Unit 4 Flashcards
The Genetic Information Nondiscrimination Act of 2008 includes which of the following protections?
An individual can not be denied health insurance on the basis of a genetic test
Under the Genetic Information Non-Discrimination Act of 2008…
a person cannot be denied health insurance because they have a genetic variation that is associated with a small increased risk for breast cancer
True or False: Genetic tests are powerful, but still too expensive to use to improve standard medical care of most people in the US
False
Which of the following DNA sequences in the genome could be referred to as “non-coding” DNA? (Regulatory elements, introns, exons, the long sequences of DNA nucleotides in between adjacent genes on a chromosome)
Regulatory elements, introns, and the long sequences of DNA nucleotides in between adjacent genes on a chromosome
What are introns?
The intervening stretches of DNA that are removed during mRNA processing, so they do not code for amino acids in proteins
Where are regulatory elements?
Upstream from the nucleotides in DNA that code for mRNA
True or False: Genetic variations always change the coding sequence of a protein?
False, genetic variations usually occur in non-coding regions of genes since these regions make up over 99% of the genome
True or False: A coding sequence is the part of a gene that determines if that gene is expressed in a certain cell type or tissue of the body?
False, non-coding regions near the beginning of the gene contain regulatory regions that control which tissues in the body express a specific gene
Which explains why some SNPs don’t result in any changes to the protein produced by a cell?
Many mutations occur in non-coding regions outside of the gene, many DNA mutations are corrected by repair enzymes, and some proteins can have no effect on proteins
What is an example of an SNP?
Replacement of a G=C base pair with an A=T base pair
What best describes the relationship between a gene and DNA?
A gene is a small part of a longer DNA molecule
What kind of DNA variation would you not expect to find in the human population?
Deletion of an entire chromosome
If a disease is caused by a dominant allele, it means that a person with the disease…
could be either homozygous or heterozygous for the allele
A human X-linked gene is…
found on the X chromosome
A woman who carries one recessive X-linked allele will pass the recessive allele on to…
Half of her children
Why do X-linked conditions appear more frequently in males than in females?
A male with a non functioning allele on X does not have another allele of that gene
A human X-linked gene is…..
Found on the X chromosome
What’s required for a trait that is “autosomal recessive” to be expressed phenotypically?
Two copies of the recessive allele must be inherited
An allele is dominant if….
The allele always determines the phenotype
A man who is a carrier for an autosomal allele will pass this allele on to….
Half of all his children
Both of your parents have cleft chins but you don’t. What happened? Why do you look different from your parents? In this case, cleft chin (T) is dominant; no cleft chin is recessive (t).
Both of your parents are heterozygotes (Tt and Tt)
If “cleft chin” is dominant and “no cleft chin” is recessive, what genotype is required to have “no cleft chin”? T=dominant; t=recessive
tt
About one in 400 people in the population carry mutated BRCA1 or BRCA2 genes, and more than half of women with the BRCA1 mutation will develop breast cancer before age 70. BRCA1 is found on chromosome 17, and BRCA2 is found on chromosome 13. The gametes produced by a father who is a carrier for the BRCA1 mutation will:
Carry the BRCA-1 mutation half the time
An autosomal recessive trait….
Will appear only in children of parents who both carry the gene
Two deaf individuals fall in love. Both are from Deaf families: Tim is deaf; Alesha is hearing. Both know their genetic family history–their families share the same gene for deafness. The gene is dominant. However, they don’t know their specific genotypes. If B=Deaf and b=hearing, which is true?
Alesha’s genotype is bb
Sickle-cell anemia is a common disorder that is inherited in an autosomal recessive pattern. A man and a woman who did not have Sickle-cell anemia have one healthy child and one child with Sickle-cell anemia. What is the chance that their healthy child will be a carrier of the recessive Sickle-cell anemia allele?
67% or 2/3
Red-green color blindness is an X-linked recessive trait. What is the probability that a color-blind woman and a man with color vision will have a color-blind daughter?
0%
The polymerase chain reaction (PCR) allows scientists to do all of the following EXCEPT:
Sequence the bases within a gene as it is being copied
Two DNA fragments are separated by electrophoresis in an agarose gel. How is the one that has travelled farther in the gel different from the other?
It is smaller
What DNA sequence would stick to Spot 2 with DNA strands with the sequence ATTCAG?
TAAGTC
True or false?: SNP-chip involves generating sequences of billions of short DNA fragments that are fed into software to reconstruct the sequence of the entire human genome.
