12.3C Laws of inheritance & variations Flashcards
Null Hypothesis
- is the commonly accepted fact
- it is the opposite of the alternate hypothesis
Hardy-Weinberg Principle
States that the allele frequency for dominant and recessive alleles remains the same in a population for many generations
p^2 + 2pq + q^2 = 1
p + q = 1 (p = A, q = a)
p^2 — AA
2pq — Aa
q^2 — aa
What is the gene concept?
A gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA
What is the function of gene?
Genes are a set of instructions that determine what the organism is like, its appearance, how it survives, and how it behaves in its environment
Structural genes
DNA segment that code for some specific RNAs or proteins.
Encoded for mRNAs, tRNAs, snRNAs, scRNAs
Functional sequences
regulatory sequences - occur as regulatory (initiation site, promoter site, operator site, etc.)
Nonfunctional sequences
introns & repetitive sequences.
Needed for coding, regulation and replication of DNA. Much more in no than functional sequences.
Gene
is a piece of DNA encoded information about the structure of one protein
Promoter
is a region of DNA that initiates transcription of a particular gene
is a sequence that binds to polymerase in the process of transcription initiation
Operator
segment of DNA being referred to when the repressor binds to it.
As a result, the transcription of certain genes is inhibited.
The switch is a segment of DNA.
Operon
is a functioning unit of DNA containing a cluster of genes under the control of a single promoter
is an area that special proteins can bind to, repressors that can reduce synthesis activity RNA from this gee, reduce its expression
Coding region
is the main structurally functional unit of a gene, contains nucleotide triplets encoding amino acid sequence
Terminator
a non-transcribed portion of DNA in the end of the gene at which RNA synthesis stops
is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription
What is gene expression in simple terms?
Gene expression is the process by which the heritable information in a gene, the sequence of DNA base pairs, is made into a functional gene product, such as protein or RNA
DNA (transcription) ⟶ RNA (translation) ⟶ proteins
Corepressor
a small molecule that cooperates with a repressor protein to switch an operon off
Tryptophan (corepressor) ABSENT
Repressor INACTIVE
Operon ON
RNA polymerase attaches to the DNA at the promoter ⟶ transcription happens ⟶ new mRNA is sythesised
Tryptophan (corepressor) PRESENT
Repressor ACTIVE
Operon OFF
tryptophan activates trp repressor ⟶ trp repressor binds to the operator ⟶ blocks attachment of RNA polymerase to the promoter ⟶ preventing transcription of the genes
Lactose ABSENT
Repressor ACTIVE
Operon OFF
the lac repressor is active ⟶ active lac reprossor binds to the operator ⟶ switches off the operon
Lactose present
Repressor INACTIVE
Operon ON
allolactose (inducer) binds to the lac repressor ⟶ alters its shape, inactivates repressor ⟶ RNA polymerase attaches to the DNA at the promoter ⟶ transcription happens ⟶ lac operon is transcribed into mRNA for the lactose-utilizing enzymes
Inducer
a specific small molecule that inactivates the repressor
Lactose PRESENT & Glucose SCARCE (cAMP level HIGH)
ABUNDANT lac mRNA synnthesized
glucose scarce ⟶ high level cAMP activates CAP ⟶ lac operon produces LARGE amounts of mRNA ⟶ enzymes in lactose pathway
Lactose PRESENT & Glucose PRESENT (cAMP level LOW)
LITTLE lac mRNA synthesised
glucose present ⟶ cAMP scarce ⟶ CAP is unable to stimulate transcription at a significant rate (repressor inactive)
Enhancer
groupings of more distant distal control elements
Action of enhancers and transcription activators
1) Activator proteins bind to enhancer in the DNA
2) A DNA-bending protein brings the bound activators cloer to a promoter (general transcription factors, mediator proteins, RNA polymerase II are nearby)
3) The activators bind to certain mediator proteins & general transcription factors, helping them form an active transcription initiation complex on the promoter
These protein-protein interactions facilitate the correct positioning of the complex on the promoter and the initiation of RNA synthesis
Epigenetics
is the study of heritable phenotype changes that do not involve alterations in the DNA sequence
Epigenetic change
is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state
The systems of epigenetic
-
DNA methylation
add methyl groups directly to DNA sequences -
histone modification (acetylation)
add or remove acetyl and methyl groups to histones within nucleosomes -
non-coding RNA (ncRNA)
leads to targeted mRNA degradation and inhibits gene expression
DNA methylation
the addition of a methyl group (CH3) to DNA, that cause major groove of DNA and inhibit transcription
Histone modification
involved in transcriptional activation/inactivation, chromosome packaging, and DNA damage/repair.
