Human Molecular Genetics (L22-26)

Why was the human genome sequenced?

- identify all human genes and their roles
- analyse genetic variation between humans

What are the key findings of the human genome?

- Fewer genes than expected
- Less than 2% of our genome codes for proteins
- All humans are almost 100% similar at the sequence level
- Our genome is dynamic
- We still don't know what a lot of protein-coding genes do

How many genes are there in a genome and how is it split?

2% are coding (exon), 20% do not code for proteins (introns), and another 20% we do not know their functions. In total there are about 20,000 genes

Why is variation important in the human genome?

Evolution, diagnosing disease, determining the right drugs for a patient, and determining our close relatives/species origin

What are the four types of variation in the human genome?

- SNP's
- STR's
- InDel's
- CNV's

What are SNP's and describe the two types.

Common base pair changes, inherited by parents
There are four types of SNR's:
- Linked are on the outside of the gene and have no effect
- Causative have two effects: Non-coding causative SNP's changes the amount of protein produced
Coding causative SNP's change the amino acid sequence

What are STR's and describe them

STR's: repeats of nucleotides in specific regions of the genome in parent-inherited alleles. STR's can be used in genetic profiling

What are InDel's and describe them

Small insertions or deletions, also common variant type

What are structural variants/ CNV's and describe them

Structural variants: The genome is repeated sequences, and the CNV's are the amount of repeats between individuals

What is comparative genomics?

Is aligning two genomes and marking where the sequences are the same

Why is comparative genomics done?

Done to find differences like disease, characteristics, or evolutionary history

What does comparative genomics teach us about human biology within humans?

To identify variants related to phenotype

What does comparative genomics teach us about human biology within species?

To identify variants related to the biology of species

What does comparative genomics teach us about human origins?

Teaches us what our extinct relatives were

What are the different types of mutations in pedigree charts?

Inherited/germline
Acquired

What are inherited/germline mutations?

Are a permanent change in DNA sequence and are passed on to the next generation via gametes

What are acquired mutations?

Are a permanent change in DNA sequence in somatic cells, and are not passed on to the next generation

Explain loss of function and gain of function mutations

1: Breaking a gene so it doesn't work as well or not work at all
2: A gene works too well or do something unexpected

What are monogenic and polygenic diseases + examples?

Monogenic diseases: caused by a single gene mutation, i.e haemophilia, x-linked recessive
Polygenic diseases: Caused by combined effects of many genes, i.e obesity

What is determinism in genetics?

The idea that just having the related gene will not mean you will get the disease, as there are also environmental factors. Instead, genetics is probabilistic as opposed to deterministic

How do we get information about the function of genes from the phenotype (mutations)?

We can observe naturally occurring mutants and man-made mutants. In doing this we can work out exactly what the gene does

What is transgenesis and what is it used for?

Is adding foreign DNA into an organism to make a new protein or repair one. This is done to understand how genes work

How can we know if a gene variant is pathogenic?

We can modify the organism's gene by and observe that organism or its offspring.

What is one technique used to see if a gene is pathogenic?

CRISPR - Cas9 is where Cas9 protein with a guide RNA will reach the target DNA and make a double-stranded break. This break will cause the DNA to try and repair itself, but with errors because of the lack of a template strand, mutating the gene.

Outline gene therapy

Involves somatic cells, delivering DNA with functional copies, making more and more copies of functional DNA. This will not affect the next generation

Outline gene editing

Involves germline cells, embryos from at-risk families are screened and ensured that only healthy embryos are implanted. Mitochondrial DNA and Nucleus DNA switching.

Define tortipotent

Can give rise to any sort of cell

Define pluripotent

Cells that can give rise to most, but not all, of the body's cell types

Outline embryonic development

Embryonic development is the idea that the embryo begins as totipotent cells, and once gone through all the stages of embryonic development they become pluripotent

How do cells differentiate?

By switching on and switching off specific genes, causes that cell to only give rise to one specific cell despite all other genes still being present. Usually done via a protein.

What makes a stem cell different?

Stem cells are pluripotent

Differences between adult and embryonic stem cells?

1: Multipoint (only a few cell types)
2: Pluripotent

Why are stem cells important in modern medicine?

Useful in gene therapy (inserting RNA version of the normal allele to alter the gene code)
Useful in regenerative medicine (pluripotent stem cells to repair/replace damaged organs/tissue)