Genetics Terminology Notes (Grade 12)

Introduction to Genetics

• Genetics: The foundational scientific discipline dedicated to the study of heredity and the variations observed in inherited characteristics among living organisms.

• Heredity: The biological mechanisms by which genetic information (e.g., eye color, blood type, disease susceptibility) is passed from parent organisms to offspring.

• Variation: The observable differences in these inherited traits among individuals within a family and across broader populations.

Sickle Cell Anaemia as an Example

• Nature: A genetic blood disorder with higher prevalence in populations from malaria-endemic regions (e.g., Africa, Mediterranean, South Asia).

• Cause: A specific point mutation in the gene encoding the beta-globin chain of haemoglobin.

• Effect: Substitution of a single amino acid (valine for glutamic acid) in the haemoglobin molecule.

• Cellular Impact: Under low-oxygen conditions, altered haemoglobin polymerizes, causing red blood cells to deform into rigid, sticky, crescent shapes.

• Physiological Impact: Impairs blood flow, reduces oxygen delivery to tissues, leading to chronic pain, anaemia, organ damage, and increased infection risk.

• Significance: Illustrates how a single gene variation impacts physiology, health, disease pathology, and population-specific disease frequencies.

Chromosomes and Genes

Homologous Pair/Chromosomes:

• Definition: A pair of chromosomes (one maternal, one paternal) that are:

  • Structurally similar (same length, banding patterns).

  • Carry genes for the same set of traits at corresponding loci.

• Example: Human chromosome 1s (one from mother, one from father) form a homologous pair.

• Note: They carry genes for the same traits but may have different alleles (alternative forms of a gene).

Chromosome Structure:

• Long, continuous DNA molecules tightly coiled around specialized proteins (histones).

• Forms chromatin, allowing vast genetic material to fit within the cell nucleus.

Gene:

• Definition: A specific segment of a DNA molecule, serving as the fundamental unit of heredity.

• Function: Carries instructions (nucleotide sequence) for synthesizing a particular protein or functional RNA molecule, dictating a specific trait or biological function.

• Location: Genes are located at precise, fixed positions along a chromosome.

• Example: The gene for lactase persistence (ability to digest lactose into adulthood) is on human chromosome 2, demonstrating the link between a gene and an observable trait.

Locus and Genome

Locus (plural: Loci):

• Definition: The precise, unchanging physical location that a specific gene occupies on a chromosome.

• Importance: Critical for gene mapping and understanding inheritance patterns.

• Example: The gene for oculocutaneous albinism type 1 (OCA1) is at a locus in the 11q14-q21 region of human chromosome 11.

OCA1 - Autosomal Recessive Disorder:

• Requires two copies of the mutated, recessive allele (one from each parent) for expression.

• One mutated allele: Individual is a carrier but typically does not show the phenotype.

Genome:

• Definition: The entire, comprehensive set of genetic material (DNA, or RNA in some viruses) found within an organism.

• Contents: Includes all genes and non-coding regions, spanning all chromosomes of a given species.

• Significance: Central to large-scale biological research, providing a complete genetic blueprint.

Genome Projects and Their Significance

African Genome Program:

• Goal: To sequence the full genetic information of diverse African populations.

• Importance:

  • Capture rich genetic diversity (historically underrepresented).

  • Identify variants contributing to health disparities and specific disease susceptibilities in Africa.

  • Essential for developing culturally and genetically appropriate diagnostics, treatments, and preventative strategies.

  • Promotes equitable genomic healthcare globally.

Human Genome Project (HGP):

• Scope: Monumental international collaborative research (1990-2003).

• Primary Goals:

  • Determine the complete sequence of approximately 3\times10^9 human DNA base pairs.

  • Map and identify all an estimated 2.0\times10^4 to 2.5\times10^4 human genes.

  • Make all sequence data freely and publicly available.

• Key Findings:

  • Fewer genes than initially speculated.

  • Small genetic variation between individuals (around 0.1\%), yet impactful for diversity and disease.

