2.4-2.6 Biology Exam 2
What was the result of the Roadmap Epigenomics Project?
*not single modifications to the epigenome that matter in causing diseases. Combinations of modifications that cause changes in gene expression
What were contributing factors to epidemics?
- Demographic changes (population growth, inhabiting new areas) - Increasing contact with wild & domestic animals - 2/3 of EIDs originate from animals - Behavior (sexual, drug use, hygiene) - Poverty & social inequality - Climate & changing ecosystems - Travel, commerce & transportation
What are critical transitions for zoonotic diseases?
- Stage 1 to Stage 2: from animal to human - Stages 3 & 4: pathogen's ability to sustain cycles of human to human transmissions
Breast Cancer
- accounts for 1/3 cancer diagnosis - tissue dues not define the underlying genetic profile
Examples of Autosomal Dominant Disorders
- achondroplasia - alzheimer's disease - hypercholesterolemia - huntington's disease (a neurodegenerative disorder that affects muscle coordination leads to paralysis and dementia -> children with an affected father have a 50% chance of having the disease)
What does personalized medicine promise?
- advanced screening and early detection fo disease - prevention, proactive treatments, and lifestyle changes - safer, more effective medication and dosages that reduce side effects - develop better vaccines - lower healthcare costs
Examples of Autosomal Recessive Disorders
- albinism - cystic fibrosis - phenylketonuria(PKU) - sickle cell - tay-sachs - galactosemia (inability to fully break down galactose causing damage to liver, brain, kidneys, and eyes)
What are the research areas contributing to personalized medicine
- biomarker discovery - microbiome exploration - pharmacogenomics - clinomics - epigenomics
What are important characteristics of stem cells?
- capable of dividing to renew themselves - unspecialized or undifferentiated - can be induced to differentiate into blood, heart muscle, nerve, etc
What are BRCA1 and BRCA2?
- essential for repairing genes - mutations are usually insertions or deletions of a small number of DNA base pairs in the gene - are unrelated proteins, but both are normally expressed in the cells of breast and other tissue
What are omics?
- gen-omics - epigen-omics - prote-omics - interact-omics - metabol-omics
What happens when nondisjunction occurs during meiosis II?
- half will have the correct copies of the chromosome pair (n) - 1/4 will have an extra chromosome (n+1) - 1/4 will be missing a chromosome (n-1) **genetic abnormalities can result from an error in meiosis II
Examples of targeted cancer therapies
- hormone therapies - signal transduction inhibitors - angiogenesis inhibitors - immunotherapies - monoclonal antibodies
What are the goals of personalized medicine?
- improved health outcomes and qulity of life - greater effectiveness and efficiency pf healthcare delivery
What are the risks of personalized medicine defined through?
- molecular testing - genomics - proteomics - metabolomics - epigenomics - family history and data mining
What was learned from Project ENCODE?
-80% of the genome contains elements with biochemical function -RNA is a major functional unit of the epigenome -76% of genome transcribed to RNA not proteins -Evolution can occur by selection for RNA sequences that alter gene regulation
How does Shotgun Sequencing work?
1. a segment is cut many times at random 2. each seqment is sequenced with Sanger Sequencing 3. fragment is assembled with 10x redundacy
What are the types of stem cells?
1. embryonic stem cells 2. adult stem cells
How does CRISPR work?
1. identify the sequence to be modified (PAM) 2. guide RNA (crRNA and tracRNA) to find sequence 3. Cas9 protein attaches and assembles 4. double stranded break at PAM sequence
How does Next Generation Sequencing work?
1. nucleic acid extraction and isolation 2. library preparation 3. clonal amplification and sequencing 4. data analysis using bio informatics
How does the Sanger Sequencing Method work?
1. seperate the DNA into single strands using heat 2. make multiple copies of a segment 3. attach a primer 4. add to 4 polymerase solutions 5. grow complementary chains until termination dye 6. seperate the grown chains 7. electrophorese the 4 solutions
What was the timeline of the Human Genome Project?
1986- crucial meeting in Santa Fe 1988- project launched 2000- 1st draft 2003- complete version
When was the Human Genome Project completed and how much did it cost?
2003 and $3,000,000,000
What did the ENCODE project find?
90% of DNA alterations asssociated with disease lie in gene switching areas that code for the epigenome
What are adult stem cells?
Adult stem cells are found in differentiated tissue, such as bone or skin - they divide to replace damaged cells. No embryo is destroyed so there's no ethical issue. If adult stem cells are taken from the person to be treated, it will not cause rejection to the body.
How can we obtain the entire sequence of nucleotides in a genome?
DNA Sequencing like the Sanger Sequencing Method, Shotgun Sequencing, and Next Generation Sequencing
Examples of nondisjunction during meiosis I
Down Syndrome: an egg with two copies of chromosome 21 can be fertilized by a sperm with one copy of chromosome 21 (characterized by: susceptibility to disease, shortened life span, cognitive impariment, characteristic facial features) Turner Syndrome (sex-chromosome abnormality): an egg lacking a copy of the x or y chromosome can be fertilied by a sperm carrying a copy of the X chromosome (short stature, broad chest, and non-functional ovaries)
Enhancer activated through interactions with transcription factors
Enhancers active in epigenome areas determining cell type are enriched in DNA sequences to which cell type-determining transcription factors can bind. Changes in these areas during developmental transitions affect cell differentiation and interactions with transcription factors. ENCODE uncovered hundreds of thousands of enhancer regions in the genome that regulate gene expression and development.
What were the results of the Human Genome Project?
