Genetics

Lamarck (1809) proposed a theory of the inheritance of acquired characteristics. He argued that biological features acquired by parents during their lifetime could be inherited by their offspring. He also theorised that individuals lose characteristics they don't require or use, and develop characteristics that are useful. Examples of what is traditionally called "Lamarckism" would include the idea that when giraffes stretch their necks to reach leaves high in trees, they strengthen and gradually lengthen their necks. These giraffes have offspring with slightly longer necks (also known as "soft inheritance")

Lamarck's ideas were for the most part rejected. However, no one could come up with a better idea until the work of Gregor Mendel. Darwin ended up accepting blending theory and doubting the widespread application of his own theory of Natural Selection. Blending means that all variability will eventually be eliminated. Nature needs something to select amongst, and if everything is the same (in blending theory, eventually everyone converges on their features and would end up being clones of one another) there is nothing to select.

Mendel's pea plant experiments conducted between 1856 and 1863 established many of the rules of heredity, now referred to as the laws of Mendelian inheritance. Pea plants are well-suited to breeding studies as they're self-pollinating, but its also easy to artifically control their fertilisation. Mendel chose pea varieties with clear-cut differences such as yellow peas and green peas.

Mendel's studies showed that when true-breeding different varieties were crossed to each other (e.g yellow pea and green pea), one in four pea plants had purebred recessive traits, two out of four were hybrids, and one out of four were purebred dominant. Cross-breeds always produced yellow peas, so Mendel proposed that yellow was a dominant trait. Yet, since yellow hybrids produced both yellow and green offspring, they must have carried the green trait, but unexpressed. Mendel suggested that each pea plant must carry a double dose of hereditary factors (alleles)

• AA = pure-bred yellow
• aa = pure-bred green
• Aa = cross-bred (since the A is dominant, yellow is outwardly expressed)

• Homozygote: organism that breeds true for a particular character (alleles are the same, e.g aa, AA)
• Heterozygote: organism that doesn't always breed true, having received different alleles from each parent (e.g Aa)
• Phenotype: visible, measurable characteristics
• Genotype: an organism's actual genetic composition. The same phenotype may have different genotypes (e.g yellow peas from Aa and AA)

Law of segregation: A gene may exist in 2 or more different forms (alleles). The 2 forms, one from each parent, separate during gamete formation - they do not blend. This allows recessive alleles to influence subsequent generations

Law of independent assortment: Inheritance of 1 gene is not affected by inheritance of another gene (e.g inheritance of flower colour is not linked to inheritance of pea colour). The biological selection of an allele for one trait has nothing to do with the selection of an allel for any other trait.

Law of dominance: Recessive alleles will always be masked by dominant alleles. Therefore, a cross between a homozygous dominant and a homozygous recessive will alwas express the dominant phenotype, while still having a heterozygous genotype.

Huntington's disease: Is an inherited disorder which results in death of brain cells. Huntington's is typically inherited from a person's parents, with 10% of cases due to a new mutation. The disease is caused by an autosomal dominant mutation in either of an individual's two copies of a gene called Huntingtin. The child of an affected person typically has a 50% chance of inheriting the disease. Symptoms usually begin between 30 and 50 years of age, but can start at any age. It is characterised by problems with mood and mental abilities, and jerky body movements.

Phenylketonuria (PKU): An inherited disorder due to mutations in the PAH gene. It is autosomal recessive, meaning that both copies of the gene must be mutated for the condition to develop. It's caused by an excess of the essential amino acid phenylalanine. It results in a unique form of mental retardation and can also include vomiting, seizures and hyperactivity. PKU affects about one in 10,000 to 25,000 babies. If one parent is a carrier, the children have a 50% chance of inheriting their recessive allele. They will also be carriers. If both parents are carriers, the children have a 25% chance of inheriting a double dose of the recessive allele, and thus having PKU. Treatment is with a diet low in food that contain phenylalanine.

Genes are functional segments of a long molecule called deoxyribonucleic acid (DNA). Each gene functions as a unit and codes for a particular product: a type of protein. Proteins are the major building blocks of bodies

Each non-sex human cell (i.e cells other than eggs or sperm) contains about 3 metres of DNA and approximately 25,000 genes. DNA is wound up tightly inside structures called chromosomes. Chromosomes are found within the nucleus of the cell. They are present in most, but not all cells (e.g red blood cells).

DNA is also found in mitochondria and plays an important role in mutations. Mitochondria are organelles in the cell that are crucial for energy production. Mitochondrial DNA is inherited solely from the mother. The 16,569 base pairs of mitochondrial DNA only encode for 37 genes.

Chromosomes are tiny rod-like structures. They are visible under a microscope only during cell division when dye is added to the cell. During cell division, they copy themselves and form their distinctive X shape.

Non-sex cells contain the diploid number of chromosomes (46 in humans, comprised of 23 pairs) - one set from each parent. Each gamete has a haploid number of chromosomes (23 in humans, one from each pair) - this is what the individual gets from each parent. 

When the egg and sperm combine, the fertilised egg (or zygote) has the complete complement of chromosomes, half from the mother and half from the father. Humans have 46 chromosomes. The number of genes in each chromosome varies (200-2000). X (sex chromosome): 800, Y (sex chromosome): 50.