• Impact of HGP (Transformative across domains):

  • In Medicine:

  • Insights into genetic basis of thousands of diseases (Mendelian to complex).

  • Development of diagnostic tools (e.g., genetic tests) and personalized medicine (pharmacogenomics).

  • Advanced therapeutic strategies (gene therapy, CRISPR-based gene editing).

  • In Basic Biology:

  • Deepened understanding of human biology, evolution, and developmental processes.

  • Revealed intricate regulatory networks of genes and extent of non-coding DNA.

  • In Technology:

  • Catalyst for innovations in DNA sequencing (Next-Generation Sequencing).

  • Advances in bioinformatics tools for data management and analysis.

  • Sophisticated computational methods for genomic interpretation.

• Ethical, Legal, and Social Implications (ELSI) (Brought to the forefront):

  • Genetic Privacy: Who owns/accesses genetic information?

  • Discrimination: Potential for discrimination in employment or insurance based on predispositions.

  • Informed Consent: Need for rigorous ethical guidelines in research and clinical applications.

  • Eugenics/Gene Editing Ethics: Debates on responsible application of gene editing (especially germline).

• References:

  • HGP process/significance: https://www.youtube.com/watch?v=- hryHoTIHak&t=43

  • Ethical considerations: https://www.youtube.com/watch?v=A S4wKpK37NY&pp=0gcJCfwAo7VqN5tD&t=677

Gene Occupying Its Locus, Alleles, and Chromosomal Context

Alleles:

• Definition: Different forms or variants of the same gene at a given locus.

• Inheritance: Diploid organisms typically carry two alleles for each gene (one from each parent).

• Example: For eye color, one allele for brown eyes, another for blue eyes at the same locus.

• Meiosis: Ensures each gamete receives only one allele for each gene.

Centromere:

• Definition: Constricted region on a chromosome.

• Role: Organizes chromosome structure, attachment point for spindle fibers during cell division (via kinetochore), ensures accurate segregation of chromosomes to daughter cells.

Allelic Composition at a Locus (Genotype):

• Homozygous:

  • Meaning: Two identical alleles for a particular trait (e.g., FF for dominant, ff for recessive).

  • Also called: Pure breeding.

• Heterozygous:

  • Meaning: Two different alleles for the same characteristic (e.g., Ff - one dominant, one recessive).

  • Also called: Hybrid.

• Significance: This framework explains how genetic information is organized, expressed, and inherited over generations.

Alleles and Their Interactions

• Allele Definition: Alternative form of a gene at the same locus on homologous chromosomes.

• Pea Plant Height Example: T (tall) and t (short) alleles.

Types of Allele Interaction:

• Dominant Allele:

  • Expression: Phenotypic characteristic is expressed whenever at least one copy is present.

  • Effect: Masks the presence of a recessive allele.

  • Example: Brown eye allele (B) is dominant over blue (b); BB or Bb result in brown eyes.

• Recessive Allele:

  • Expression: Trait only expressed when two copies are present (bb - homozygous recessive).

  • Effect: Masked by a dominant allele.

  • Example: Blue eyes appear only with two blue-eye alleles (bb).

• Classic Example of Complete Dominance: Free earlobes are dominant over attached earlobes.

Other Interaction Patterns:

• Incomplete Dominance:

  • Heterozygous phenotype is an intermediate blend of the two homozygous phenotypes.

  • Example: Red snapdragon (RR) x White snapdragon (WW) = Pink snapdragon (RW).

• Codominance:

  • Both alleles are simultaneously and fully expressed in the heterozygous individual, without blending.

  • Example: Human ABO blood group: I^A I^B genotype results in AB blood type (both A and B antigens expressed).

Genetic Expression: Genotype and Phenotype

Genotype:

• Definition: An organism’s specific genetic makeup; the combination of alleles for a trait.

• Representation: Always two letters for a single trait (one allele from each parent).

