Cell as A Unit of Health & Disease Flashcards
What is referred to as the gene complement of an organism
Genome
This sequence of letters
comprises the blueprint of the human body,
called
Human Genome
is the assignment of
genes to specific chromosomes (each of those
chromosomes have genes
GENOMIC MAPPING
The human genome contains roughly______________________
DNA base pairs
3.2 billion
Within the genome, there are about ___________________comprising only about 1.5% of the genome.
20,000 protein-encoding genes
Protein-encoding genes are the hollow
blocks of the human body.
Proteins like collagen, elastin, enzymes, etc
Worms are composed of fewer than 1,000 cells with genomes of only
about 0.1 billion DNA base
pairs - are also assembled using about 20,000 genes to produce proteins
What then is the difference between worms and
humans?
The answer is not completely known but the weight of current evidence suggests that much of the difference lies in the 98.5% of the human genome that does not encode protein
How much of the genome is used for the formation of proteins
Only 1.5%
Which parts of the genome provide architectural planning?
non-Coding Region
promoters and enhancers
NON- PROTEIN CODING SEQUENCES
Non-coding regulatory RNAs
○ Micro-RNAs
○ Long non-coding RNAs
Mobile genetic elements (ex. transposons)
jumping genomes- during evolution
Telomeres (chromosomal ends)
with every successive division of a telomere only it's chromosomal the end will be duplicated until it becomes short to senescent then undergo apoptosis.
Centromeres (chromosome “tethers”)
holds the chromosome together. A major component of centromeres is so-called satellite DNA, consisting of large arrays—up to megabases in length—of repeating sequences. It is also important in maintaining the dense, tightly packed organization of heterochromatin.
how much of the DNA is shared between 2 individuals
99.5%
The two most common forms of DNA variation are:
● Single nucleotide polymorphism (SNPs)
● Copy number variations (CNVs)
SNPs
● Variants at single nucleotide (nitrogen base +
sugar + phosphate) positions
○ A nucleotide is just a combination of 3
letters (CGA or TAT for example).
● If you change just one letter, for example instead
of CGA it becomes CGG, then there’s already a
DNA variation.
● Biallelic (only two choices exist)
○ Either a C or a G, an A or a T
They occur across the genome - with exons,
introns, intergenic regions, and coding regions
○ EXONS - coding region
○ INTRONS - non-coding region
SNPs occur in coding regions
1%
COPY NUMBER VARIATIONS (CNVs)
● Longer than SNPs. Instead of just one, series of letters were altered.
● can be biallelic and simply duplicated or, alternatively, deleted in some individuals
● Consists of different numbers of large
contiguous stretches of DNA from 1,000 base pairs to millions of base pairs.
epigenetics—
heritable changes in gene
an expression that is not caused by variations in DNA sequence
HISTONE ORGANIZATION
ll cells in the body contain same genetic material,
terminally differentiated cells have distinct structures and
functions. Different cell types are distinguished by
lineage-specific programs of gene expression. Such cell
type-specific differences in DNA transcription and
translation depend on epigenetic factors
What consists of Nucleosomes?
○ Nucleosomes consist of DNA segments 147 base pairs long that are wrapped around a central core structure of highly conserved low molecular weight proteins called HISTONES.
DNA-Histone complex
resembles a series of beads joined by
short DNA linkers and is called
CHROMATIN
what are the 2 types of chromatic and histones
Fine granular and Coarse
HETEROCHROMATIN
■ cytochemically dense and transcriptionally inactive (they are not transcribed) ■ Coarsely granular structures of the nucleus
EUCHROMATIN
■ cytochemically dispersed and
transcriptionally active
■ Finely granular structures of the
nucleus
how is a bone cell different from the neuron or any other cell
Remember that the nucleus of the brain cell will
have the same chromosome material as the nucleus of a bone cell or of a liver cell. But in a bone cell, the structures are not active so they are probably in heterochromatin.
Histone methylation
○ Both lysines and arginines can be methylated by specific writer enzymes; methylation of histone lysine residues can lead to transcriptional activation or repression, depending on which histone the residue is marked.
