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60 Cards in this Set
- Front
- Back
Achondroplasia phenotypes are primarily genetically determined. T/F
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T
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–Mental retardation in persons with PKU (phenylketonuria) phenotypes depend on ____ and ____ factors
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Genetics and environmental
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lead poisoning is resulted primarily from ____ factors
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Environmental
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What are the four types of genetic disorders?
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1.Chromosomes and chromosome abnormalities
2.Single gene disorders 3.Polygenic Disorders 4.Mitochondrial disorders |
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In chromosomal disorders, typically there is more than one ___ involved
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One
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Trisomy 21 aka Down syndrome is an example of what kind of disorder?
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Chromosomal
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Single gene disorders are transmitted in a ____ fashion
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Mendelian
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How are these diseases inherited?
•Osteogenesis imperfecta - •Sickle cell anemia - •Hemophilia - |
•Osteogenesis imperfecta - autosomal dominant
•Sickle cell anemia - autosomal recessive •Hemophilia - X-linked |
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Mutated genes of osteogenesis imperfecta
Hemophilia A? Sickle cell? |
type I collagen genes COL1A1 and COL1A2
Factor VIII gene B gloving gene |
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Polygenic diseases
•The most _______ yet still the _______ understood of human genetic diseases •Result from an interaction of ______ genes, each with a_______effect •The ________ alleles are common |
Common, least
Multiple, minor Susceptibility - A gene mutation that increases an individual's susceptibility or predisposition to a certain disease or disorder |
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Type I and type II diabetes, autism, osteoarthritis are examples of what kind of disease?
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Polygenic
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What is a polymorphic marker
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A polymorphic marker is a DNA sequence on a chromosome that is used in the identification of cells, individuals or species. It can also be described as the variations arise, due to mutation or alteration in the genomic loci that are observable.
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A polymorphic marker
A marker that is frequently _____ in the population One can therefore distinguish the two copies of a gene that an individual inherits They are not themselves _______ they simply mark ______ points in the genome |
Heterozygous
Pathogenic , specific |
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What are the polymorphic markers used in mapping studies
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Microsatellites
Snps Variable number tandem repeats (VNTRs) |
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What is a vntr?
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Changes in numbers of repeated DNA sequences arranged in tandem arrays
location in a genome where a short nucleotide sequence is organized as a tandem repeat. These can be found on many chromosomes, and often show variations in length between individuals. Each variant acts as an inherited allele, allowing them to be used for personal or parental identification |
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Micro satellites are a specific type of vntrs that are ___-___ bps in length
They are known as _____ or ______ The most widely used micro satellites are what? |
1-6
Short tandem repeats STR Simple sequence repeats SSR CAn microsatellites |
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SNPs
A polymorphism due to a base _______ or the ---- or ---- of a single base |
Substitution, insertion, deletion
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After finding the marker, the next step is to define the ...
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maximal region
of linkage |
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And then?
Hint: ensemble.org |
Make a list of the genes within the interval
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And thennnn?
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Find the mutation
Target candidate genes within the interval or Target all genes by DNA sequencing |
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Two important considerations for single-gene disorders
______ heterogeneity and ______ heterogeneity |
Allelic and locus
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•Allelic heterogeneity
–The existence of many different disease-causing ______ at a locus •Locus heterogeneity –Determination of the same disease or phenotype by mutations at different ____ |
Alleles,
Loci |
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Polygenic diseases are common or rare?
Unrelated affected individuals share ________ risk alleles |
Ancestral
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A polygenic pedigree has no clear ________ pattern
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Inheritance
Can have effected individual with no effected parents Effected person joining family emphasizes the common nature of the disease |
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Summary
•Mapping single gene disorders –Use clues –If none, use... •A large pedigree •Several smaller pedigrees - but beware of _____heterogeneity –DNA sequence analysis of linked region |
genome-wide linkage analysis, locus
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•Mapping polygenic disorders
–Model-free genome-wide linkage analysis •Now being superseded by genome-wide a-------- analysis –Functional analysis of associated polymorphisms within the refined genomic interval |
Association
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Dr. Alois Alzheimer used staining and discovered what in his patients bwain?
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Plaques and neurofibrillary tangles
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What is the most common cause of dementia. What%?
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Alzheimer's, 70
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Two areas of extreme shrinkage of the brain in Alzheimer's disease
What's enlarges? |
Hippocampus, cerebral cortex
Enlarged ventricles |
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Neurofibrillary tangles
The microtubule-associated protein ____ gets ____________ in Alzheimer’s disease leading to intracellular neurofibrillary tangles, a histological hallmark of the disease. |
Tau, hyperphosphorylated
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Hyperphosphorylation results in the self-_______ of tangles of paired ______ filaments and ______ filaments, which are involved in the pathogenesis of Alzheimer's disease.
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Assembly, helical, straight
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When misfolded, the otherwise very _______ tau protein can form extremely insoluble aggregates that contribute to Alzheimer’s disease and a number of other neurodegenerative diseases called ________.
