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

Base Adenine (A)Adenine (A)

Thymine (T)Uracil (U)

Guanine (G)Guanine (G)

Cytosine (C)Cytosine (C)

Codon – these are sequences of three adjacent nucleotides

Each codon encodes for a specific amino acide.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 acide.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 groupsThere are 3 alleles that are recognised - A, B, OAs 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

http://www.youtube.com/watch?v=zdDkiRw1PdU&feature=related

Transcription & Translation

TranscriptionDNA > RNA

TranslationRNA > 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

http://www.youtube.com/watch?v=erOP76_qLWA

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 = XX Males = XY

Monosomy – one copy of the chromosome is missingTrisomy – 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 nucleiHaploid (n) – only one copy of the chromosome is presentDiploid (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, Bbor blue eyes – bb

B bB BB Bbb Bb 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) = p2

- Aa is (p x q) + (p x q) = 2pq- aa is (q x q) = q2

A (p) a (q)A (p) AA (p2) Aa (pq)a (q) Aa (pq) Aa (q2)

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