biology unit 2

what did project encode discover?

-a biochemical function can be assigned to 80% of the human genome -diseases often fall in noncoding portions of the genome -encoder helped to find the cell type that was associated with the specific disease -there are 18400 RNA genes and 20687 protein-coding genes -76% of the genome transcribed to RNA but not to proteins

how do oncogenes occur?

-if there are multiple copies of the gene so there is an excess of the protein and too much cell division OR -if the gene is moved to a new location in chromosome DNA and is under a new promoter regulation -> too much protein produced + too much division

what was discovered about epigenome changes and disease?

-it isn't single modifications to the epigenome that matter when causing diseases -combinations of modifications cause changes in gene expression -changes are associated with cancer or other disease emergence

why can't we relate disease to the proper area of the genome?

-key epigenetic changes occur in poorly understood regions of the genome -identifying locations of enhancers/genes that are affected is needed to find the link between epigenetic changes and disease

What are genes?

-physical and functional units of heredity -occurs at specific locations on chromosomal DNA -composed of base sequences to code for amino acids -encode the information used to generate the phenotype and are heritable -allele is one or two alternative forms of genes that arise from mutations

what are oncogenes?

-proto-oncogenes within DNA encode for a protein to stimulate cell division -oncogenes occur because of a mutation within this gene leading to a hyperactive growth-stimulating protein

what do NGS systems use?

-pyrosequencing -sequencing by synthesis -sequencing by ligation -ion semiconductor sequencing

what do enhancers normally do?

-they are activated through interactions with transcription factors that bind to specific DNA sequences within the enhancer region -those active in the epigenome areas to determine cell type are enriched in DNA sequences so cell type-determining transcription factors bind

how does sanger sequencing work?

1. DNA is amplified 2. DNA is separated using heat to denature the two strands 3. A primer (short piece of DNA) is used so DNA polymerase can add on nucleotides 4. When DNA has a primer, it is placed into four tubes for the sequencing reaction 5. Enzyme DNA polymerase is added to all four tubes 6. dNTPs are added to all four tubes (dATP, dCTP, dGTP, dTTP) 7. ddNTPs are added to the tubes to terminate the synthesis of the chain 8. Polyacrylamide gel electrophoresis is used to determine the strands sequence 9. tubes are poured into wells and the shortest fragments are observed floating the farthest down 10. Read from shortest to longest to figure out the complementary DNA sequence

What is the replication process?

1. bind helicase to separate the two strands 2. single strand binding proteins stabilize individual strands to prevent reconnection 3. primase synthesizes short RNA sequences as primers 4. DNA polymerase adds DNA nucleotides to the RNA primer 5. nucleotides attack through hydrogen bonds and DNA polymerase bonds the phosphates and deoxyribose sugars moves in the 5' to 3' direction towards helicase 6. okazaki fragments are created on the lagging strand since the synthesized strand isn't continuous 7. ligase seals the gaps and connects fragments

what is a mutation?

A change in the nucleotide sequence of DNA caused by replication errors or mutagens (radiation, chemical, etc.)

What are deletions or insertions?

A type of mutation that alters the reading frame of the mRNA so the nucleotides are grouped into different codons -can lead to significant changes in amino acid sequence downstream of mutation

How do nucleotides pair?

Adenine with Thymine Cytosine with Guanine

what is cancer?

DNA in single cells that acquire mutations causing them to continually divide

what is the central dogma of biology?

There is a one way flow of information from DNA to mRNA to proteins DNA->transcription->mRNA->translation->protein

what was the roadmap epigenomics project?

a follow up project to ENCODE that found 90% of DNA alterations were associated with diseases that lie in gene switching areas of the epigenome code rather than protein coding genes

what are monoclonal antibodies?

a form of immunotherapy where monoclonal antibodies bind specifically to certain proteins and deliver toxic molecules to trigger cancer cell death

What is DNA made of?

a phosphate group, a sugar (deoxyribose) and nitrogenous bases such as A,C,G,T

what is next generation sequencing (NGS)?

a platform that can sequence many genes simultaneously - the fastest and most cost effective method

what is the epidermal growth factor receptor (EGFR)?

a protein present on the cell surface that binds to epidermal growth factor so cells divide *there are abnormally high levels on the surface of many cancer cells causing them to divide excessively

what is a codon?

a sequence of three nucleotides and they each code for specific amino acids

what is the genetic code?

a set of rules which information encoded in specific base sequences of DNA that is translated into corresponding sequence of amino acids

what are signal transduction inhibitors?

