Mandatory Course key areas and exemplification of key areas
 Cellular differentiation
- Cellular differentiation is the process by which a cell develops more specialised functions by expressing the genes characteristic for that type of cell.
- All cells contain the same genes. However, once the cell becomes differentiated, the only genes expressed are the ones needed to code for proteins specific for that type of cell. This is also known as selective gene expression.
 Somatic and germline cells
Somatic cells
- All differentiated cells with the exception of reproductive cells are known as somatic cells.
- Somatic cells form the main body tissue types:
- Epithelial: epithelial cells cover the body surface and line body cavities
- Connective: includes blood, bone and cartilage cells
- Muscle: muscle cells form muscle tissue
- Nerve tissue: nerve cells form nervous tissue
- The body organs are formed from a variety of these tissues.
- Somatic cells divide by mitosis to form more somatic cells.
- During cell division the nucleus of a somatic cell divides by mitosis to maintain the diploid chromosome number. Diploid cells have 23 pairs of homologous chromosomes.
- In somatic cells, any errors made during mitosis are not passed to offspring.
Germline cells
- Germline cells divide by mitosis to produce more germline cells or by meiosis to produce haploid gametes. (i.e. the only differentiation taking place in germline cells is towards the production of gametes)
- Mutations in germline cells are passed to offspring.
 Stem cells
- Stem cells are unspecialised cells that can divide by mitosis to make copies of themselves
(self-renew) and/or differentiate into specialised cells.
Types of stem cells
Embryonic stem cells.
-The cells of the early embryo can make all of the differentiated cell types of the body.
The inner cell mass cells of an early embryo (blastocyst stage) are pluripotent (they have the most potential) as they can make nearly all of the cell types in the body.
- These cells can self-renew, under the right conditions, in the lab. When grown in the lab scientists call these embryonic stem cells.
Tissue (adult) stem cells
- Tissue (adult) stem cells are involved in the growth, repair and renewal of the cells found in that tissue.
-They are multipotent. as they can make all of the cell types found in a particular tissue

type, e.g. red bone marrow and skin.
- For example, development of tissue (adult) stem cells in bone marrow (haematopoietic stem cells) into red blood cells, platelets and the various forms of phagocytes and lymphocytes.
- They have a much more limited differentiated potential as many of their genes are already switched off thus adult stem cells can give rise to a limited range of cell types.
Therapeutic uses of stem cells
- Examples: the repair of diseased or damaged organs, eg corneal transplants, bone marrow transplants and skin grafts for burns.
Research uses of stem cells
- Stem cells can also be used as model cells to study how diseases develop or for drug testing.
- Stem cell research provides information on molecular changes to explain how cell processes such as cell growth, differentiation and gene regulation work, thus providing a much deeper understanding on how gene regulation works and how drugs can interfere with these processes.
Sources of stem cells
- Sources of stem cells include embryonic stem cells, tissue stem cells and attempts to reprogram specialised cells to an embryonic state (induced pluripotent stem cells [iPS]).
Ethical issues with stem cells and the need for regulations of their use
- Embryos used for research must not be allowed to develop beyond 14 days, around the time a blastocyst would be implanted in a uterus.
- Regulation for the use of iPS cells.
 Cancer
- Cancer cells divide excessively to produce a mass of abnormal cells (called a tumour).
- These cells do not respond to regulatory signals and may fail to attach to each other.
- If the cancer cells fail to attach to each other they can spread through the body to form secondary tumours.
Extra: Cancer is an uncontrolled growth of cells. Healthy cells have various checkpoints at which their cycle is controlled. If mistakes are made they are normally encouraged to commit suicide. However in cancer cells, these checkpoints fail and as a result, they do not respond to any regulatory signals. Failures of these checkpoints could be due to genetic or environmental factors.

