Chapter 1 The cell as unit of health and disease Flashcards
how many base pairs are in the human DNA?
3.2 billion
how many protein coding genes are there?
20,000 making up 1.5% of the genome
this is an underestimate since multiple isoforms of genes exist.
how much of the human DNA is transcribed
85% with 80% being responsible for regulating the gene expression.
98.5% of the genome does not code proteins.
the non-protein coding region is responsible for?
- promoter/enhancer (binds transcription factors)
- Binding sites of proteins that maintain chromatin structures.
- Noncoding regulatory RNAs (micro-RNA and long noncoding RNA (never translated into proteins).
- mobile genetic elements (transposons) “jumping genes”
- Structural regions of DNA (telemores and centromeres)
what area is affected with polymorphisms?
the genetic variations of the non-protein coding regions of the genome. The area responsible for gene regulation.
how much of the DNA is identical between people?
more then 99.5% of human DNA is identical between 2 people.
2 common types of DNA variations in the human genome
- Single nucleotide polymorphisms (SNP)
- Copy number variations (CNVs)
feature of the single nucleotide polymorphisms?
- almost always biallelic (only 2 choices exist at a given site within the population (A or T).
- occur in exons and introns
- 1% occur in coding regions inline with the 1.5% coding regions of human DNA
- can occur in regulatory elements of the genome
- SNP can be neutral with no effect, but can serve as markers for disease-associated gene due to their proximity.
feature of the CNV (copy number variations)?
-responsible for upto thousands of base pair variations in the human genome and 50% of them are involved in gene-coding sequences.
define Epigenetics?
heritable changes in gene expression that are not caused by alterations DNA.
Gene expression is affected by?
- Chromatin Remodeling (147bp around a histone)
- DNA methylation; causes DNA condensation (silencing)
- Histone modifying factors…
What is chromatin?
- histones wrapped around with 147bp of DNA to form beads-on-a-string appearance of DNA. the have 2 forms;
1: HETEROchromatin: transcriptionally inactive
2: EUCHchromatin: trancriptionally active
what are Histone modifying factors?
- chromatin remodeling complexes: can reposition nucleosomes on DNA, thus exposing or silencing.
- Chromatin writer complexes: they mark histones via; methylation, acetylation, phosphorylation on specific AA.
- Chromatin erasers: removing of histone marks.
- Chromatin readers: bind histones with a particular marks, regulating gene expression.
what do different mark from chromatin writers do?
methylation
acetlyaltion
phosphorylation.
- methylation; on lysine and arginines causing either transcriptional activation or repression depending on which histone is marked.
- acetylation: (histone acetyltransferases) causes chromatin to open up.
- HDAC (histone deacetylases) reverse this process causing chromatin condensation.
- histone phosphorylation can cause opening or closing up of chromatin.
noncoding RNA types?
Micro-RNAs (miRNAs) 22 nucleotides in length.
Long non-coding RNA
micro RNA functions
silencing mRNA: takes advantage of this pathway for knockdown technology.
6000 miRNA genes, which can regulate multiple protein coding genes.
1st transcribed as pri-miRNA then cleaved into pre-miRNA which is then exported from the nucleus to be cleaved by DICER to miRNA.
The resulting single stranded miRNA associates RISC (RNA induced silencing complex) that either blocks ribosomes or cleaves the target mRNA leading to SILENCING.
Long non-coding mRNA function
about 30,000 of them in the human genome.
-they can bind to areas on the chromatin to repress the access to ribonucleoproteins.
-XIST is an X-chromosome linked gene that is responsible for X-chromosome repression.
many enhances are sites of lncRNA synthesis.
what is CRISPRs and Cas
"clustered regularly interspaced short palindromic repeats" Cas = CRISPR-associated genes this system in used by the acquired immunity of prokaryotes. Bacteria sample DNA of infecting agents, incorporating it into the host genome as CRISPRs. which is then transcribed and processed into an RNA sequence that binds and directs the nuclease Cas9 to a sequence (a phage) leading to its cleavage and the destruction of the phage. guide DNA (gDNA) is used to guide Cas9 to cleave double stranded DNA
proteins destined for the plasma membrane or for secretion go through what organelles?
the RER where they are synthesized
the Golgi where they are assembled
Proteins destined for the cytosol are synthesized where?
Free ribosomes
what does the smooth endoplasmic reticulum do?
its abundant in the in gonads and liver where it serves as the site of steroid hormone and lipoprotein synthesis as well as the modification of hydrophobic compounds such as drugs into water-soluble molecules.
organelles responsible for disposing of the cells own proteins?
- Proteasomes: “disposal” complexes cleave up tagged proteins in the cytosol, and are needed to end cellular processes and to present peptides to the major histocompatibility complex 1 for immunity.
- lysosomes; damage and unwanted phagocytosed microbes and damaged or unwanted cellular organelles are degraded and eliminated.
- Peroxisomes: contain catalase, peroxidase and other oxidative enzymes to breakdown of very long chain fatty acids making H2O2.