a substance designed to blocks signals passed between molecules inside a cell that could affect the function of the cell including division or death -> potentially killing cancer cells

What is base substitution?

a type of mutation where there is replacement of one nucleotide with another -impact is dependent on whether there is an amino acid change that alters the protein function

What is DNA sequencing?

a way to obtain the entire sequence of nucleotides in a genome

what is a haplotype?

all SNPs found on a given chromosome

what happens in nondisjunction during meiosis I?

all gametes will have an abnormal number of chromosomes: half will have 2 copies of the chromosome pair that didn't separate and half will be missing copies of that chromosome

what is the origin of disease?

alterations in chromosome number and structure that come from accidents during meiosis

what was discovered about epigenome changes and their development?

changes in epigenomic areas during developmental transitions affect cell differentiation and interactions with transcription factors -ENCODE found hundreds of thousands of enhancer regions that regulate gene expression and development

what happens with a TSG mutation?

defective non functioning protein doesn't keep cell division under control so it disrupts the amount of transcription factors -> causing cancer

what are BRCA I and BRCA2 genes?

essential for repairing damaged DNA and normally expressed in cells of breast and other tissue

how did roadmap make their discovery?

examined 100s of cell types from healthy people and patients that were suffering from diseases, as well as fetal cells and stem cells -found millions of switches that control genes

what is epigenomics?

examines which factors act on individual genes and certain changes in the epigenome affect our health

what is nondisjunction?

failure of chromosomes or chromatids to separate during meiosis -during 1st division, both members of homologous pairs go to one pole -during 2nd division both sister chromatids go to one pole

what was project encode?

it characterized all functional elements in the human genome including genes, transcripts, and regulatory parts of the genome

How is DNA structured?

it is bound together in a double helix by hydrogen bonds the strands are antiparallel so one goes 5' to 3' and the other 3' to 5'

how are risks determined for personalized medicine?

molecular testing genomics proteomics metabolomics epigenomics family history and data mining

what is cancer genomics?

personalized treatment informed by assessment of patient's germline genome and genome of tumor *every individual tumor is distinct with regard to genetic alterations, but pathways affected in different tumors are similar *cancer genes function through dozens of signaling pathways and most are caused by 2-8 sequential alterations of 20-30 years

what is the phenomizer?

provides assistance in reaching correct diagnosis for patients because it has a database with 6000+ genetic variants and symptoms

what are enhancers?

regulatory DNA sequences that activate transcription of a gene or genes to higher levels

What was the human genome project?

requires multiple copies of the genome and then break it up into millions of fragments -sequence the fragments -pieces are aligned and matched up in fragment reassembly results: only about 21000 genes in 3.2 billion nucleotide pairs, only 1.5% of DNA codes for proteins, the rest is control regions, noncoding, and repetitive DNA

What is DNA?

the blueprint for living things in the form of a ladder tells amino acids how to form the right proteins

what is single nucleotide polymorphisms (SNPS)?

the foundation for personalized medicine since SNP profile tells patients the risk of developing certain diseases - ~5 million SNPs in the human genome

what is personalized medicine?

the idea that the right treatment can be determined for a particular patient at the right time - interventions targeted to individuals based on their risk

what are angiogenesis inhibitors?

they block the growth of new blood vessels to tumors

what are immunotherapies?

they boost the body's natural defenses to fight cancer using substances made by the body or in a lab -> triggers the immune system to destroy cancer cells ex: Car-T cells track cancer cells and destroy them and can be modified to carry cancer-fighting genes

what are tumor suppressor genes (TSG)?

they normally regulate cell growth

what was the goal of the human genome project?

to determine the nucleotide sequence of all DNA in the human genome and identify the location/sequence of every human gene

what is microbiome exploration used for?

to profile an individual's microbiome to detect, prevent, and diagnose infections or other diseases

what are hormone therapies?

treatment with synthetic or naturally derived hormones to add, block, or remove hormones to slow/stop cancer cell growth

what are the main cancer genes?

tumor suppressor genes and oncogenes

what happens in nondisjunction during meiosis II?

two of the four products will have a balanced number of chromosomes, one will have 2 copies of the same chromosome, and one will be missing any copy of the chromosome

what is pharmacogenomics?

using a patient's genetic profile to predict a drug's efficacy, guide dosage and improve patient safety

what are BRCA I and BRCA2 mutations?

usually insertions or deletions of some DNA base pairs in the gene and is the primary underlying cause of cancer and deficiency in DNA repair

what is known about cancer mutations?

usually occurs from an accumulation of mutations and is seen in somatic cells rather than germline (X/Y)