Includes the S-phase- DNA is synthesised. Period of growth in between cell division. Up to 90% of the cells time in the cell cycle is spent in interphase. It appears dormant but the activity level is high.

A point in G1 of interphase where cells are non-dividing (leave the cell cycle) but still metabolically functioning. Cells like Heart cells are always in G0.

Period prior to synthesis of DNA. For most cells this is where their major cell growth occurs. DNA in this phase is diploid (2n, 2 copies of the chromosomes) the genetic material is in the loose chromatin form.

G1 Restriction (R) point

Present at the end of G1. Dependant of levels of nutrients and energy it decides if cells will enter the cell cycle or move to G0.

S-Phase

Period where DNA is synthesised, creates 2 identical semi conservative condensed chromosomes (2 sets of chromosomes in this phase)

Final subphase of interphase. Right before mitosis. Microtubule formation, organelles produced, cytoplasmic volume increased. Replicated chromosomes are indistinct and nuclear envelope is intact.

G2 Restriction (R) point

Final check point before mitosis. Prevents cells from entering mitosis with DNA damage.

Mitosis

One diploid cell divides into 2 diploid cells with the same genetic information.

Prophase

Changes in nucleus, nucleosome disappears, chromosomes densify, spindle fibres begin to form, centrosome attaches to spindles and pull across forming an early form of the spindle bridge.

Prometaphase

Nuclear membrane breaks apart, spindle fibres attach to condensed chromosomes, begin to pull chromosomes to centre. Microtubules make contact with each other from opposite polls. Some microtubules attach to kinetochore. Spindle proteins pull chromosomes to centre.

Metaphase

Highly condensed chromosomes align in middle (Centromeres converge on the metaphase plate). Fully formed spindle fibres.

Spindle checkpoint

Monitors interaction between improperly connected kinetochores and tension.

Anaphase

Chromosomes move to opposite polls of cell. Initiated by protease which cleaves cohesion pulling sister chromatids apart.

Telophase

2 daughter nuclei form in the cell, the chromosomes unwind back into loose chromatin, nucleus reforms. Daughter nuclear envelope are formed.

Cytokinesis

Separate phase to mitosis, cytoplasm divides into 2 daughter cells, contractive ring formed by actin and myosin tightens around cytoplasm of cell and they are pinched apart.

Meiosis

Makes 4 haploid cells containing only one copy of each chromosome.

Meiosis 1

Membranes of a pair of homologous chromosomes physically associate. Goes through same stages as mitosis for round 1.

Prophase 1

Crossing over occurs sharing genetic information from 2 parent cells.

Metaphase 2

Unpaired chromosomes align at cells middle. No synthesis has occurred. So only 1 replicated chromosome remains so in anaphase sister chromatids have separated.

Law of independent assortment

When one trait is concerned a 3:1 ratio is observed if 2 traits are concerned a 9:3:3:1 ratio is observed.

Autosomal recessive

For rare traits, most affective individuals will have unaffected parents, all children of an affected parent are affected, risk of an affected child with homozygous parents for the trait is 25%

Autosomal dominant

Every affected personal has at least one affected parent. 2 affected individuals can have an unaffected child.

X linked recessive

Affected males receive mutant allele form their mother and transmit it to ALL daughters but no sons. Daughters of affected makes are usually heterozygous. Sons of heterozygous females have 50% change of being affected. Effect males more than females.

X linked dominant

Affected males produce ALL affected daughters and NO affected sons. A heterozygous female will transmit the trait to ½ her children. On average 2x as many daughters are affected.

Dominant lethal alleles

Rarely detected because they are rapidly killed. E.g. Manx cat.

Incomplete dominance

Both alleles blend effects together.

Codominance

Both alleles show effects but do not blend. Neither are dominant both expressed.

Epistasis

A form of gene interaction where one gene masks the phenotypic expression of another.

Pleiotropy

One gene influences multiple phenotypic traits

Genetic heterogeneity

When a single phenotype is caused by any one of multiple alleles or loci

Allelic heterogeneity

Different mutations with a single gene locus

Germline mosaicism

Presence of 2 or more populations of cells with different genotypes in one individual who has developed form a single fertilised egg.

