Variable expressivity
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manifestation of a disease is variable amongst individuals that have the same genotype
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Example of disease displaying variable expressivity
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tuberous sclerosis
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Pleiotropy
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a single gene producing diverse phenotypic effects; a pleiotropic ds gene could have multiple adverse effects in different organ systems/body areas
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Example of pleiotropic genetic diseases
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Marfan's syndrome
Cystic fibrosis
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Allelic heterogeneity
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several different mutations of one gene that all cause the same disease
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Example of disease displaying allelic heterogeneity
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cystic fibrosis
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Locus heterogenity
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mutations at different loci (in different genes) causing the same disease or phenotype
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Example of locus heterogenieity
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hearing loss
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Example of disease displaying delayed age of onset
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Huntington ds
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Variability caused by interactions of genes (4 things)
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(1) incomplete dominance
(2) codominance
(3) epistasis
(4) sex-influenced conditions
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Incomplete dominance
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expression of heterozygote (Aa) is different from and intermediate to both homozygotes (AA, aa)
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2 examples of disease showing incomplete dominance
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achondroplasia
familial hypercholesteremia
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Co-dominance
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different alleles have an equal effect on the phenotype - both are expressed
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Example of co-dominance
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ABO blood groups
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Epistasis
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expression of one gene is prevented or modified by another gene (at a different locus)
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Example of epistasis
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H gene codes for the H antigen on teh surface of RBCs
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Sex-influenced diseases are expressed ...
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in both genders, but with significantly different frequencies
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Example of sex-influenced traits
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male-pattern baldness (not an X-linked trait)
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Sex-limited condition
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expressed exclusively in one gender
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Phenocopies
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an environmental influence mimicking a genetic disorder
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Somatic mosaicism
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mutation occurs AFTER fertilization, affecting a subpopulation of cells
Individual manifests ds if percentage of affected cells is high enough
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Example of somatic mosaicism
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segmental neurofibromatosis
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Germ line mosacisim
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Subpopulation of gametes have mutation that individual does not himself express
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In germ line mosacisim, mutation occurs ___ fertilization in the process of ____, not ____
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AFTER fertilization
in the process of MITOSIS
(not meiosis)
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2 examples of germ line mosaicism
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DMD
osteogenesis imperfecta
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Skewed X inactivation
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one cell line (paternal X chr or maternal X chr) is preferentially inactiviated
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Hereditary hemochromatosis
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increased iron absorption leads to multiple manifestations
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Mechanism for microdeletions
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recombination error leading to duplication and deletion of chromosomes
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Wolf-Hirschhorn syndrome - genetic etiology
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loss of terminal material from shot arm of chromosome 4
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Symptoms of Wolf-Hirschhorn syndrome
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profound mental retardation
seizures
ocular hypertelorism
broad or beaked nose
micrognathia
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Cri-du-chat syndrome - genetic etiology
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5p deletion
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Cri-du-chat syndrome: phenotype
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newborns have weak, high pitched cat cry
micrognathia
microencephaly
hypertelorism
epicanthal folds
low set ears
slow growth
severe developmental delay
mental retardation
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VeloCardial Facial Syndrome (DiGeorge Syndrome) - genetic etiology
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Chromosome 22q11 microdeletion
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VeloCardial Facial Syndrome - embryology
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abnormalities affect 3rd and 4th branchial arches of embryonic development, leading to developmental abnormalities in parathyroid and thymus glands, and heat
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VeloCardial Facial Syndrome - phenotype
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parathyroid hypoplasia - hypocalcemia
thumic aplasia - immune deficiency
conotruncal heart defects
dysmorphic facial features
cleft lip, cleft palate
developmental delay
increased risk for schizophrenia
genital abnormalities
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William's syndrome - genetic etiology
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Chromosome 7q11.23 microdeletion (elastin gene)
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Overarching theme of William's syndrome phenotype
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Connective tissue disorder!
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Symptomes of William's syndrome
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microcephaly and elfin-like facial features
supravalvular aortic stenosis
bladder diverticula
hypercalcemia
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Inheritance pattern for Neurofibromatosis: Type 1 (NF1)
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autosomal dominant inheritance (single gene mutation) with complete penetrance, but pleiotropy and variable expressivity
1/2 all new cases = de novo mutation
no ethnic, geographical, sex, etc. bias
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Diagnostic criteria for NF1
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six or more cafe au lait macules
skinfold freckling
2+ neurofibromas
optic glioma (w/ tunnel vision, HA, etc)
2+ Lisch nodules
osseous lesion
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Pts w/ NF1 have a high risk for ___
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CA - NF1 is an overgrowth syndrome!
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NF2 is due to mutations in what gene (nickname)?
