Exam 1 Flashcards

Question

Aneuploidy

Answer 1

A change in chromosomes from 46 *Most individuals have 46 chromosomes *Most result in pregnancy loss EX: Trisomy 21, Monosomy X or Turner Syndrome

Answer 2

When part of a chromosome breaks off and attaches to another chromosome *Genetic material can be gained or lost *Deletions and duplications can also occur at the chromosome level

Answer 3

Variants passed from parent to child *Present in nearly every cell in the body *Also called germline variants

Answer 4

Variants that occur during a person's lifetime *Not present in every cell *Also called somatic variants *Cannot be passed on *Often due to environmental effect (UV radiation)

Answer 5

Cells with varying genetic makeup in the body - Occurs sometime after fertilization - Could be germline or somatic depending on when/where

Answer 6

One altered copy can cause a disorder Can be inherited or arise from a new variant EX: Huntington disease

Answer 7

Need two altered copies for disease to be caused - Individuals with one altered copy can be carriers or have few symptoms - Typically not seen in every generation EX: Cystic fibrosis, sickle cell anemia

Answer 8

caused by a gene variation on the X chromosome -Females show less effect -Fathers cannot pass X linked traits to son -Those who inherit will show the disorder

Answer 9

For females: need variants on both X chromosomes For males: only need one variant (so seen more in males) *Father cannot pass X-linked traits to sons

Answer 10

Disease associated variant on the Y chromosome -Variants are passed from father to son

Answer 11

Two altered variants of the same gene (alleles) are expressed and make different proteins -Both variant influence the trait EX: ABO blood group

Answer 12

-Gene variant in the mitochondrial DNA - Inherited from the mother

Answer 13

Genetic diseases associated with one gene, or one position on the chromosome (locus) -Tend to run in families and are inherited -Simple and better understood than polygenic diseases

Answer 14

The observable characteristic of a gene variant

Answer 15

Genetic diseases that are impacted by multiple loci (positions on the chromosome)

Answer 16

Progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability --> fatal -Typically onset in adulthood -Autosomal dominant -Caused by variants in HTT gene -Contains repeats of the nucleoside triplet "CAG" -Higher numbers of CAG repeats = more severe disease progression, gain of function phenotypes

Answer 17

Excessive CAG repeats CREATE a protein with an additional, TOXIC function

Answer 18

Excessive CAG repeats REDUCE protein function

Answer 19

-Monogenic -Affects hemoglobin -Alters shape of red blood cells--> distorted RBCs get stuck in blood vessels causing severe pain and anemia -Autosomal RECESSIVE -Caused by variants in the HBB gene -People that are heterozygous are protected from Malaria, frequency of HbS variant is highest where malaria is endemic

Answer 20

-Monogenic disease -Build up of thick mucus causes respiratory/digestive problems and leads to bacterial infection -Symptoms often appear in childhood -Variants of the CFTR gene -Autosomal recessive

Answer 21

Role in protecting neurons from apoptosis (cell death) -Variant of this gene causes neuronal degradation

Answer 22

Variant in the CFTR gene (F508del) deletes three nucleotides but the gene is left in the frame -Protein created is left unstable and is degraded by the proteasome

Answer 23

Characterized by progressive muscle weakness and atrophy -L.E is 22 years -Variants in the DMD gene cause absence of dystrophin protein -Protein is required for muscle tissue protection during contraction -X linked recessive --> Mother passes it on, if she is a carrier male child has 50% of getting it and female child has 50% of being carrier

Answer 24

Exons code for proteins -Introns are removed by splicing

Answer 25

Results in different protein products from the same gene -Variants can affect splicing

Answer 26

Exons and introns have sequences that can recruit proteins which either enhance or inhibit splicing EX: ESE, ISE = Exon/Intron splicing enhancer ESS, ISS = Exon/Intron splicing silencer

Answer 27

Can restore proper pre-mRNA splicing -They basically block unwanted splice sites which allow for the mutation to be stopped

Answer 28

Basically we can introduce a ASO which allows for an alternative splice site to be selected which allows for a shorter but functional dystrophin protein EX: Eteplirsen targets exon 51 which blocks it and allows for alternative splice site (gives shorter but functional protein)

Answer 29

Need multiple therapies -Elexacaftor and Tezacaftor stabilize F508del-CFTR and send it to Golgi to be sent out -Ivacaftor potentiates F508del-CFTR activity

Answer 30

Just need therapy to produce a healthy protein

Answer 31

Conditions/diseases that are caused by variants in multiple genes Modulated by lifestyle and environmental factors -Exercise -Diet -Pollution exposure -Etc. Sometimes called complex or multifactorial disorders EX: Hypertension, heart disease, type 2 diabetes, cancer

