Genetic Disorders, Gene Therapy, Selective Breeding, and Bioinformatics

Genetic Disorders

• A genetic disorder is a disease caused by a change, or mutation, in an individual’s DNA.
• Some genetic disorders are carried by a dominant allele, while others are carried by a recessive allele.

Mutation

• A mutation is a change in the DNA sequence of an organism.
• Mutations can occur due to errors during DNA replication or environmental factors.

Commonly Known Genetic Disorders

• Examples include diabetes, cancer, epilepsy, Down syndrome, Turner syndrome, hemophilia, cystic fibrosis, and albinism.
• Genetic disorders are further categorized as:
  • Autosomal dominant
  • Autosomal recessive
  • X-linked
  • Chromosomal
  • Multifactorial disorders

Categories of Genetic Disorders

Genetic disorders can be grouped into three main categories:

I. Single-Gene Disorders (Monogenetic Disorders)

• Caused by defects in one particular gene due to changes or mutations in the DNA.
• The pattern of inheritance depends on whether they are controlled by genes on autosomes or by genes on sex chromosomes.

Mendelian Inheritance Patterns

The three major patterns of Mendelian inheritance for genetic disorders and diseases are:

• Autosomal dominant
• Autosomal recessive
• X-linked

A. Autosomal Dominant

• Expressed in the heterozygous condition.
• Controlled by genes on one of the 22 pairs of human autosomes (non-sex chromosomes).
• Inherited in the same way regardless of the sex of the parent or offspring.
• Example: Huntington's disease, a progressive neurodegenerative disorder.

B. Autosomal Recessive

• Expressed in homozygous conditions.
• Most commonly occur when both parents carry the trait and the offspring receives the defected gene from each parent.
• Both parents are carriers of the trait but are unaffected.
• Examples: Cystic fibrosis and Albinism are autosomal recessive disorders controlled by a single autosomal gene with two alleles.

C. X-Linked Disorders

• Controlled by genes on the sex chromosomes.
• Example: Hemophilia, a blood-clotting disorder.
• X-linked recessive disorders are less common in females than in males.

II. Chromosome Disorders

• Result from changes in the number or structure of chromosomes.
• Occur due to errors during cell division.
• Example: Down syndrome or trisomy 21 $(2n+1)$, which occurs when a person has three copies of chromosome 21.

Types of Chromosome Disorders:

• Aneuploidy: Wrong number of chromosomes (e.g., $(2n-1)$, $(2n-2)$, $(2n+1)$, $(2n+2)$).
• Deletion: A part of a chromosome is missing.
• Inversion: Two breaks on a chromosome, and the segment between the breakpoints flips around and reinserts back into the chromosome.
• Translocation: A rearrangement of a chromosomal segment from one location to another.

III. Multifactorial Disorders

• Complex disorders caused by changes in the combination of multiple genes.
• Complex interaction with environmental and lifestyle factors such as smoking, drinking alcohol, eating an unhealthful diet, not getting enough sleep, and living in an area with high levels of air pollution.
• Examples: Diabetes and cancer.

Genetic Testing and Counseling

Genetic Testing

• A type of medical test that identifies changes in genes, chromosomes, the genome, or proteins.
• Important to identify the type of the disorder.
• Examines the genetic material and informs an individual about the likelihood and risk of passing genetic disorders on to children.
• Identifies the likelihood of parents passing a genetic disease or disorder to their children.
• Examines if there are any changes in our DNA that can inform us of the well-being of our health and our family.
• Examples of diagnostic tests during pregnancy: Amniocentesis and chorionic villus sampling.

Genetic Counseling

• The process of checking a family with regard to medical history and medical records.
• Ordering genetic tests.
• Evaluating the results of these tests and recording them.
• Helping parents understand and reach decisions about what to do next.
• Helps to make informed decisions about genetic testing.
• Gives information about how genetic disorders might affect one’s family.
• Increases understanding of genetic disorders that are inherited in the family.
• Used to solve different psychological and social impacts.

Gene Therapy

• The technique that introduces genes into existing cells to modify a person’s genes to prevent or cure a wide range of diseases.
• A promising treatment option for a number of diseases.
• The promising development: treatment of a brain tumor.

Types of Gene Therapy

Depending on the types of cells being treated:

• Somatic gene therapy: Transferring a section of DNA to somatic cells; the effects will not be passed onto the patient’s children.
• Germ line gene therapy: Transferring a section of DNA to sex cells; the effects will be passed onto the patient’s children and subsequent generations.

Mechanisms of Gene Therapy

• Replacing a disease-causing gene with a healthy copy of the gene.
• Inactivating a disease-causing gene that is not functioning properly.
• Introducing a new or modified gene into the body to help treat the disease.