Karyotype: full set of chromosomes in a person's cells. The number of chromosomes varies widely across different species. A fruit fly has 8, a dog has 78, and a goldfish has 100-104.

A male's X comes from his mother and the Y comes from the father. A female gets one X from each parent. Biological sex is determined by what the father passes on. Recessive sex-linked genes are more common males. Triple *** syndrome: female disorder with an extra X chromosome, child is typically physically and psychologically normal. XYY in males: typically have physical and psychological abnormalities.

Each gene is represented twice, one on each member of a chromosome pair, in the same locus (place) on the chromatid. The corresponding forms of genes are called alleles, and they can be alike (AA, aa) or different (Aa).

Some genetic disorders are based upon the inheritance of a particular combination of alleles, like Huntington's or PKU. Other genetic disorders occur at the level of the chromosome, so that there's either an extra chromosome, or a chromosome missing.

Down syndrome: DS is a chromosomal condition characterised by intellectual disability, characteristic facial appearance, and poor muscle tone. Occurs in around 1 of 740 newborns. Most cases are not inherited, but due to an error in cell division that results in 3 copies (instead of 2) of chromosome 21 being present in each of the body's cells.

Turner's syndrome: TS occurs in girls and is characterised by: short stature, extra folds of skin on the neck, underdeveloped breasts and reproductive organs, normal intelligence but poor in maths, and nonverbal (spatial) learning disabilities. Rather than 2 X chromosomes, 1 is missing or structurally altered.

Since some genetic disorders are based on specific alleles, its important to be able to locate genes on their chromosomes. A phenomenon called linkage violates Mendel's law of independent assortment, but helps us to map the location of genes on chromosomes.

Mendel's law of independent assortment: the inheritance of one gene is not affected by the inheritance of another genes (e.g inheritance of flower colour isn't linked to inheritance of pea colour). 

Linkage: the tendency for traits that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. 2 genetic markers that are physically  near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. 

Crossing over: the exchance of sections between pairs of chromosomes during meiosis.

All cell division (except for creation of gametes) occurs through mitosis. Mitosis occurs wherever more cells are needed. It produces 2 new cells that are identical to each other, and to the parent cell. Chromosomes are first doubled, then the chromatids are pulled apart. The chromosomes separate, and the cell divides into 2 diploid cells.

Meiosis is used to produce male and female gametes. Meiosis begins with a parent cell that is diploid, meaning it has two copies of each chromosome. The parent cell undergoes one round of DNA replication followed by two separate cycles of nuclear division. The process results in four daughter cells that are haploid, meaning they contain half the number of chromosomes of the diploid parent cell.

During meiosis, sections of the maternal and paternal chromosomes are swapped or crossed over. This results in unique recombinations of chromosomes from the mother and father. If genes are far apart from one another on a chromosome, they're unlikely to cross over together. The number of recombinations per 100 gametes can be used to estimate the distance between loci. Through this method, we know Huntington's is on chromosome 4 and PKU is on chromosome 12.

Chromosomes are made of double-stranded molecules of DNA. It contains the information needed to synthesise proteins. Each strand is a sequence of nucleotide bases attached to a chain of phosphate and deoxyribose. The 4 nucleotide bases are adenine, thymine, guanine, and cytosine. The 2 strands are bonded together by attraction: adenine - thymine. Guanine - cytosine.

Nucleic acids

• Ribonucleic acid (RNA) - contains uracil instead of thymine. Has a phosphate and ribose (sugar) backbone. Expression of genes
• Deoxyribonucleic acid (DNA) - contains thymine instead of uracil. Phosphate and dexoyribose backbones. Genetic code

Both RNA and DNA are long molecules made up of repeating units or nucleotides, which are formed of 3 components: sugar, phosphate, and a nitrogenous base. They both have alternating sugar and phosphate backbones. DNA forms a double helix. RNA forms a more simple string. 

Francis Crick & James Watson (1953) proposed a model for the structure of the DNA molecule, which showed how it could contain a long coded message. During replication, the 2 halves of the DNA ladder split apart. Each can then be used as a template to reconstruct the whole thing again. Free floating nucleotides (made by the cell prior to division) are attracted to their complementary bases. The basic unit of the genetic code are non-overlapping triplet sequences of nitrogenous bases (each called a codon)

With 4 different "letters" (i.e bases) being read in non-overlapping triplet sequences, there are 64 possible combinations or permutations. There are 2 types of "statements": 1 type specifies an amino acid and the other stops the transcription process (process of converting DNA to RNA). With 20 amino acids plus the need for a stop sign, the total number of statements needed is 21. Thus, most of the 64 possible messages in the triplet code are redundant and several have the same meaning.

DNA contains the code used to synthesise proteins. Proteins are molecules made up of chains of amino acids (simple organic compounds, N=20). A typical protein is made up around 100 amino acids. There are more possible configurations than the total number of atoms in the universe (Patterson, 1999).

All cells contain the exact same genes. Different cells develop because of differences in structural genes.

• Enhancers: stretches of DNA that determine whether specific structural genes initiate synthesis of proteins.
• Transcription factors: proteins that bind to the DNA and influence the extent to which genes are expressed. Many come from sources in the environment

Most of the DNA statements relate to amino acids. For example, the triplet AAA on DNA is transcribed in a complex process into the codon UUU. When that codon is read, the amino acid phenylalanine is added to a string of amino acids that will eventually form a particular protein