L20: Genetics and the DNA sequencing revolution

What is genetics

the study of inheritance patterns of biological variation within and between species

In which way are monozygotic twins identical

• genetically identical

• morphologically similar

what does DNA contain

• the information to synthesise proteins

• the information to make cells

• the information to make complex tissues

• the information to make whole organisms

in what year did the human genome project happen

1990 - 2001

how many base pairs were sequences in the human genome project

3,000,000,000

how much did the human genome project cost

$3,000,000,000

who was the first individual human to have genome sequenced

• Craig Venter

• 2007

• $10,000,000

How many base pairs could be sequenced per day in the 1970s

50,000

How many base pairs can be sequenced per day now

• due to new chemistry

• 3,000,000,000,000

the 1000 genomes project

• 2008 - 2012

• $4,000 genome

• 38,000,000 polymorphisms

What can tracing genomes do

• determine human susceptibility to infectious diseases

• track host response to infectious disease

• identify the cancer genome

• trace infectious disease outbreaks

• trace the microbiome

What will nasal metagenomics do

• announced in January 2023

• will sequence DNA from nasal swabs from respiratory disease patients and general population

• will provide diagnosis, track known viruses and rapidly identify new pathogens

What has been recommended by the Chief Medical Officer from 2016

research funders should require health research applicants to justify any research application that does not include genomic analysis

Which species can we sequence the genome of

• model organsims

• exotic and biologically interesting species

• agriculturally important species

• pathogens and their vectors

• extinct species

• ancient microbiomes

Genetic testing uses applications

• testing predisposition to common disorders

• pharmacogenomics

• stratified medicine

• personalised medicine

what have recent advances in DNA technology reduced

cost and time associated with sequencing complex genomes

what is still missing from genetic sequencing

we have lots of data but still large gaps in understanding

what does the future of genetic sequencing look like

• major impacts on health care

• revolutionising nearly all areas of biology

What does DNA encode for

All the information necessary to define the function of a single cell, tissue and whole organism

What does variation in DNA sequencing underly

the vast majority of the observes biological variation including human variation and disease

What provides insight into all areas of biology

understanding the information encoded within the genome

Applications of genetic technologies

• defining disease risk

• determining biological relationships

• identifying species and individuals

• manipulating the genome to create desirable products and phenotypes

What are the advancements in DNA sequencing technology revolutionising

the ability to understand the role of genetic variation in nearly every area of biology:

• human variation and disease

• drug response

• drug resistance

• cancer predisposition and evolution

• nature of the microbiome

• tracking infectious disease

• species diversity and conservation

Next generation sequencing

• Processes millions of DNA fragments simultaneously

• Sequences multiple strands simultaneously

• Low cost

• e.g. illumina, ion torrent

Third generation sequencing

• Reads longer DNA fragments

• Faster than NGS

• doesn’t require breaking DNA into small fragments

• e.g. MinION (Oxford Nanopore), PacBio

Oxford Nanopore Technology (ONT)

• uses nanopores to read DNA sequences in real time as strands pass through a biological pore

• portable (e.g. MinION is the size of a USB)

• Sequences ultra-long reads and can resolve complex genomes

Importance of sequencing projects

• Human Genome Project: gave the first complete reference genome but only represented 1 individual

• 1000 Genomes Project: provided more diverse sets of genomes from multiple populations

• Human Pangenome Project: Aims to capture greater genetic diversity, moving awat from a single reference genome

What biological questions are addressable vi genetic analysis

• Evolution (how life evolved, how species are unique, how humans migrated across globe)

• Health and Medicine (What causes genetic diseases, how people respond differently to drugs, can we predict and prevent disease)

• Disease (how viruses and bacteria evolve, how antibiotic resistance occurs, how some microbes are harmful and some beneficial)