Application of reproduction and genetics

• Genomics is the study of the structure, function, evolution and mapping of genomes
• Main goals of the Human Genome Project:

  • Provide a complete and accurate sequence of the 3 billion DNA base pairs in the human genome
  • Identify all genes in the human genome and find the location of each gene
• The Human Genome Project aimed to:

  • Help understand diseases to improve diagnosis and treatment
  • Identify mutations linked to different forms of cancer
  • Improve medication design
  • More accurately predict the effects of drugs
  • Improve disease risk assessment
  • Advance forensic applied sciences
  • Use in bioarcheology, anthropology, and evolution
• Sanger Sequencing:

  • Initially, the process took a long time and focused on a small number of DNA samples
  • The first human genome took 13 years to prepare (approx. 3 billion bases) using this technique
• Next Generation Sequencers (NGS):

  • NGS are modern versions of Sanger Sequencing, producing a base sequence for a whole organism in a few hours
  • Several methods of NGS add labelled bases to a growing chain of nucleotides, many of which can be analyzed simultaneously
  • NGS is significantly cheaper, quicker, needs less DNA, and is more accurate and reliable than Sanger sequencing
• In Sanger sequencing, a large amount of template DNA is needed for each read, while in NGS, a sequence can be obtained from a single strand
• NGS is quicker than Sanger sequencing because the chemical reaction is combined with the sequencing, unlike in Sanger sequencing where these are two separate processes
• In Sanger sequencing, a maximum of ~1kb can be analyzed at a time, whereas in NGS, about 300Gb of DNA can be sequenced in the same run
• NGS is more automated, uses fewer resources, is faster, and costs less compared to Sanger sequencing
• The first human genome sequence cost around £300 million, while using modern Sanger sequencing methods, a full human genome would still cost £6 million. Sequencing a human genome with NGS today would cost only £6,000
• The 100K Genome Project aims to sequence the DNA of 100,000 people in the UK
• NGS technology enables the 100K Genome Project to reduce cost and time in sequencing DNA
• The project will allow scientists to study variation in the human genome
• The 100K Genome Project focuses on diseases like rare cancers
• Unlike the Human Genome Project, data in the 100K Genome Project is not anonymous; participants give informed consent for the use of their data
• Aims of the 100K Genome Project include:

  • Improve the accuracy of diagnoses
  • Better predict the action of drugs
  • Improve the design of drugs
  • Find new ways of treating genetic diseases
  • Explore tailoring therapies to treat a disease in an individual person
• Genetic screening can now identify a large number of defective genes
• Genes like Alzheimer’s disease, Huntington’s Chorea, and certain cancers may only manifest their effects in adults
• Screening for genes like these could help doctors prepare for future issues and allow patients to plan ahead, especially for conditions with no treatments and are fatal
• Concerns exist regarding discrimination and social stigmatization outweighing the benefits of genetic testing
• There is a fear that insurance companies and some businesses might discriminate against individuals based on their genotype, affecting employment and insurance opportunities
• Advantages of genetic screening following the Human Genome Project:

  • Can identify carriers of genetic disease
  • Provides genetic counselling
  • Screens embryos prior to implantation
  • Assesses future risk of developing a condition
  • Checks a foetus during pregnancy to detect disorders like cystic fibrosis, Huntington’s disease, and thalassaemia
• Disadvantages of genetic screening following the Human Genome Project:

  • Not always accurate
  • No cure for most conditions, causing stress for gene carriers
  • Misuse of personal genetic information by entities like insurance companies, private health care, and employers leading to discrimination
  • Risk of stigmatization for individuals with identified genes
  • Concerns about routine screening for adult-onset disorders like Alzheimer’s disease and some cancers
  • Potential use to select embryos for non-medical purposes, such as specific characteristics
• Sequencing the genome of chimpanzees and other primates helps determine evolutionary relationships between primate groups and aids in conservation efforts
• Malaria, caused by the protoctistan parasite Plasmodium and transmitted by the mosquito Anopheles gambiae, is one of the biggest killers globally
• The genome of Anopheles gambiae has been sequenced to control malaria, as it is the vector that transmits the Plasmodium parasite to humans
• Control of mosquito populations, crucial in managing malaria spread, has been achieved by using insecticides, but many mosquitoes are now resistant
• Sequencing the mosquito genome aims to edit out resistance genes, potentially rendering male mosquitoes sterile to reduce populations in malarial areas
• One ethical concern is the potential ecological impact of rendering mosquitoes sterile, affecting organisms dependent on mosquitoes for food and potentially leading to mosquito extinction
• Mosquitoes are vectors of diseases like the Zika virus, so controlling their population can help manage the spread of mosquito-vectored diseases
• The Plasmodium parasite causing malaria has also been sequenced to develop effective drug treatments, as resistance to traditional chloroquine drugs is spreading rapidly
• Artemisinin drugs are being used in combination with others to combat malaria resistance, and sequencing the Plasmodium genome aims to render the parasite susceptible to drug treatments
• Each human (apart from identical twins) contains a unique sequence of bases in their genome, known as a "genetic fingerprint," which can be used in forensic science and paternity testing
• A gene is composed of regions that are translated – exons and introns, with repeating base sequences between exons that are not translated
• The number of repeats of base sequences in introns, called short tandem repeats or STRs, is variable between individuals
• In a genetic fingerprint, a variety of these STRs are analyzed to produce a unique pattern based on the number of times each STR is repeated
• Forensics use the characteristic pattern of bands in genetic fingerprints to identify individuals from sample materials, such as victims and suspects, requiring an exact match of banding patterns for identification
• DNA samples for genetic fingerprinting could be from sperm cells, white blood cells from blood smears, skin cells, or hair follicles, sometimes requiring amplification for analysis
• In paternity cases, the technique relies on the fact that the STRs are inherited, with a child inheriting some bands from its biological father and some from its mother
• Markers of known length run alongside the fingerprint DNA to provide fragment size and position, forming a DNA ladder