Genetics

Assumed Knowledge The central dogma Basic genetic terminology DNA replication, transcription, translation Chromosome structure Mitosis and Meiosis Mendel’s laws of inheritance/ Hardy-Weinberg

The central dogma

Some Basic Terminology DNA – stands for deoxyribonucleic acid. DNA is a nucleic acid that contains the genetic material of a cell. DNA is composed of two strands of nucleic acids arranged in a double helix.

RNA – stands for ribonucleic acid. Involved in the conversion of genetic material in DNA to proteins. A single stranded sequence of nucleic acids.

Nucleic Acids – these are linear strands of nucleotides Nucleotides – these have three parts A phosphate group A sugar group A base

DNARNA Sugar DeoxyriboseRibose BaseAdenine (A)Adenine (A) Thymine (T)Uracil (U)Guanine (G)Cytosine (C)

Codon – these are sequences of three adjacent nucleotides Each codon encodes for a specific amino acid e.g. AAA will encode lysine, AGU will encode serine

Anticodon – these are sequences of three adjacent nucleotides that are complimentary to a specific codon Each codon encodes for a specific amino acid e.g. UUU will be complimentary to AAA and encode lysine, UCA will be complimentary to AGU and encode serine

Genome – the entire genetic content of an organism. Basically, all the DNA.

Genes – these are the regions of DNA that code for proteins. Not every bit of DNA gets converted to protein – DNA contains a lot of junk (~1.5% of the genome encodes for proteins) 1 Gene = 1 Protein

Chromatin – a complex of DNA and protein.

Chromosomes – These are large condensed segments of DNA formed from the condensation of chromatin. Each chromosome contains many genes. Humans have 46 chromosomes – 23 pairs

Karyotype – the number and appearance of chromosomes in the nucleus of a cell.

Allele – these are alternative forms of the same gene e.g. ABO blood groups There are 3 alleles that are recognised - A, B, O As every individual has two copies of there are six possible genotypes (combinations of the alleles) AA, AO, BB, BO, AB, OO

Genotype – this is the genetic make up of an individual e.g. is their ABO blood group AA, AB, BB???

Phenotype – this is an organism’s observable traits e.g. is their eye colour blue, green, brown

Alleles may be dominant or recessive Dominant alleles require only one allele of the two copies to be present for the phenotype to be observed Recessive alleles require both copies of the allele to be present for the phenotype to be observed

DNA Replication DNA is compose of two complimentary strands Sugar group and phosphate group form a backbone with the bases projecting into the center of the helix to form bonds with bases on the opposite strand Backbone reads as sugar, phosphate, sugar, phosphate

DNA strands have a 5’ and a 3’ end. This gives the strand directionality (a head end and a tail end!!!): 5’ > 3’ or 3’ > 5’ The two complimentary strands of DNA are arranged in opposite directions

In RNA uracil is the complimentary base to adenine, not thymine

DNA Replication Unwinding of the two strands of DNA (helicase) Each parent strand acts as a template for a new strand of DNA Formed by adding complimentary nucleotides (DNA polymerase)

Yields two identical strands of DNA, each with one old strand and one new strand Semi-conservative

Transcription & Translation Transcription DNA > RNA Translation RNA > Protein

Transcription Takes place in the nucleus Unwinding of the DNA strands Using one strand of DNA as a template, there is formation of a complimentary strand of messenger RNA (mRNA) RNA contains uracil instead of thymine All steps catalyzed by RNA polymerase

Splicing – this is the removal of the junk DNA Remember 1 gene = 1 protein Genes contain useful regions (exons) and junk regions (introns) Introns are removed from the mRNA by splicing Ensures only the exons carry on to translation and protein formation

Transcription Performed by the ribosome in the cytoplasm and also involves tRNA (transfer RNA) Every three nucleotides on mRNA will encode an amino acid (codons) tRNA contains a specific anticodon and also has attached an amino acid corresponding to that anticodon

tRNA anticodons bind to their complimentary sequences on mRNA The ribosome removes the amino acid attached to the tRNA and forms a chain of amino acids – a protein

Chromosome Structure & Number DNA wraps around specialised proteins called histones – beads on a string These condense to form chromatin (DNA + protein) Further condensation to form a compact chromosome

During the non-divided phase of the cell cycle DNA exists as uncondensed chromatin that is accessible for transcription During the dividing phase of the cell, chromatin condenses to form a four arm chromosome consisting of two identical sister chromatids joined in the center at the centromere Remember, DNA replication forms an identical copy of DNA – a chromatid is one of these copies

Humans have 46 chromosomes – 23 pairs 22 autosomal pairs 1 sex pair Females = XXMales = XY

Monosomy – one copy of the chromosome is missing Trisomy – an extra copy of the chromosomes is present

Mitosis and Meiosis Mitosis – cell division required for production of an identical set of chromosomes, forms two genetically identical diploid daughter nuclei Meiosis – cell division required for sexual reproduction, forms four genetically different haploid daughter nuclei Haploid (n) – only one copy of the chromosome is present Diploid (2n) – two copies of the chromosome are present, they exist in pairs

Cell Cycle Interphase – cell growth, protein production, DNA replication Nucleus division – via mitosis or meiosis Cytokinesis – division of the cytoplasm to form two separate cells

Mitosis Prophase – chromatin condensation to form chromosomes composed of identical sister chromatids. Formation of spindle fibers Metaphase – alignment of the chromosomes along the equatorial plane. Attachment of spindle fibers to the centromere of the chromosome Anaphase – shortening of spindle fibers pulls sister chromatids apart to opposite poles of the cell Telophase – formation of a new nuclear membrane around each chromosome group Pneumonic – Pour Me Another Tea

Meiosis – composed of meiosis 1 and meiosis 2

Meiosis 1 Prophase 1 - chromatin condensation to form chromosomes composed of identical sister chromatids. Formation of spindle fibers Recombination – chromosome crossover resulting in non-identical sister chromatids. Provides genetic variation in gametes Metaphase 1 Anaphase 1 Telophase 1

Meiosis 2 Prophase 2 Metaphase 2 Anaphase 2 Telophase 2 Cytokinesis There is no DNA replication during meiosis 2, this means each daughter cell will be haploid and only contain 23 chromosomes

Mendel’s Law of Inheritance Law of dominance – offspring that inherit a dominant gene will have only the dominant phenotype Law of segregation – during formation of the gamete, genes responsible for a trait are separated and only one is passed to the offspring. During fertilization, maternal genes are combined with paternal genes producing the genotype of that individual

In eye colour where the dominant gene is for brown eyes (B) and blue eyes are recessive (b), if both parents have the genotype Bb both will have brown eyes

Patterns of inheritance are Offspring may have brown eyes – BB, Bb or blue eyes – bb Bb BBBBb b bb

Hardy-Weinberg In a population with two alleles A (wild type) & a (defective) The frequency of the wild type allele is p The frequency of the defective allele is q As there are only two alleles p + q = 1 Chance that offspring are - AA is (p x p) = p 2 - Aa is (p x q) + (p x q) = 2pq - aa is (q x q) = q 2 A (p)a (q) A (p)AA (p 2 )Aa (pq) a (q)Aa (pq)Aa (q 2 )

Factors required for the Hardy-Weinberg equilibrium Large population No migration in or out of the population Random mating Mutation rate remains constant No selection of alleles