Types of Gene Therapy Products

• Plasmid DNA: uses DNA molecules to carry curative genes into human cells.
• Viral vectors: uses modified viruses as vectors (vehicles) to carry curative genes into human cells.
• Bacterial vectors: uses modified bacteria as vectors (vehicles) to carry curative genes into human tissues.
• Human gene editing technology: used to disrupt harmful genes or to repair mutated genes.
• Patient-derived cellular gene therapy products: use cells removed from the patient, genetically modified, and then returned to the patient.

Challenges of Gene Therapy

• Delivering the gene to the right place and switching it on.
• Avoiding the immune response.

Breeding

• The application of genetic principles in animal husbandry, agriculture, and horticulture to improve desirable qualities.
• Can occur through selective breeding/artificial selection or natural selection.

Selective Breeding

• The selection of individual animals or plants that show the most desirable characteristics for the next generation in the breeding program.
• Utilizes the natural variations in traits that exist among members of any population.

Plant Breeding

• The science of changing the traits of plants in order to produce desired characteristics.
• Goals include improving grain or biomass yield, end-use quality characteristics (such as taste or the concentrations of specific biological molecules), and ease of processing.
• Plant breeding can be carried out through various techniques, ranging from selecting plants with desirable characteristics for propagation to utilizing methods that make use of knowledge of genetics and chromosomes, to more complex molecular techniques.

Techniques of Plant Breeding

• Mass selection method: A large number of plants of similar phenotype are selected, and their seeds are mixed together to constitute the new variety.
• Pure line selection: A large number of plants are selected from self-pollinated crops, harvested individually, and their individual plant progenies are evaluated; the best progeny is released as a pure line variety.
• Bulk method: F2 and subsequent generations are harvested in mass or as bulk to raise the next generation; finally, individual plants are selected and evaluated.

Types of Selective Breeding/Artificial Selection

• Inbreeding: The process of producing offspring through mating genetically similar organisms; after many generations, the offspring will be almost genetically identical and will produce identical offspring.
• Pure breeds: Animals with a homogeneous appearance, behavior, and other characteristics.
  • Purebred breeding aims to establish and maintain stable traits that the animal can pass on to the next generation, which could help to develop superior qualities.
  • Negative consequence: Makes the expression of undesired recessive traits in the family more likely.
• Crossbreeding: The process of producing offspring through mating two purebred individuals that come from different breeds, varieties, or even species; involves breeding two unrelated individuals; incompatible with the conservation of indigenous breeds.
  • Example: crossbreeding of the local breeds with exotic sires.
• Natural selection: The selection of certain traits without any human intervention.
  • Plants and animals that are better adapted to their environment have a higher chance of survival and producing more offspring than less adapted plants and animals.

Indigenous Knowledge of Ethiopian Farmers

• According to the Central Statistics Agency (CSA, 2020a), Ethiopia has the largest livestock population in Africa, with:
  • 65 million cattle
  • 40 million sheep
  • 51 million goats
  • 8 million camels
  • 49 million chickens in 2020.
• Crop plants such as coffee, safflower, tef, noug, anchote, enset, wheat, barley, sorghum, peas, linseed, castor, finger millet, lentil, and oats are widely produced in Ethiopia.
• Five major cereals (teff, wheat, maize, sorghum, and barley) are the core of Ethiopia’s agriculture and food economy.
• People in Ethiopia have their own indigenous knowledge and practices on how to combat environmental changes, diseases, and plant and animal reproduction, including the selection of desired characteristics, breeding, and management practices on their agricultural activities.
  • For example, selecting the desired quality based on growth rate, body size, resistance to disease and other environmental conditions.

Bioinformatics Introduction

• A modern, growing hybrid field that links biology, computer science, and information technology to support the storage, organization, and retrieval of biological data.
• The design, construction, and use of software tools to generate, store, interpret, and analyze data and information related to biology.
• Provides tools to comprehensively analyze and save large amounts of biological data.
• Useful to improve the diagnosis and detection of diseases.
• Promotes vaccine development by screening databases for pathogen genomes.
• Increases our understanding of evolutionary processes through the analysis of nucleotide/protein sequence mutations.

The field of bioinformatics incorporates three main areas:

1. Genomics: includes DNA sequence data.
2. Proteomics: deals with the function, shapes, interactions, and abundance of proteins.
3. Systems biology:
   • Examines the extensive role of protein and DNA interactions on the function of cells, tissues, and organs, as a whole.
   • The most recent and complex branch in the field of bioinformatics.
   • Can describe the pathway of enzymes and their various metabolites by using computer data models.
   • Can illustrate brain function by using computer images.