Histone acetylation
○ Lysine residues are acetylated by histone acetyltransferases (HATs), whose modifications tend to open the chromatin and increase transcription. In turn, these changes can be reversed by histone deacetylases (HDACs), leading to chromatin condensation.
Histone phosphorylation
○ Serine residues can be modified by phosphorylation; depending on the specific residue, the DNA maybe opened for transcription or condensed and inactive.
DNA methylation
○ High levels of DNA methylation in gene regulatory elements typically result in transcriptional silencing. Like histone modifications, DNA methylation is tightly regulated by methyltransferases, demethylating enzymes, and methylated-DNA-binding proteins.
Chromatin organizing factors
○ Much less is known about these proteins, which are believed to bind to noncoding regions and control long-range looping of DNA, thus regulating the spatial relationships between enhancers and promoters that control gene expression.
NON-CODING RNAs
Genes can also be regulated by noncoding RNAs. These genomic sequences are transcribed but not translated
how does transcribing different from the transcription?
Transcription and translation are
different. You may have a gene for the
production of collagen but it is not
translated. Meaning to say, collagen is not formed. Yes you have the gene for
that but it is not translated into protein
Micro-RNA (miRNA)
● Short RNAs (22 nucleotides on average)
● Do not encode proteins
● Functions primarily to modulate the translation of
target mRNA into their corresponding proteins
Posttranscriptional silencing of gene expression
miRNA is a fundamental and well-conserved
mechanism of gene regulation present in all
eukaryotes (plants and animals)
what happens if the oncogene is not silenced?
forms neoplasia
how many miRNA does the human genome code for?
6000, 30%.
This generates mature single-stranded miRNAs of 21 to 30 nucleotides that associate with a multiprotein aggregate called
RNA-induced silencing complex (RISC).
Small interfering RNAs (siRNAs)
are short RNA sequences that can be introduced
experimentally into cells where they serve as substrates for Dicer and interact with RISC, thereby reproducing endogenous miRNAs function
LONG NON-CODING RNA (lncRNA)
● The number of lncRNAs may exceed coding mRNAs by 10- to 20- fold ● Modulate gene expression in many ways: ○ Gene activation ○ Gene suppression ○ Promote chromatin modification ○ Assembly of protein complexes
what are the steps of cellular housekeeping
○ Protection from the environment ○ Nutrient acquisition ○ Communication ○ Movement ○ Renewal of senescent molecules ○ Molecular catabolism ○ Energy generation
PROTEASOMES
“Disposal” complexes that degrade denatured or otherwise “tagged” cytosolic proteins. ○ In antigen-presenting cells, the resulting short peptides are presented in the context of Class I or Class II major histocompatibility complex to help drive the adaptive immune respons
what is the composition of the cytoskeleton?
Microfilaments and microtubules
what is the importance of cytoskeleton?
to maintain polarity
ACTIN MICROFILAMENTS
○ 5 to 9nm diameter ○ formed from the globular protein actin (G-actin) ○ most abundant ○ G-actin monomers noncovalently polymerize into long filaments (F-actin) that intertwine to form double-stranded helices with a defined polarity. ○ New subunits are typically added at the “positive” end of the strand and removed from the “negative” end—a process referred to as actin treadmilling
INTERMEDIATE FILAMENTS
○ 10nm diameter ○ predominantly form ropelike polymers and do not usually actively reorganize like actin and microtubules ○ provide tensile strength so that cells can bear mechanical stress, e.g., in epithelia ○ They form the major structural proteins of skin and hair.
what filaments are the origin for poorly differentiated tumors
intermediate filaments
what are the filaments in mesenchymal cells?
Vimentin
muscle cells forms
the scaffold on which actin
and myosin contract.
Desmin
ritical for
neuronal axon structure and
confer both strength and
rigidity
Neurofilaments
is expressed in glial cells.
Glial fibrillary acidic protein
MICROTUBULES
○ 25nm thick
○ composed of noncovalently polymerized
α- and β-tubulin dimers organized into
hollow tubes
how is microtuble organizing center denoted?
”-“
This end elongates or recedes
in response to various stimuli by
the addition or subtraction of
tubulin dimers.
”+”
Kinesins - anterograde
(− to +)
Dyneins - retrograde
(+ to −)
