Inheritance 

Important definitions • Alleles – different forms of the same gene • Carrier – phenotypically normal individual with one normal (dominant) and one mutant (recessive) gene • Co-dominance – both alleles in heterozygous are expressed as they share a locus and are equally as dominant as each other • Dominant – an allele that is always expressed when it is present • Epigenetic – control of gene expression by modifying DNA or histones but not affecting DNA nucleotide sequence • Gene – sequence of DNA that codes for a polypeptide and occupies a specific locus on a chromosome • Genotype – all the alleles that an individual contains • Heterozygous – if the alleles for a particular gene are difference from either parent • Homozygous – if the alleles for a particular gene are the same from both parents 

Important definitions - continued • Linked – description of genes that are on the same chromosome and do not separate during meiosis • Locus – specific site on a chromosome where a gene is located • Monohybrid inheritance – inheritance of a single gene (plant height) • Mutation – a change in the amount, arrangement or structure in the DNA of an organism • Recessive – an allele not expressed in the presence of a dominant allele, only expressed if individual is homozygous recessive for that gene • Sex linkage – a gene carried by a sex chromosome so a characteristic it encodes is seen predominantly more in one sex • Test cross – crossed with homozygous recessive 

Monohybrid inheritance • Gregor Mendel and his pea plant experiment • Used pea plants because they are easy to grow, the flowers can self and cross pollinate and they produce a large amount of seeds (statistically significant) • Mendel studied contrasting characters because they are clear cut and easily distinguishable (discontinuous) as the genes are on different chromosomes • However, most characteristics are controlled by a number of genes such as human height, there is a range (continuous) 

Test crosses F1 generation > < F2 generation 

Co-dominance crosses Example of incomplete dominance > Gregor Mendel’s first law of inheritance: the characteristics of an organism are determined by factors (alleles) which occur in pairs. Only one pair is present in each gamete 

Dihybrid crosses 

Chi-squared test (x²) • Determines if there is a significant statistical difference between observed (O) and expected (E) results 2 = σ − 2 • Null hypothesis: there is no significant difference between observed and expected results • Degrees of freedom = no of phenotypes (no of sets of data) -1 • Unless told otherwise, test at 0.05 probability • If critical value > x², reject null hypothesis as there is a significant difference between observed and expected at (0.05) probability • If critical value < x², accept null hypothesis as there is no significant difference between observed and expected at (0.05) probability 

Linkage and sex linkage • Common phenotypes are due to linkage • Rare phenotypes are due to crossing over in meiosis (forming recombinants) • Some alleles are carried on the X chromosome (sex linked) • Y chromosome is much smaller so carries less alleles • Any recessive alleles carried on the X chromosome will be expressed in males as there is no dominant partner to counteract it • Males cannot pass the recessive X chromosome onto a son as they must have received the Y chromosome to be male • Any heterozygous female will be a carrier with a 50% chance of passing the recessive allele onto a son 

Mutations • May affect one gene or a whole chromosome • Occurs in body cells • Rate varies from species to specie but it is typically one mutation per 100,000 genes per population • Only mutations that occur in the formation of gametes are inherited • Organisms with short life spans and more frequent meiosis show a greater rate of mutation • Possible advantage as they add genetic variation to a population and may provide individuals with a selective advantage in it’s environment 

Gene mutations • Changes in the base sequence of DNA (deletion, insertion or substitution) • Deletion – nucleotide base is left out, not transcribe or translated resulting in a different amino acid being made • Insertion – nucleotide base added in, transcribed and translated resulting in a different amino acid being made • Often results in a different protein (usually an enzyme) being synthesised • Sickle cell anaemia • Replacement of one base results in the wrong amino acid being incorporated into two of the polypeptide chains in haemoglobin • Abnormal sickle shape cells carry less oxygen, resulting in anaemia (possibly death) • Mutant gene is co-dominant 

Chromosome mutations • Changes in the structure or number of chromosomes • Most likely to occur during meiosis, errors from chromosomes not being shared equally between daughter cells • Change in structure • Error occur during prophase I during the crossing over of chromosomes • Homologous chromosomes end up with different gene sequences making meiosis impossible • Change in number – Down’s syndrome • One daughter cell obtains 2 copies of a chromosome whilst the other receives none • Most common cause of Down’s syndrome is this happening to chromosome 21 • When fertilised, the zygote will receive 3 copies of chromosome 21 and a total of 47 

Factors affecting rate of mutations • Mutations occur naturally but the rate at which they occur may increase by mutagens (x-rays, gamma radiation, UV light, chemicals such as polycystic hydrocarbons in cigarettes, tar in tobacco smoke) • Mutagens can be carcinogens (cancer causing) • Most mutations are destroyed by the body’s immune system, if not a mass of cells forms (tumour) • Tumours are usually harmless (benign) but some invade tissues and travel around the body (malignant) and diseases caused by these are cancers • Proto-oncogenes stimulate cell division and Tumour-suppressor genes slow down cell division once enough cells have been produced for growth and repair • Mutations can cause proto-oncogenes to become oncogenes resulting in cells dividing too rapidly and causing a tumour or cancer to develop 

Epigenetics • DNA methylation – reduces/prevents gene expression • Cytosine base can have a methyl or hydroxymethyl group added • Methylated cytosine is read as cytosine and paired with guanine • Regions of DNA heavily methylated are less likely to be transcribed and their genes will not be expressed • Histone modification – increases gene expression/transcription • Histones (protein molecules DNA wraps around into nucleosomes) may be modified by adding an acetyl group to lysine, methyl group to lysine and arginine or phosphate group to serine and threonine • Alters the interaction with DNA, changing the arrangement of nucleosomes so the coiling of DNA is more relaxed, making it more accessible to transcription factors and RNA polymerase 

Consequences of epigenetic changes • Genetic imprinting – genes inactivated in gametes can transfer the inactivation to the next generation resulting in genes being permanently switched off by DNA methylation • X inactivation – whole X chromosome could be switched off, female mammals only use one X chromosome and the other is inactivated resulting in a mass of densely staining chromatin (Barr body) • Random inactivation of an X chromosome results in the patchwork fur colour of tortoiseshell cats as alternative X chromosomes are switched off in adjacent groups of cells • Autoimmune diseases • Diabetes • Mental illnesses • Many cancers