Answer 32

-Found in families but inheritance is not as clear -Similarity in family lifestlyes/environment a confounding variable -Difficult to study/treat

Answer 33

-The number of gene variants contributing to disease is generally not known -The number of variants carried by parents that can increase risk is not known -The precise qualitative impact of environmental risks is unknown

Answer 34

-Increased likelihood of developing a disease based on the genotype -Often inherited -Can contribute to developing a disease without having it -Having a variant is not deterministic for a disease phenotype -Variants can have small or large effects -Gene variants can interact and change the disease phenotype (modifier genes) -Risk can be estimated but not strictly calculated -Family history can be used

Answer 35

% of individuals with a given phenotype that express it

Answer 36

Degree to which an individual with a given genotype expresses a phenotype

Answer 37

Variants in BRCA1 and BRCA 2 (DNA repair proteins) -Failure to repair DNA results in mutations that lead to cancer -Inherited variants lead to somatic variants which lead to cancer

Answer 38

-High blood pressure -Uncontrolled high blood pressure can lead to cardiovascular diseases and complications

Answer 39

Primary - No identifiable cause of high blood pressure - Tends to develop gradually over many years - Polygenic Secondary - Caused by an underlying disease - Tends to appear suddenly - Typically causes higher blood pressure than primary - Caused by various conditions also (genetic and environmental factors) factors) - Monogenic

Answer 40

1. Identify genomic variants by comparing the genomes of individuals with and without hypertension 2. Calculate which variants tend to be found more frequently in groups of people with hypertension 3. Use statistics to estimate how the collection of a person's variants affect their risk for hypertension 4. Yields polygenic risk scores 5. All of this can be done without knowing how specific genes influence hypertension

Answer 41

We need a lot of information to determine if SNP will result in negative health conseqeunces

Answer 42

Monogenic diseases -Large effect gene variants -Clearly traced through family pedigrees -The Huntington associated variant was identified by cutting human DNA with a sequence-specific enzyme -The enzyme cut the DNA is a distinct pattern

Answer 43

Motivation: -Compared dizygotic (fraternal) and monozygotic (identical) twins revealed their was a genetic component to heritability of traits -Complex/polygenic diseases could be inherited Goal = associated genes with traits -Individual genes likely only have small effects -Scan for markers across entire genomes -Current approach to understanding polygenic diseases They catalog SNPs and examine them to determine if they more frequently in people with the disease -SNPs aren't necessarily causative of disease

Answer 44

Simple/monogenic: -Severe phenotype -Early onset -Rare -Mendelian inheritance -Cystic fibrosis, osteogenesis imperfecta, etc. -Caue mutations Complex: -Mild phenotype -Late onset -Common -Complex inheritance -Diabetes, asthma, osteoporosis, etc. -Polymorphisms

Answer 45

Chips have SNPs that people already know about, and they are very inexpensive to find out if a person has a SNP associated to disease NGS contains SNPs that are unknown

Answer 46

Need to select: -Appropriate population -Genotyping method -Statistical analysis approach

Answer 47

-Population and sample size -Larger populations enable identification of additional significant loci -Ancestry (if people have similar ancestry or not) -Need diverse ancestry

Answer 48

-Hybridization arrays/chips (becoming outmoded) -Whole exome sequencing (selective sequencing of exons)

Answer 49

Enrich only exons for sequencing Enrichment occurs by base pairing of exons with DNA probes Pitfall? -Misses promoter sequence

Answer 50

Significant loci often contain multiple genes How many genes depends on the resolution of the SNP detection technique If we identify multiple genes within the Loci we don't know which gene causes the disease

Answer 51

-Attempt to determine the relative risk for complex diseases -Considers potentially hundreds of genetic variants that modulate disease risk -Incorporates information from GWAS studies -Can assess risk for individuals or populations -Can identify cohorts for further analysis of gene disease connections -Can include environmental risk or utilize biomarkers

Answer 52

Benefits: -Appropriate assessment of risk could improve preemptive care Cons: -Need to consider diverse ancestries -Other issues: access, insuracne coverage, data sharing

Answer 53

The non-coding genome can alter the amount of RNA or protein produced by a gene (gene expression) ~90% of disease associated SNPs are found in non-coding DNA -Many of these SNPs overlap enhancers and silencers, suggesting alterations in gene expression -Effects on expression haven't been verified and it's expensive to do so

Answer 54

-Promoters initiate gene expression and are acted on by -Enhancers increase expression -Silencers reduce expression -Insulators block the effect of enhancers at adjacent genes