False, this is not how SNP-chips work
Which genetic test would be the cheapest and yet still effective test for the variation found in fragile X? Fragile X is caused by mutations in the FMR1 gene , usually caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is inserted in large numbers within the FMR1 gene.
PCR followed by gel electrophoresis is the least expensive option to determine a size difference between two mutations
If an individual only has DNA that binds to the spot containing DNA strands matching the normal allele for the HAXA gene, you can conclude that the individual tested is…
Homozygous for the normal version of the HEXA gene
If a deletion in the PTEN gene is linked to cancer, what type of PCR product would most likely have increased risk of developing cancer?
A smaller PCR product, which would migrate further in gel
Hemophilia A is caused by one of several genetic variations in the F8 gene, which codes for a protein called Factor VIII. The Factor VIII protein helps blood cells stick together to stop the flow of blood at the site of an injury. Known disease-causing variations include SNPs, insertions, and deletions. Which types of tests should be used to test for Hemophilia?
Conventional/single-gene sequencing
What is true about the most common genetic diseases?
They are complex traits that result from interaction of many genes with the environment
True or False: Pharmacogenomics can be used to determine if a patient can have a dangerous reaction to a medication?
True
Which type of inheritance is most likely to cause a bell curve of phenotypes?
Polygenic inheritance
An allele of a gene exists that increases risk for Schizophrenia by 25% or 1.25 times when this allele is inherited as a single copy. Approximately 1% of the US population exhibit symptoms of schizophrenia. Which of the options below would best represent the likelihood that an individual with this allele will develop schizophrenia?
1.25%
What is true about Genome Wide Association Studies?
They look at hundreds or thousands of SNPs at the same time in a large group of people and have been used to identify SNPs associated with complex conditions and response to drugs
Common medical problems such as heart disease, diabetes, and obesity do not have a single genetic cause. They are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Conditions caused by many contributing factors are called…
Complex or multifactorial disorders
Complex or multifactorial traits are influenced by…
Environmental factors such as lifestyle choices
True or false: Pharmacogenomics describes the method of performing genetic tests of embryos during in vitro fertilization procedures.
False
What do Genome Wide Association Studies do?
Use SNP-ChIP or Whole-genome sequencing to test for genetic variations to determine how certain genetic variations make small contributions to a disease
What is the definition of genetic test?
Analysis of DNA to look for a genetic variation that may be associated with a specific trait, such as a disease or disorder
What is the purpose of genetic testing?
It can identify risks for many genetic diseases and results can lead to “pre-symptomatic” treatment decisions
What is genetic discrimination?
Occurs if people are treated unfairly because of differences in their DNA that increases their chances of getting a certain disease
What is an example of genetic discrimination?
A health insurer might refuse to give coverage to a woman who has a DNA difference that raises her odds of getting breast cancer, or employers could use the info to decide whether to hire or fire workers
What is included in the Genetic Information Nondiscrimination Act of 2008?
The law protects people from discrimination by health insurers and employers on the basis of DNA information
What is not included in the Genetic Information Nondiscrimination Act of 2008?
The law does not cover companies with fewer than 15 employees and does not cover life, disability, and long term care insurance
What is hypertrophic cardiomyopathy?
Genetic condition that results in thickening of the heart wall, making it more difficult for blood to leave the heart. Affects 0.1-0.2% of the world population and results in sudden death in ~1% of those with the condition
How is genetic testing related to hypertrophic cardiomyopathy?
Genetic tests now exist for this condition. Olympic policy in Italy requires all athletes must be tested and can excluded from competition on basis of results. Controversy on whether athletes should be tested surrounds this subject
What are the implications of new genetic testing capabilities?
Laws governing genetic testing are incomplete and our votes will be important as we move toward this new future
What is genetic variation?
Any DNA sequence that is different between two people (or two related species)
How do genetic variations lead to differences in genetic traits?
Genetic variations that change protein structure (i.e. the amino acid sequence of the protein) or gene expression can change observable traits
What can DNA changes impact?
By affecting protein structure or gene expression, they can change observable traits
What are proteins?
The molecular machines that do most of the work in our cells
What determines how a protein functions?
The amino acid sequence coded in its genome
What determines where a protein functions?
Gene expression
What are the 3 major types of proteins?
Enzymes, regulators, and structural proteins
What do enzyme proteins do?
Break down or build molecules
What do regulator proteins do?
Control different cellular processes
What do structural proteins do?
Serve as the architectural components of cells and tissues
What is our genome?
All of our DNA (for humans, this is 46 molecules called chromosome)
What is the structure of our chromosomes?
