Genome

• 2 types of Causative SNPs-

  • in the regulatory sequences of genes (non-coding SNPs)
  • in the coding regions of genes (coding SNP).
• Effects of non-coding SNPs: (located in the regulatory sequence)

  • changes amount of protein produced
• Effects of coding SNPs (located in the coding region within the gene):

  • changes amino acid sequence
• Most SNPs are located outside of genes. If SNPs are located close to a gene, they are referred to as linked SNPs and are inherited with the gene (i.e., the SNP and gene are less likely to be separated during crossing over).
• Linked SNPs have NO EFFECT on protein production or function.
• Variation in genomes range from single base pair variants to chromosome rearrangements.

  • There are 4 ways in which genomes between individuals vary:

  1. SNPs- Single Nucleotide Polymorphism
  2. STRs- Short Tandem Repeats (eg. CAGCAGCAG)
  3. InDels- small insertions and deletion
  4. Structural Variants.
• 2 types of SNPs:

  • Linked SNPs- are located outside of genes and are often inherited together with the gene its linked to (small distance).
  • Causative SNPs: located within a gene.
• STRs:

  • can be used to create genetic profiles, or “DNA fingerprints”.
  • For each STR site, an individual inherits 2 alleles, one from each biological parent. The alleles can be of different lengths (i.e., contain DNA sequences of different lengths/numbers of repeats).
• Genome sequencing:

  • To find all human genes
  • to identify the types and extent of variation in the human population.
• There are almost 20,000 human protein coding genes, and less than 2% code for proteins. There are no unique human genes and we still dont know what all genes do.
• All human are 99% similar at sequence level, regardless of race or ethnicity. African genome vary most.
• Variation is a key driver of evolution. Most variations is inherited, but each human also has their own small number of unique variants (eg. inherited errors.
• Knowledge of variation can help us tell:

  • which drugs work best in a patient
  • determine our close relatives
  • our species' origin (ancestry)
  • Crime solving
  • Disease risk/association
• SNPs vary commonly in the population. While some variants affect protein function, most do not.
• Modern Homo sapiens mated with both Neanderthals and Denisovans.
• Neanderthals:

  • 2-4% of the genome of non-African modern humans is made up of variants that arose in Neanderthals.
• DNA remains in the environment for a long time (under certain conditions for up to 1 million years). BUt is masked with modern DNA as DNA degrades.
• Humans and our close relatives:

  • Bonobos and chimps are the closest (living) relatives to humans.
• Gorillas and Humans:

  • The gorilla genome is missing a few human genes
  • All gorilla genes have a human equivalent
• Chimpanzees and Humans: Genome sequenced in 2005

  • There is a range of gene duplications between humans and chimpanzees
  • We share all our genes
• Denisovans:

  • ancient group of archaic humans.
  • discovered after a finger bone was found in Denisova which did not match DNA of modern day humans or neanderthals.
• Denisovan variation is also found in human genome. They are found in 4-6% of genomes of present-day Melanesians.
• Modern Day humans from Europe and Asia carry Neanderthal alleles. Those from Africa show NO sign of neanderthal alleles.
• Neanderthals :

  • are probably the closest relative (dead) of humans.
  • lived in caves 130,000-30,000 years ago in Europe and Asia.
  • often lived in caves which contributed to their DNA preservation.
• Comparative Genomics:

  • used to discover what is common and different between 2 species.
  • things in COMMOM are called CONSERVED and may encode biology in common between species.
  • things that are different may encode organism-specific biology.
• Aligning: Genome

  • helps compare 2 DNA sequences (from different species) to show similarities and differences.
  • Helps find out where differences occur.
• Difference during Aligning (Comparative Genomics) might be associated with:

  • Disease
  • Characteristics of an Individual
  • Evolutionary History
• Mutations:

  • in a single gene can have different effects (alleles).
  • majority have no no effect at all
  • outcome of mutation can also depend on:

  1. Environment effects
  2. Other genes (eg. genetic background)
• Dominant VS Recessive Alleles:

  • An individual can be heterozygous (with one mutant and one wild type allele).
  • can also be homozygous (both alleles are mutant).
• A dominant mutation is one that causes a phenotype when heterozygous.
• A recessive mutation causes a phenotype only when homozygous.
• Humans are diploid and inherit a copy of each gene from each parent (notwithstanding CNVs that can change copy number)
• Somatic cells acquire mutations if DNA gets damaged or copied incorrectly. Somatic mutations ARE NOT passed on to the next generation.
• Mutations that are inherited are called germline mutation and are passed on via the gametes.
• Mutation/ Variation is the driving force for evolution.
• Mutation:

  • can be beneficial
  • have no effect
  • have deleterious effect (harmful)
• X-linked Recessive:

  • no male-male transmission. This is given X must be from mum.
  • Most often affect males. As females have XX which means they have a backup, and for the phenotype to show mother must have 2 recessive alleles. Whereas, males only have 1.
• Autosomal Dominant:

  • Affected individuals have an affected parent.
  • Males and females equally likely to inherit.
  • occurs commonly in pedigree.
• Autosomal Recessive:

  • Typically not seen in every generation of an affected family.
  • Passed on by two asymptomatic carriers
  • males and females equally likely to inherit.
• Genetic determinism; the risk of you getting a particular disease is not simply whether you receive a particular allele from a parent but is a combination of variants and the environment.