- All cells store their genetic information in the base sequence of DNA. The genotype is determined by the sequence of DNA bases.
- The genotype is determined by the sequence of DNA bases.
Structure of DNA
- nucleotides contain deoxyribose sugar, phosphate and base.
- DNA has a sugar–phosphate backbone, complementary base pairing — adenine with thymine and guanine with cytosine.
-The two DNA strands are held together by hydrogen bonds and have an antiparallel structure, with deoxyribose and phosphate at 3' and 5' ends of each strand.
- The arrangement of the two strands with their sugar-phosphate backbones running in opposite directions is known as antiparallel.
- Chromosomes consist of tightly coiled DNA and are packaged with associated proteins.
Replication of DNA
- DNA is the molecule of inheritance and can direct its own replication
- Prior to cell division, DNA is replicated by DNA polymerase
- DNA replication occurs at several locations on a DNA molecule.
- The requirements for DNA replication need to be explored.
- Replication of DNA by DNA polymerase and primer.
- DNA is unwound and unzipped to form two template strands.
- DNA polymerase can only add nucleotides to a pre-existing chain, so to begin to function a primer must be present.
- A primer is a short sequence of nucleotides formed at the 3’ end of the DNA strand about to replicate.
- The DNA chain is only able to grow by adding nucleotides to its 3’ end and that the reverse is true of its complementary strand on the right.
- DNA polymerase can only add complementary DNA nucleotides to the deoxyribose (3') end of a DNA strand. This results in one strand being replicated continuously (the leading strand) and the other strand replicated in fragments (the lagging strand) which are joined together by ligase.
- Only a fraction of the genes in a cell are expressed.
- Phenotype is determined by the proteins produced as the result of gene expression, i.e. it is determined by the proteins made by the genes which are “switched on” (expressed).
- Gene expression is influenced by intra- and extra-cellular environmental factors.
- Gene expression is controlled by the regulation of both transcription and translation.
Structure and functions of RNA.
- RNA is single stranded, contains uracil instead of thymine and ribose instead of deoxyribose sugar.
- RNA is also a type of nucleic acid but differs from DNA in a variety of ways.

- There are three different types of RNA molecules.
- mRNA involved in transcription carries a copy of the DNA code from the nucleus to the ribosome.
- tRNA involved in translation: Each transfer RNA (tRNA) carries a specific amino acid. tRNA folds due to base pairing to form a triplet anticodon site and an attachment site for a specific amino acid.
- rRNA associates with certain proteins to form ribosomes.
Transcription
- Transcription of DNA into primary and mature mRNA transcripts in the nucleus.
- RNA polymerase moves along DNA unwinding and unzipping the double helix and synthesising a primary transcript of RNA by complementary base pairing. Genes have introns
(non-coding regions of genes) and exons (coding regions of genes).
- The introns of the primary transcript of mRNA are removed in RNA splicing. The exons are joined together to form mature transcript.
- Splicing refers to the process of removing any introns before the transcribed molecule is translated.
Translation
- Translation is the synthesis of a protein under the direction of mRNA.
- mRNA is translated into proteins by tRNA at the ribosomes in the cytoplasm.
- mRNA consists of a series of base triplets called codons.
- Each anticodon carried by tRNA corresponds to a specific amino acid
- Each codon must be matched with its own anti-codon in the ribosomes.
- Triplet codons on mRNA and anticodons translate the genetic code into a sequence of amino acids. - Start and stop codons exist.
- Before translation occurs, the ribosome must bind to the 5’ end of the mRNA template so that the start codon can initiate the translation.
- Codon recognition of incoming tRNA, peptide bond formation and exit of tRNA from the ribosome as polypeptide is formed.
- Stop codons trigger the release of the polypeptide chain from the ribosomes.
Different proteins can be expressed from one gene
- This happens as a result of alternative RNA splicing and post-translational modification.
- Different mRNA molecules are produced from the same primary transcript depending on which RNA segments are treated as exons and introns.
- Post-translation protein structure modification: once translation is completed further modifications to the protein may be required. These are cleavage and molecular addition, e.g. cutting and combining polypeptide chains or by adding phosphate or carbohydrate groups to the protein.
Structures and shapes of proteins
- Proteins have a large variety of structures and shapes resulting in a wide range of functions.

- Amino acids are linked by peptide bonds to form polypeptides.
- Hydrogen bonds are formed during the folding process and cause the chain to become coiled or folded to form the three dimensional shape of the protein.
- Proteins are held in a three dimensional shape by peptide bonds, hydrogen bonds, interactions between individual amino acids.
- Separation and identification of proteins can be done by agarose gel electrophoresis.
Mutations and genetic disorders
- Mutations result in no protein or a faulty protein being expressed.
- Genetic disorders are caused by changes to genes or chromosomes that result in the proteins not being expressed or the proteins expressed not functioning correctly.
Single gene mutations
- Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of the substitution, insertion or deletion of nucleotides.
- The substitution, can result in missense, nonsense and splice-site mutations.
- missense (replacing one amino acid codon with another)
- nonsense (replacing an amino acid codon with a premature stop codon — no amino acid is made and the process stops)
- splice-site mutations (creating or destroying the codons for exon-intron splicing).
- Nucleotide insertions or deletions result in frame-shift mutations or an expansion of a nucleotide sequence repeat.
- These mutations have an effect on the structure and function of the protein synthesised and the resulting effects on health.
Chromosome structure mutations
- The structure of a chromosome can be altered by deletion (loss of a segment of a chromosome); duplication (repeat of a segment of a chromosome) and translocation (the rearrangement of chromosomal material involving two or more chromosomes).
- The substantial changes in chromosome mutations often make them lethal.