Humans have 23 chromosomes, found in pairs. Everyone has 22 autosome pairs, and 1 pair of sex chromosomes (the X and Y chromosomes)
What is a chromosome?
A long DNA molecule containing thousands of genes
What is a gene?
A short section of a chromosome that codes for a specific protein
What is the anatomy of a chromosome?
They’re made up of coding and non-coding DNA sequences
What are the two types of non-coding DNA sequences?
Non-coding DNA with no function and gene regulatory sequences
What are gene regulatory sequences?
Promotors and enhancers that interact with activators or repressors to control gene expression
What is a gene coding sequence?
The part of the chromosome that is copied into mRNA (transcription) and translated into protein
How many genes are in our genome?
Approximately 25,000-28,000 genes (2 copies each)
If we all have the same chromosomes, with the same genes, in the same order, what exactly makes us different?
Not much; the DNA sequences of any two people are 99.9% identical
How is this different than epigenetic regulation?
Mutations in the regulatory region of the DNA (the promoter DNA sequence or the enhancer DNA sequence) can change how a gene is expressed
What can these changes in DNA sequence cause a gene to do?
Be shut off or turned on, make more or less transcript, express in a tissue it shouldn’t, or not express in a tissue where it should be expressed
What are the three major types of genetic variations?
Single-nucleotide polymorphisms (SNPs), insertions, and deletions
What are SNPs?
Differences in one nucleotide at a specific location on a chromosome
What are insertions?
Insertion of extra DNA nucleotides at a specific location on a chromosome
What are deletions?
Deletion of extra DNA nucleotides at a specific location on a chromosome
How do you determine if a genetic variation might impact a protein structure or gene expression?
Think about where the genetic variation happens on the chromosome
What can genetic variations do?
Change protein structure by altering the amino acid sequence, alter the amount of protein produced or where it is made in the body, or do nothing
What is the structure of chromosomes?
Our cells contain chromosome pairs with 1 copy of each chromosome from each parents so we have 2 copies of each gene on our autosomes
What are alleles?
Different copies of the same gene
What is the genotype?
Refers to the combination of alleles present in an individual’s genome
What is the phenotype?
Refers to the observable traits exhibited by an individual
How is the phenotype determined?
By the interaction of both alleles and by how these alleles interact with the environment
What determines the pattern of inheritance?
The number of variant alleles needed to produce an observable trait
What are single-gene traits?
Autosomal recessive, autosomal dominant, and sex-linked recessive
What are complex or multifactorial traits?
Many genes have small effects on the trait
What is autosomal?
Gene responsible is on an autosome (chromosomes 1-22)
What is recessive?
Both of the alleles of the causative gene must code for an altered protein to show the trait
What is X-linked?
Trait caused by an allele of a gene on the X chromosome?
What does recessive mean in X-linked traits?
Two copies of the recessive allele are needed to show the trait in women
Why do males only need one copy of the recessive allele for X-linked recessive traits?
Since males only have one X, they show the trait if they inherit the allele on the 1 X chromosome they have
How can family pedigrees be used?
Patterns of inheritance can be determined by tracking the inheritance of a trait on them
What to look for on family pedigrees for autosomal recessive?
If a child has a trait, but the parents do not, it must be recessive. You never see two parents with the trait having children without the trait. Recessive traits often skip a generation. If a child has the trait, they had to inherit a copy of the recessive allele from both parents
What to look for on family pedigrees for autosomal dominant?
Often shows up every generation. If a child has the trait, at least one parent will have the trait. Two affected individuals can have unaffected offspring
What to look for on family pedigrees for X-linked recessive?
X-linked recessive traits are observed more frequently in men. Mothers are often carriers because they have two X chromosomes. Traits would only appear in women if their father displayed the trait and their mother was a carrier
How are genetic tests performed?
DNA for genetic testing is obtained from a small sample of blood cells or from cheek cells isolated by swabbing the inside of the cheek
What is the first step of any genetic test?
To make more copies of the DNA
What is PCR?
Stands for polymerase chain reaction. A method of making more DNA copies from a small amount of starting material, can be used to amplify (i.e. make copies of) a short part of a chromosome
How can tests for genetic variations be performed?
One-at-a-time or millions-at-a-time
What are the ways to genetic test one-at-a-time?
PCR followed by gel electrophoresis or PCR followed by conventional DNA sequencing
What are the ways to genetic test millions-at-a-time?
PCR followed by SNP-chip or whole-genome sequencing
What can gel electrophoresis testing determine?
The size of PCR products, which can detect insertions or deletions
What can conventional DNA sequencing determine?