Histone acetylation occurs by the enzymatic addition of an acetyl group (COCH3) from acetyl coenzyme A.
condensed HETEROCHROMATIN:
DNA is SUPERCOILED and NOT accessible for transcription
EUCHROMATIN:
DNA is LOOSELY packed and therefore accessible to the transcription machinery
non-coding RNA (ncRNA)
is a functional RNA molecule that is transcribed from DNA but not translated into proteins
MicroRNAs (miRNA)
generally bind to a specific target messenger RNA with a complementary sequence to induce cleavage, or degradation or BLOCK TRANSLATION
Long ncRNAs
many lncRNAs can complex with chromatin-modifying proteins and recruit their catalytic activity to specific sites in the genome, thereby modifying chromatin states and influencing gene expression.
Mutation
is the permanent alteration of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA or other genetic elements
Mutations result from:
- errors during DNA replication (especially during meiosis),
- other types of damage to DNA (to radiation or carcinogens),
- which then may undergo error-prone repair (especially microhomology-mediated end joining),
- cause an error during other forms of repair,
- may cause an error during replication (translesion synthesis).
Point mutation
Missense mutation
Silent mutation
Nonsense mutation
Preventing mutations during replication
Enzymes:
- act as “spell checkers” correcting the errors (DNA polymerase)
Proof-reading:
- exonuclase activity corrects errors during the process of replication
DNA repair
Mismatch Repair:
- single base insertions and deletions are repaired by the mismatch repair mechanism
Nucleotide Excision Repair
- makes an incision
Direct Repair of Damaged DNA
- directly repaired by specialized enzymes without having to excise the nucleotide
Recombination Repair
- enables a cell to replicate past the damage and fix it later.
Error types & reasons
no bases = thermal or acid apurination
wrong bases = spontaneous or induction deaminization
base destruction = ionic radiation
dimers = UV-lights
non specific links = Mitomycin C
interval = Ionic irradiation, peroxides, nucleases
The Human Genome Project (HGP)
was the international, collaborative research program whose goal was the complete mapping and understanding of all the genes of human beings
Goals of HGP
- Obtain physical map of genome – Allows rough location of genetic fragments
- Develop sequencing technology – Increase throughput and reduce cost
- Obtain human DNA sequence – Achieve high accuracy, make freely accessible
- Analyse human sequence variation – Identify SNPs (Single nucleotide polymorphisms), develop theory
- Create bioinformatics tools – Develop databases and analysis algorithms
- Identify genes and coding regions – Develop efficient in-vitro or in-silico methods
- Sequence other model organisms – Bacteria, yeast, fruit fly, worm, mouse
- Ethical, legal and social issues – Develop policies and public awareness
HGP Medical applications
- Improved diagnosis of disease
- Earlier detection of predispositions to disease
- Rational drug design
- Gene therapy and control system for drugs pharmacogenomics ‘personal drugs’
- Organ replacement
Potential disadvantages or ethical objections
People may be put under pressure to not have children or terminate pregnancies
Increases pressure for germ line therapy to prevent children inheriting genetic conditions
May lead to discrimination with jobs
May lead to ‘designer babies’ with selection for specific fashionable/ on a whim characteristics
Knowing something might happen may cause psychological stress/ some may not want to know
Human rights/ personal freedom: instruction, infringement of civil liberties
Data protection issues: free access to your genetic information