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Soluble, tauopathies
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Genetics of Alzheimer's disease
Late onset Alzheimer’s Disease - ---% of AD cases - Occurs beyond the age of ___ - Only ___ genetically inherited The ----- allele of the apolipoprotein E gene is linked with the disease. But only ---% of the individuals ---------- for this allele develop the disease. Early onset Alzeimer’s Disease - Less than --% of AD cases - Occurs before the age of 65 - Most cases are -------- cases FAD is inherited in an autosomal _____ way |
90, 65, partly, ApoE4, 30%, homozygous
Familial Alzheimer's disease (FAD) , dominant |
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FAD is caused by a mutation in at least one of the 3 genes..
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- Amyloid Precursor Protein (APP)
- Presenilin-1 (PS1) - Presenilin-2 (PS2) |
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App, ps1, and ps2 is located on what chromosomes?
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21, 14, 1
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Age of onset for app?
Ps1? Ps2? |
50s
20-50 40-50 |
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App is what kind of protein?
What two secretaries cut app? What forms as a result? What is Responsible for the production of amyloid plaques ? -Plaques build up in spaces between ----- cells |
Integral membrane
Beta and gamma secretase: beta secretase is BACEand gamma secretase is ps1/ps2 Result is toxic AB(beta) oligomer, these are responsible for amyloid plaques Nerve |
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High amounts of Aβ forms plaques in between nerve cells and causes cell death
Cell death occurs due to ------ dysfunction and can cause vulnerable neurons to excitotoxicity and apoptosis by a mechanism involving disruption of cellular _____ homeostasis Dysfunctional _____ signaling plays a pivotal role in Alzheimer’s Disease |
Synaptic, calcium, calcium
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Presenilin 1 and 2 are both ------- proteins.
Mutations in either can cause ---- onset FAD cases There are more/less mutations in ps1 than ps2. 185 vs 13 |
Transmembrane
Early More |
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Mutations in PS1 and PS2 are associated with increased production of Aβ___
Aβ___ is the amyloidogenic form of Aβ that is deposited selectively and ---- in Alzheimer’s disease. Ab42 is required for amyloid deposition in transgenic mice |
42, 42, early
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. |
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What is the second most common neurodegenerative disorder?
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Parkinson's
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Parkinson's :
•Causes for disease are both ----and ---- •Disorder of the central nervous system that results from the loss of cells in various parts of the brain, including the ------ -----. |
Environmental , genetic
Substantia nigra |
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oThe substantia nigra produces ---------, a chemical
messenger responsible for signaling within the brain that allow for coordination of -----. oLoss of dopamine causes neurons to fire without normal control, leaving patients less able to direct or control their -------. |
Dopamine, movement, movement
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Pd occurs after the age of
• Symptoms slowness of movement, rest tremor, rigidity, anxiety, depression, disturbance in balance, autonomic disturbance |
50
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What is the pathological hallmark of Parkinson's
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Lewy body or cytoplasmic inclusion body
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Up to how many genes are linked to pd?
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18
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the major protein of the Lewy bodies in PD brain?
Several PD-linked genes play a role in the maintenance of _________ function. |
SNCA=alpha-synuclein
Mitochondrial |
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Longevity can be heritable?
Age for exceptional longevity? What is the basis? -reduced incidence of --- and heart ---- -slowed process of ---- in general |
Yes
90+ Cancer, heart disease, aging |
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Chances to live 100+ year is -- to -- times higher for siblings of centenarians
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8 to 17 times higher
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Change in number centenarians in the Netherlands were mostly men or women?
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Women
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Marital status of male and female Dutch centenarians
Men who were or were not married lived longer? Women who were or were not married lived longer? |
Men who were married lived longer
Women who were not married lived longer |
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Longevity seems to be only ----- heritable.
The nature of genetic influences on longevity is probably -------- (ie. Single genes), suggested by both --------- partitioning of heritability as well as the class of ----- -------. As if Exceptional longevity were like a discrete trait. |
Moderately, non additive, statistical, exceptional longevity
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What protein is associated with longevity?
What are the alleles? |
Cetp - cholesterol ester transfer protein
V and v |
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___ higher % of larger lipoproteins (favorable)
____ lower % of larger lipoproteins (unfavorable) |
VV , vv
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VV 25% in patients 100 years or greater
vv 8 % in patients 70-73 years old __ genotype significantly enriched in those exhibiting the exceptional longevity phenotype. |
VV
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Some genes linked with EL
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LMNA
WRN TEK GIP APOE CDKN2A/B |
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EL may be the result of thousands of -----, each with a ____ effect.
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Variants, small
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What is the most significant and replicated gene in EL?
Despit all of this, what does it explain little of? |
APOE
Genetic Variability |
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EL is determined by a combo of ______ and _____ alleles.
At extreme ages, correlate to very ____ combinations of genetic variants. The picture emerging from this analysis is the EL is the result of an enrichment of longevity associated variants that______ the effect of disease risk alleles and contribute to the ------ of morbidity(onset) and/or disability towards the end of very long lives |
Common, rare
Rare Counter, compression |
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Park1 mutations give rise to mutations in what protein?
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Alpha-synuclein (SNCA)
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