The specific sequence of nucleotides found in a DNA fragment that is ~1000 base pairs long, which can determine SNPs, insertions, and deletions
What is the output of conventional DNA sequencing?
A text file with the specific order of DNA base pairs in the chromosome region that was analyzed
What is the drawback of one-at-a-time genetic testing?
Slow and labor-intensive
How does SNP-chip work?
A microarray, or “chip”, with lots of microscopic spots, each spot containing a short piece of single-stranded DNA that matches one genetic variation is used. Short pieces of DNA from person seeking test are amplified and fluorescent tags are attached to each piece. DNA pieces are heated to make single stranded and added to the chip. DNA hybridizes (sticks by base pairing) only if there is an exact match
Why are SNP-chips useful?
One can do the equivalent of 1 million genetic tests all at once (takes about 16 hours)
What are the drawbacks of SNP-chip testing for genetic variations?
Can only test for SNPs, can only test for a subset of variations at a time, and can only test for variations we already know about
How does whole genome sequencing work?
Chromosomes are fragmented and small pieces of DNA are amplified using PCR. The nucleotide sequence of these short DNA fragments is determined, and software is used to align partially matching sequences to reconstruct the entire genome
How do scientists identify gene alleles (DNA variations) that make small contributions to multifactorial traits
Genome-Wide Association Studies (GWAS)
What are Genome-Wide Association Studies (GWAS)?
A genetic testing study that can identify DNA variations that make small contributions to specific multifactorial phenotypes
How are Genome-Wide Association Studies (GWAS) performed?
By utilizing new genetic testing technologies such as SNP-chip or whole-genome sequencing to examine many DNA variations all at once in many people from two experimental groups (disease vs no disease), scientists can look for variations that are over-represented in one of the groups
What do Genome-Wide Association Studies (GWAS) allow researchers to identify?
Alleles/DNA variations that are correlated with a trail of interest and alleles that are correlated with a complex or multifactorial trait
What p-value means statistically significant?
Usually a p-value < 0.05
What is base risk?
The average risk for a disease or trait in the general population?
What is the formula for risk analysis for complex traits?
Actual risk = Base risk + increase in risk (base risk x % increase in risk)
Example of risk analysis: 40% increase, 5% base risk, what is actual risk?
5% + (5% x 0.4) = 5% +2 = 7%
What is pharmacogenomics?
A powerful new application of genetic test results, it involves evaluating the effectiveness and safety of drugs on the basis of information from an individual’s genome
What can your genome determine using pharmacogenomics?
How well a drug might or might not work for treating a medical condition, and can even influence if you are likely to have an adverse reaction to a drug
True or False: Sequence variations in non-coding sequences can change the mRNA and therefore the protein encoded by the gene.
False, Variations in non-coding sequences can change whether or not mRNA is transcribed and therefore whether or not protein is made at all, but they can’t change the amino acid sequence of the protein
True or false: Every person has two alleles of every autosomal gene, but in the human population some genes have many more than 2 different alleles
True
Tay-Sachs disease is caused by mutations in the HEXA gene, which encodes a subunit of the hexosaminidase A enzyme (HEXA). These mutations lead to loss of enzyme activity and a nerve cell-destroying accumulation of a fatty substance called GM2 ganglioside in the brain. What type of HEXA genetic variation would result in the biggest change to the protein produced?
4 nucleotide insertion 1278insTATC in the coding region of the gene
What DNA sequence would bind to the single-stranded sequence ATCGTT?
TAGCAA
What type of testing should be used for a single SNP associated with an increased risk of developmental dyslexia called rs761100. Having one or two C nucleotides at rs761100 increased a subjects’ odds of having dyslexia.
DNA sequencing of 1000 nucleotides including one SNP region
What type of testing should be used for 28 different SNPs in several genes associated with an increased risk of developing heart disease?
PCR followed by analysis by SNP chip
What type of testing should be used for if a child presents with neurological symptoms that could be associated with any of hundreds of different genetic mutations, each with dozens of alleles. Preliminary testing with known genetic markers has been inconclusive
Whole genome sequencing
What type of testing should be used for insertion of over 200 repeats of the sequence CGG in the FrM1 gene that causes fragile X syndrome which produces symptoms related to delayed intellectual development and speech?
PCR followed by gel electrophoresis
If a female genetic carrier of color blindness has children with a man without colorblindness, which of the following is TRUE?
The likelihood that a son will be colorblind is 50%
True or False: When an individual genetic variation impacts a complex trait, this variation typically has a relatively minor effect on the trait (phenotype).
True