Exons (DNA codes for proteins) - 1.5% Repetative DNA (transposable elements) - 44% Repetative DNA (unrelated to transposable elements) - 15% Noncoding DNA - 15% Regulatory Sequences and Intron - 24.5%
Singles Nucleotide Polymorphism (SNP)
Foundation for personalized medicine -> patients know risks of developing diseases from personal SNP profile
Example of nondisjunction during meiosis II
Klinefeller Syndrome: a condition in which human males have an extra X chromosome (low testosterone and low fertility)
What is the super bug?
MRSA
Molecular Pathology v. Myriad Genetics
Patents. Naturally occurring sequences of DNA aren't patentable, but nonnatural DNA is. Made previous patents on natural DNA invalid. Patent law rewards invention NOT investment
What is synthetic biology?
a new interdisciplinary area that involves the application of engineering principles to biology **aims at the (re)design and fabrication of biological components and systems that do not already exist in the natural world
What is a stem cell?
a primitive cell with the ability to reduce inflammation, fight Apoptosis, differentiate into multiple tissues, and self replicate
What is Epidermal Growth Factor Receptor?
a protein present on the cell surface; binds to epidermal growth factor causing cells to divide
What does Autosomal Dominant mean?
a single copy of the mutated gene is enough to cause the disorder
How does cancer develop?
accumulation of mutations; most cancers associated with somatic cells which turnover frequently due to random errors in division
How do clinomics contribute to personalized medicine?
accurate interpretation of the data and using it to guide decisions about healthcare
What happens when nondisjunction occurs during meiosis I?
all gametes will have an abnormal number chromosomes - half will have two copies of the chromosome pair that failed to seperate - half will be missing copies of that chromosome
What is clonal amplification and sequencing?
amplifying DNA fragments by binding to ion surfaces, beads, or flow cells
What was Project ENCODE?
an international research consortium that aims to identify all functional elements in the human genome sequence.
What do signal transduction inhibitors do?
block the activities of molecules that participate in signal transduction
What do angiogenesis inhibitors do?
block the growth of new blood vessels to tumors
What are ddNTP and how is it used in Sanger Sequencing?
ddNTP are special nucleotides that are missing the hydroxyl on the 3' carbon. This blocks the DNA ploymerase from adding the next base and elongating the DNA chain
What do monoclonal antibodies do?
deliver toxic molecules cane cause the death of cancer cells **stimulate the patient's immune system to attack those specific cancer cellsWhate
What is an epidemic?
diseases that affect a large number of people in one area simultaneously
What is a pandemic?
epidemic that spreads over more than one area
What is nondisjunction?
failure of chromosomes or chromatids to seperate during meiosis
What is library preparation?
fragmenting DNA or RNA samples and adding specialized adapters
What are oncogenes?
genes that cause cancer/transform into a tumor cell under certain circumstances
What are zoonotic diseases/zoonoses?
infectious diseases that can be transmitted from other vertebrates to humans. May be direct or via a vector
What is the Sanger Sequencing Method?
method for determining the nucleotide sequence of DNA. It was developed by Fred Sanger whoe won the Nobel Prize 2x (1958- insulin protein sequence, 1980- DNA sequencing)
How do pharmacogenomics contribute to personalized medicine?
predict a drug's efficacy, guide dosage and improve patient safety
What is personalized medicine?
preventative, diagnostic, and therapeudic interventions targeted to individuals based on their risk
How do microbiome exploration contribute to personalized medicine?
profiles an individual's microbiome to detect, prevent and diagnose infections
What does a phenomizer do?
provides assistance in reaching correct diagnosis in patients with hereditary diseases
What was the Cancer Genome Atlas Project?
realization that there is not one cancer and one type of tumor; drugs must target specific profiles for a given individual **We can identify the epigenome associated with the specific cell type of a given individual's cancer
What was the Roadmap Epigenomics Project?
researchers examined 100s of cell types taken from healty people and patients suffering from diseases as well as fetal cells and stem cells
What do hormone therapies do?
slow or stop the growth of hormone-sensitive tumors, which require certain hormones to grow
What are embryonic stem cells?
stem cells from embryos that can differentiate into any specialised cell
What are epigen-omics?
study of epigenetic elements
What are metabol-omics?
study of function
what are prote-omics?
study of gene products
What are gen-omics?
study of genome sequences
What are interact-omics?
study of interacting molecules
What was the goal of the Genome 10k Project?
that goal was to sequence DNA of 10,000 vertebrates. **10k database currently includes genomes of more htat 16,000 vertebrate species
What is cancer?
the disease caused by an uncontrolled division of abnormal cells in a part of the body. **all cancers are derived from single cells and are gentic diseases
What was the goal of the Human Genome Project?
to determine nucleotide sequence of all DNA in human genome and identify the location and sequence of every human gene
What are Tumor Suppressor Genes?
transcription factors; mutations can cause cancer by disrupting the amount of transcription factors
What do immunotherapies do?
trigger the immune system to destroy cance cells
What does Autosomal Recessive mean?
two copies of the mutated gene must be present in order for the disorder to appear
What was the issue of the Roadmap Epigenomics Project?
was in relating disease to disruption of DNA function -> key epigenetic changes occur in poorly understood regions of the genome. **identifying locations of these enhancers and the genes they affect is necessary to understand the casual link between epigenetic changes and disease and designing targeted treatments
How do epigenomics contribute to personalized medicine?
which factors act on individual genes, and how certain changes in the epigenome affect our health
What does fertilization after nondisjunction yield?
zygotes with altered numbers of chromosomes