Linkage

2 or more genes located on the same chromosome that do not show independent assortment and tend to be inherited together.

X chromosome

Humans use X Y sex chromosomes, only one X chromosome can be expressed at a time. Any other X chromosomes are inactivated.

Karyotype

A complete set of chromosomes from a cell that has be photographed during cell division (usually at metaphase)

Centromere locations

Metacentric- centrally placed. Submetacentric- a but uneven. Acrocentric- close to one end. Telocentric- at one end of the chromatid.

Polyploidy

A chromosomal number that is multiple of the normal haploid number. More than one full chromosome set.

Aneuploidy

Chromosomal number not exact multiple of haploid.

Triploploidy

3 times copy of autosomes

Tetraploidy

Four times copy of the autosomes.

Autoploidy

Each set is identical to parent set. Diploid genome. 2 sperms fertilising one egg.

Allotetraploid

Polyploid contains 4 haploid genes derived from separate species

Amphidiploid

Allotetraploid, where both original species are known

DNA

A right-handed double helix structure turning every 10 bases. With a phosphate group, a pentose sugar deoxyribose and a nitrogen containing base. A paring unstably with T and G pairing stably with C. 2 polynucleotides chains held together by hydrogen bonds.

Purine

The bases A and G

Pyrimidine

Bases C and T

Nucleoside

A nitrogen base and a sugar without a phosphate.

Nucleotide

A nucleoside plus a phosphate.

Polynucleotides

Nucleotides are joined together to make a chain. Are directional. Work form the 5 prime end to the 3 prime end with the hydroxyl group.

Telomere

Sequences at the end of chromosomes that play a critical role in chromosome replication. They keep chromosomes protected and prevent them from fusing into rings.

Aneuploidy

Change in number of individual chromosomes. Can lead to reproductive failure and birth defects.

Monosomy

One member of the chromosome pair is missing. Is lethal in humans.

Trisomy

One chromosome is present in 3 copies. Relatively common, most autosomal are lethal (50%). Down-syndrome is trisomy of chromosome 21.

Nondisjunction

Failure of homologues chromosomes to separate in meiosis, giving rise to aneuploidy.

Ames test

Used to test mutagenic compounds. Uses sensitive bacteria to show mutations. Uses salmonella typhimurium as it cannot synthesise amino acid histidine is very susceptible to mutations and more permeable than wild type bacteria.

Asymmetric transcription

Both DNA strands can be used as RNA templates the transcription direction is opposite to one another

RNA polymerase

Dependant on DNA for template, multi-subunit protein of approx. 480KD. There are 3 types found in eukaryotes. Binds to promotor.

Promotors

Directly bind to RNA polymerase. Are upstream of main part of gene and not transcribed. Have conserved sequences for example the TATA box as well as regulatory sequences that are recognised by transcription factors.

Transcription factors

Bind and recruit RNA polymerase. E.g. SPT, TFIID,TBP, regulate gene expression. Enhance, facilitate and stabilise and help create the transcription bubble.

Promoter clearance

After initiation RNA polymerase must clear the promoter.

Abortive initiation

The tendency for RNA polymerase to release RNA transcript and produce truncated transcripts.

The Ó factor

A protein needed for transcription in prokaryotes. Causes conformational changes to occur in core enzyme allowing for elongation.

Transcription

Creation of RNA strand form template DNA. has 3 phases. Initiation Elongation And termination.

Initiation

Promotor region is recognised by transcription factors and they bind to it to start transcription.

Elongation

RNA polymerase unwinds DNA through helicase activity the RNA polymerase incorporates nucleotides though complimentary base paring. RNA is synthesised as complex moves along the template DNA strand. The sequenced DNA re-joins, and the RNA disassociates.

Termination

Specific sequences in DNA signal the termination of transcription. They are encoded by polymerase. The RNA transcript is released from the DNA.

Termination In eukaryotes

Synthesised mRNA must be processed before is exported to cytoplasm. 3 steps. 1- A-7 methylguanine (MG) cap added to 5 -end. 2- A poly-tail is added to 3’ end. 3- intron sequences removed.

