BIOL10008: Topic 3

Genetics

• Genetic information is stored in nucleic acids, predominantly DNA (Lectures 2 and 5, Topic 1)

• Genetics involves identifying the location of genes in a genome sequence

• Sequence changes caused by mutation can then be studied (Lecture 20)

DNA replication and cell division processes

• DNA is compacted into chromosomes (Chromatin = DNA + proteins)(Lecture 8, Topic 1)

• Semi-conservative replication of DNA (Lecture 9, Topic 1)

• Different chromosome structures exist pre/post DNA replication (Lecture 22)

• Cell division produces daughter cells with a compete set of genetic information (Lecture 9, Topic 1)

Genes are expressed to produce

• Genes are expressed to produce mRNA and protein products (Lecture 5, Topic 1)

Gene expression prokaryotes vs eukaryotes

• Transcription and translation occur simultaneously in prokaryotes (no membrane bound organelle of nucleus) but are spatially & temporally separated in eukaryotes

  (Lectures 2 & 8, Topic 1)

• Eukaryotic genes can include introns which are spliced out prior to translation

Gene products (RNA and proteins) perform biological functions like

• Enzymes

• Structural molecules

• Regulatory molecules

Genetic variation effects how

• Genetic variation can effect how gene products function (Lecture 20)

• The function of gene products gives rise to Biological characteristics (traits/phenotypes) that are influenced by genetic variation (Lecture 21)

Genetic variants are transmitted from cell to cell within an organism

• Gene variants are present in all cells of an organism

• Genetic information is faithfully copied and divided via DNA replication and mitosis (Lecture 9, Topic 1)

Genetic variants are transmitted to the next generation

Pedigree maps

Father passing trait on only to daughters

Genetic crosses - determining how gene variants contribute to traits

• Crosses between individuals with different variants can be performed

• Genetically hybrid progeny allow us to examine how different variants of a gene interact (dominance) to influence a trait (Lecture 21)

Genetic crosses - examine inheritance over successive generations

Genetic crosses - observe patterns of inheritance to create genetic models

Genetic inheritance involving multiple gene loci/traits

Control of gene expression

Mutations

are the primary source of genetic variation

• Mutations are a change in the sequence, structure or composition of the genome of an organism.

  • may/may not affect genes

  • may/may not be transmitted to offspring

Mutation creating positive and negative variation

Mutations are classified in multiple ways

How mutations occur

Whether or not they can be passed to offspring

Size/scale of the mutation

Locations within genes

Change to polypeptide sequence or abundance

Effect on gene function

Effect on fitness

Mutations can be spontaneous

Example 1. Error during DNA replication

At most one mutation per billion nucleotides

Example 2. Chemical changes to nucleotide bases such as Deamination (removal of an NH2 amino group)v

Mutations can be induced

• Chemical agents:

  • Nitrous acid: cause deamination

  • Benzopyrene: adds chemical group to guanine

• Radiation:

  • X-rays and gamma-rays can break sugar- phosphate backbone of DNA

  • Ultraviolet radiation can cause covalent bonds between adjacent thymine bases.

Germ line vs somatic mutations

Small scale DNA mutations

Mutations affecting one to a few nucleotides

• Point mutation or SNP (single nucleotide polymorphisms) – affect a single nucleotide

• Indels - Small insertions or deletions

• Microsatellite or SSLP (Simple sequence length polymorphisms) - a short sequence of 1-6 nucleotides with variable numbers of repeats

Large scale chromosomal mutations

Mutations affecting large regions or entire chromosomes

• inversion swaps within chromosomes and translocation swaps chromosomes

Where can mutations occur?

intergenic regions

include coding sequences (exons) and intervening sequences (introns) of genes that are transcribed into RNA

Non coding regions

(intergenic regions and introns) - can include regions important for gene expression and regulation

Coding sequences

those that are expressed as functional gene products

mutations within genes - how they effect the polypeptide

Silent mutations

Missense mutations

don’t know without further details

Nonsense mutations

truncated/shortened polypeptide

Frameshift mutations

huge change in amino acids

Effect of mutations on gene function - based on types of mutation

Genetic code - start and stop codons

redundancy - diff codon = same amino acids

Proportion of mutations beneficial vs deleterious

more bad than good

• More mutations are deleterious than beneficial

• Large-scale chromosomal mutations → can affect many genes or gene balance

• Small-scale DNA mutations (SNPs and indels) → can change important residues, large portions of the polypeptide or result in .truncated polypeptides

• Only very specific (and therefore rare) changes can give genes functions

Genotype

genetic composition of an individual

• ploidy

• locus (pl. → loci)

• allele

• homozygous or heterozygous (or hemizygous)

Phenotype

distinguishable biological property or trait

• observable OR measurable

• visible, physiological or molecular

• dominance relationships bw variants

Ploidy

number of sets of chromosomes

• independent of number of diff chromosomes an org has

Haploid

2 copies remain attached and each og stick is a chromatid (same whether haploid or diploid)

Diploid

both copies considered homologous although slight differences could be present

• 2 chromosomes remain attached and each og stick is a chromatid (same whether haploid or diploid)

Cycling between diploids and haploids

Locus

Location of specific gene or DNA sequence

Alleles

variant forms of a gene or DNA sequence at a locus

• not just binary - can be many variants at a locus (not just 2 types at each can be much more)

Locus doesn’t have to code for gene product

Can just look at individual loci as any DNA sequence to assess how many repeats (forensic analysis)

Same or different alleles (homozygous vs heterozygous)

Hemizygous

men will always be hemizygous

Example of what genotype looks like before and after replication in diploids

Relationship bw genotype and phenotype (easy to see in haploids)

Relationship bw genotype and phenotype with diploids

Dominant and recessive traits - what phenotype is observed in a heterozygote

black - dominant so capital D

brown - recessive so little d

Incomplete dominance

How incomplete dominance can work at molecular level

NEITHER is dominant over the either

Codominance

BOTH dominant or observed

Blood groups demonstrating codominance and dominance