Answer 55

Modification of DNA that affects gene expression -Impacted by environment *DNA modification plays a potential role in disease phenotypes

Answer 56

-One size fits all approach doesn't work for everyone -Using genomics to define or predict disease -Based on individual's DNA sequence Personalized genomics = Precision genomics

Answer 57

-Ideally allows for more accurate treatment and prevention strategies -Emerging field -Use of polygenic risk scores to improve patient outcomes is an example of precision medicine -mRNA vaccines can be reprogrammed to target tumors from specific patients -Engineered mRNAs express neoantigens

Answer 58

How a person's genetic background affects drug response is a subfield of precision medicine

Answer 59

Make a diagnosis Plan treatment Determine treatment efficacy Make a prognosis

Answer 60

Biomarkers are DNA/RNA/protein features that correlate with cancer risk or therapy efficicacy -Knowledge of biomarkers has advanced to the point where they can be used to specify treatment -Target tumors based on two markers: Short DNA repeats and DNA mismatch repair deficiency

Answer 61

New proteins found on the outside of tumor cells due to DNA mutations

Answer 62

Avoid adverse reactions -Drug hypersensitivity Decide dosage -Slow drug metabolism --> buildup and toxicity -Fast drug metabolism ---> Lack of drug effect Overall patient health improvement

Answer 63

Genes with varaints that affect drug pharmacokinetics or pharmacodynamics Pharmacokinetic genes -Normal metabolizers -Poor metabolizers -Intermediate metabolizers -Ultrarapid Metabolizers Pharmacodynamic genes -Positive for high risk alleles -Negative for high risk alleles Large effect -Monogenic -rare -individuals Small effect -Polygenic -Common -Populations

Answer 64

Varying numbers of drug receptors on cells can produce varying responses

Answer 65

Drug entry into target cells can be impacted by genotype

Answer 66

Genotype impacts the rate of drug breakdown, which affects dosing

Answer 67

Large scale deletions or duplications affect drug metabolism

Answer 68

Has no activity or less drug metabolism

Answer 69

Any DNA molecule formed by joining DNA segments from different sources -DNA digestion/ligation -Gel electrophoresis -Hybridization -PCR -Transformation of host cells

Answer 70

Restriction endonucleases cleave DNA at specific internal sequences (digestion) Cutting and pasting DNA: Restriction Enzymes and DNA ligase --> Two DNA pieces with the same unique restriction site on each end can be digested with restriction enzyme then mized and treated with DNA ligase to give joined fragments

Answer 71

-Large DNA fragments -Moderate resolution -Horizontal gel -Standard visualization -Pulsed field --> extremely large fragments

Answer 72

-Small DNA fragments -High resolution (single nucleotide) -Vertical gel -Standard visualization -SDS-PAGE

Answer 73

DNA double helices are denatured to single strands by heat or high pH and then slowly cooled/lower ph so that the DNA double helices are reformed via renaturation Contributing factors: -Strand length (longer = more stable) -pH, salt, temp -sequence -can be DNA/DNA, DNA/RNA, RNA, RNA -Tm = temp at 50% -USe of fluorescent dsDNA binding molecule can "report" proportion of dsDNA

Answer 74

Can be modulated With appropriate stringency and sensitivity, annealing techniques can detect complementrary sequences present at the concentration of one molecule per cell

Answer 75

Allows amplification of any gene via base pairing specificity

Answer 76

Way of ogranizing genes Contain the following elements: 1. Regulatory gene --> codes for a protein that binds DNA and influences transcription of the structural gene(s) 2. Operator --> DNA sequence that binds the regulatory protein 3. Promoter --> DNA sequence that binds RNA polymerase in absence of repressor 4. Structural gene --> codes for nonregulatory protein(s) that have activity in metabolism

Answer 77

Encodes three structural genes and one regulatory gene This operon is a group of genes whose expression is coregulated in response to the presence or absence of lactase as a carbon source The first important enzyme required for using lactose is B-galactosidase which cleaves lactose into galactose and glucose In operons the RBS and start codons are usually much closer to stop codon of the upstream gene

Answer 78

1. Plasmid is cut with 2 different restriction enzymes 2. Gene is amplified by PCR from genomic DNA 3. Primers contain same restriction sites as used to cut plasmid 4. Gene is cut to give sticky ends that are complementary to plasmid 5. Cut gene is ligated to plasmid by DNA ligase 6. Plasmid with cloned gene is added to E. Coli in presence of antibiotic Forms Expression Plasmid

Answer 79

Dictates number of plasmid copies per cell

Exam 1 Flashcards

(103 cards)