Exons- the coding sequences in mature mRNA.

The coding sequences in mature mRNA.

Introns

Non- coding regions of DNA. Are removed in intron splicing. Spliced out using RNA protein hybrids called spliceosomes. The intron segments are removed and remaining sequences are reattached. Remaining DNA will be exon only.

Translation

Occurs in cytoplasm on ribosomes. 2 ribosomal subunits small subunit binds to mRNA and large to tRNA also has enzyme to form peptide bonds. 3 steps. Initiation- AUG start codon recognised my methionyl-tRNA. 2- Elongation, ribosome incorporates amino acids into polypeptide chains, RNA decoded by tRNA and transcribes specific amino acids into chain. Transfer RNA tRNA is used as adaptor between an amino acid and mRNA codon. Translates tRNA sequences to codons that signify amino acids. tRNA binds to specific amino acids by aminoacyl-tRNA synthase. 3- Termination, ends with stop codon, UAA, UAG or UGA.

Point mutations

Substitution of a single base with another base nucleotide. Insertions or deletions. Cause frame shifts.

Silent mutations

Base substitution that does not change amino acid encoded.

Missense mutation

Base changes amino acid, can be harmless but some can be harmful like recessive lethal allele.

Nonsense

Base substation that changes amino acids into stop codons. Catastrophic. Shortens proteins

Sense mutations

Base change convers stops into sense codons lengthens proteins.

Trinucleotides repeat diseases

Genetic diseases characterised by presence of unstable and abnormal expressions of DNA in triplets, can inactivate a gene or result in a toxic protein.

Loss of function mutations

Impedes function. Most are recessive. Ones in trans or cis sites are always expressed. If found in lac 1 gene or in operator gene e can result in constitutive expression of lac Z.Y and A genes regrades of presence of lactose.

Null mutations

Completly abrogates function.

Chemical mutagens

Are base analogues and are incorporated into DNA. cause mispairing during DNA replication leading to mutations. Or can be base modifiers are alkylating agents transferring alkyl groups to nucleotide bases E.g. mustard gas. Intercalating agents fits in between bases caused DNA to unwind to fit can make good nucleotide acid stains.

Post replication repair

DNA replication may skip over a lesion such as a thymine dimer. Through recombination the correct sequence can be inserted into the gap.

Base exclusion repair

Corrects DNA that is damaged. DNA glycosylase recognises broken base and binds between bases and sugar. Cuts sugar with missing base recognised by AP endonuclease that makes the cut. The gap is filled by DNA polymerase and signal ligase.

Nucleotide exclusion repair

Repair bulky lesions that alter the double helix. Including UV induced thymine dimers. Usually a specific number of nucleotides are clipped on either side of lesion.

Double stranded break repair

Uses homologues recombination. Uses sequence complimentary on sister chromatin. Double stranded breaks caused by ionising radiation.

Ames test

Constitutive- genes that are always on, usually housekeeping genes.

Genes that are always on, usually housekeeping genes.

Inducible

Only turned on as needed. Structural genes and enzymes.

Operons

Are sections of DNA that contain a cluster of genes under control of a single promoter. They contain the sequence that control transcription (in eukaryotes).

Polycistronic mRNA

One mRNA mol translated into separate proteins

Lac operon

Proof of principal in E.coli. negative control of inducible gene expression a repressor operator interaction. Positive control uses CAP that depends of the sugar glucose. RNA binding not efficient under lack control without CAP. Binds to promoter, binding of CAP requires CAMP. If glucose if low CAMP is high. Glucose inhibits adenyl cyclase decreasing CAMP.

Lactose

RNA polymerase is inhibited in the presence of lactose. Sugar binds to repressor causing a conformational change to the molecule. Repressor operator interaction readies structural gene to be translated. In absence of lactose the repressor gene encodes a molecule that blocks transcription of structural genes.

Lac Z gene

Encodes the enzyme b-galactosidase that cleaves the disaccharide lactose into a monosaccharide