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Merlin gene
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Key phenotypic sign of NF2
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bilatera CN8 vestibular schwannomas (symptoms of tinnitus, hearing loss and balance dysfunction)
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Penetrance of NF2
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100% (complete penetrance), with variable expressivity and sometimes delayed age of onset
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Inheritance pattern for Marfan syndrom
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Autosomal dominant with 100% penetrance
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Marfan syndrome caused by mutation to what gene
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FBN-1 gene (fibrillin)
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Diagnostic criteria for Marfan's
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skeletal manifestations
cardiovascular
optic
dural ectasia
family
(NOT DNA testing)
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Three means of determining relative importance of genes vs. environment in ds etiology
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Twin studies
Concordance rates
Heritability
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If concordance rates are similar, heritability is ____
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LOW
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concardance rates
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how often two individuals share the same trait/conditio
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traits mostly determined by genes will have a heritability close to ___
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1.0
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heritability does NOT tell you anything about
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how many genes could be involved
how much each gene contributes to phenotypes
mode of inheritance
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Genetic anticipation
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aka: Sherman paradox
increased frequency of affective relatives, severity of phenotype or earlier age of onset in successive generations
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Etiology of genetic anticipation phenomenon
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trinucleotide expansion of a CGG repeat triplet sequence normally presents in the promoter of the FraX gene - greater number of repeats, greater chance individual is affected
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Premutation
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expansion of a trinucleotide repeat, not significant enough to cause phenotype
unstable - may expand to full mutation in next generation
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Is expansion usually maternal, paternal or both in FraX syndrome?
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maternal
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threshold CGG repeat number for phenotype manifestation in FraX
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200
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2 classes of trinucleotide repeat disorders
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repeats in noncoding regions of a gene
repeats in exonic region of gene
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2 clinical entities relative to FMR-1 locus
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premature ovarian failure
FraX-associated Tremor/Ataxia Syndrome
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genetic description of Myotonic dystrophy
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CTG expansion in 3' UTR of DMPK gene (codes for a myotonin-protein kinase)
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protein-level problem with DTG expansion in 3' UTR of DMPK gene
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protein levels unaffected
problem apparently with expanded mRNA and its processing
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CTG premutation repeat can ___ after MATERNAL transmission and ____ after PATERNAL transmission
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maternal: expand
paternal: contract
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In Huntington's ds, expansion preimary occurs after ___ inheritance
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paternal
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define polyglutamine diseases
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CAG repeats (CAG = dodon for glutamine)
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polyglutamine causes ____ in the ____
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polyglutamine causes protein aggregation in the nucleus
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CAG repeats in HD are considered __-of-function mutations
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GAIN-of-function
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GENETIC IMPRINTING
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different expression of genetic material, at either the chromosomal or allelic level, depending on whether the geneitc materal is inherited from the male or female parent
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5 disease indicating genetic imprinting
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HD
myotonic dystrophy
Fragile X
autosomal dominant spinocerebellar ataxia
NF1
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hydatidiform mole
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occurs when chromosomes in fertilized egg are mostly or all paternal in origin
trophoblastic proliferation with little to no embyronic development
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Imprinting pattern of an individual is established ____ fertilization and ____ during life
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Imprinting pattern of an individual is esatblished BEFORE fertilization and remains established during life.
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What biochemical phenonemenon is strongly associated with imprinting
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DNA methylation
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2 clinical manifestations of imprinting
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Prader-Willi syndrome
Angelman syndrome
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chromosome involved in Prader-Willi and Angelman syndromes
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Chromosome 15
(q11-q13)
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Symptoms of Prader-Willi
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neonatal hypotonia (similar to Trisomy 21)
poor feeding, FTT to age 2
at age 2, hyperphagia
short stature, small hands/feet, micropenis, hypogonadism
mod to severe microencephaly
obesity
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Symptoms of Angelman syndrome
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usu. normal at birth, then manifest:
progressive microcephaly
severe MR, lack of speech onset
gait ataxia
abnormal EEF, seizures
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Deletions in Chr 15q11 inherited from MOTHER results in ____
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Angelman syndrome
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Uniparental disomy - probable mechanism
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initially trisomic zygote subsequently loses chromosome
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Equation for ALLELE frequencies
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p + q = 1
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Equaltion for GENOTYPE frequencies
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p^2 + 2pq + q^2 = 1
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Hardy-Weinberg Equilibrium Principle
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Allele and phenotype frequencies remain constant in subsequent generations
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4 assumptions of H-W Equil.
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Two allels
random mating
large population
no migration, new mutations, natural selection
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Do H-W practice problems, p. 268
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do them!
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2 types of enzymes required for recombinant DNA technology
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Restriction endonucleases
DNA ligases
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Biological function for restriction enzymes
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bacterial defense mechanisms - cut up foreign DNA
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recombinant DNA
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DNA molecule consisteing of components from different "parent" molecules
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cloning
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making many copies of the recombinant DNA using a host organism
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vector
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DNA molecule that can be replicated (i.e.: has an ORI specific to a particular host organism - bac, yeast, etc.)
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Insert
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DNA fragment from organism/individual of interest, which will be joined to a vector
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host
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organism that will replicate the recombinant DNA
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transformation
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process by which teh recombinant DNA is put into the host
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2 essential features of vectors
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insertion site
origin of replication
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plasmid vectors
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small, circular DNA vectors
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cDNA
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capture just one protein coding region per ONE fragment (one insert) for cloning
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how to make cDNA
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synthesize from mRNAs using reverse transcriptases
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what will cDNA not have?
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introns
promoters
enhancers
spacer DNA
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expression clones
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special case of cDNA inserts
get host cell to synthesize protein encoded by cDNA
require expression vectors
use bacterial RNA polymerase and bacteral ribosome to make eukaryotic protein
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clone libraries
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collection of clones, made simultaneously, from a given sample
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How do you differentiate between autosomal dominant and x-linked dominant?
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Can males lead to affected males?
AD = Yes
XD = No
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BMB 462: EXAM 1