• Eye Color Examples:

  • BB (homozygous dominant: two brown alleles)

  • Bb (heterozygous: one brown, one blue allele)

  • bb (homozygous recessive: two blue alleles)

• Nature: Internal, inherited genetic code; instructions for building and operating the organism.

Phenotype:

• Definition: The organism’s observable physical appearance, biochemical characteristics, or behavioral traits.

• Determination: Result of the interaction between genotype and environmental factors.

• Eye Color Examples:

  • BB or Bb typically yield a brown-eye phenotype (assuming complete dominance).

  • bb yields a blue-eye phenotype.

• Environmental Influence: Skin color genotype modified by sun exposure.

Additional Concepts:

• Penetrance: Proportion of individuals with a genotype who express the phenotype.

• Expressivity: Degree to which a genotype is expressed in the phenotype.

• Significance: Clarifies how genotype translates to phenotype, and the dynamic role of environment.

Genotype vs Phenotype: A Quick Reference

• Genotype: The internal, inherited genetic information (e.g., BB, Bb, bb).

  • It is the individual's genetic blueprint.

• Phenotype: The external, observable trait expressed by the organism (e.g., brown vs. blue eyes; purple vs. white flowers).

  • It is the outward manifestation.

• Flower Color Example (Purple dominant B, White recessive b):

  • Genotype BB produces a purple phenotype.

  • Genotype Bb produces a purple phenotype (due to dominance).

  • Genotype bb produces a white phenotype.

• Importance: Fundamental for predicting trait expression and analyzing Mendelian inheritance.

Genetic Combinations: Homozygous and Heterozygous

Homozygous:

• Definition: Possessing two identical copies of an allele for a specific characteristic on homologous chromosomes.

• Also known as: Pure breeding.

• Examples: BB (two dominant brown eye alleles) or bb (two recessive blue eye alleles).

• Result: Consistently produce offspring with the same trait when crossed with genetically identical individuals (e.g., BB\times BB).

Heterozygous:

• Definition: Possessing two different alleles for the same characteristic.

• Also known as: Hybrid.

• Example: Bb (one dominant brown eye allele and one recessive blue eye allele).

• Result: Carry both alleles; phenotype expressed depends on dominance relationship.

• Importance: These distinctions are fundamental for predicting inheritance patterns and understanding genetic diversity within a population.

Homozygous vs Heterozygous in Genetics (Visual Summary)

Genetic Diagrams (e.g., Punnett squares):

• Homozygous alleles: Represented by the same letter on both homologous chromosomes (e.g., AA or aa), indicating identical genetic information.

• Heterozygous alleles: Represented by two different letters (e.g., Aa), signifying different alleles from each parent.

Core Distinction:

• Homozygous = same alleles

• Heterozygous = different alleles

• Significance: Critical for predicting phenotypic outcomes in crosses and understanding Mendelian inheritance patterns and genotypic ratios.

Patterns of Inheritance

Monogenic Inheritance:

• Definition: Characteristics controlled primarily by a single gene at a single locus.

• Pattern: Typically follows straightforward Mendelian inheritance, leading to discrete phenotypic categories.

• Example: Albinism (OCA1) — often inherited as a monogenic recessive trait.

  • Requires two copies of the recessive allele for expression.

  • Observed across populations, including in South Africa; traceable via pedigrees.

Polygenic Inheritance:

• Definition: Traits controlled by multiple genes, often interacting, located at multiple loci.

• Pattern: Typically shows a continuous range of variation within a population, rather than discrete categories.

• Example: Human skin color — influenced by at least 10-20 genes and environmental factors (e.g., sun exposure).

  • Results in a wide, continuous spectrum of pigmentation levels across global populations, including in South Africa.

  • Other examples: Height, weight, intelligence, many complex human diseases (diabetes, heart disease).

• Importance: Explains why some traits show simple dominant/recessive ratios, while others display continuous variation, impacting diagnosis, counseling, and public health.

Practice Questions and Answers (Genetics Terminology) – Overview of Answers

Answers to 17 standard practice questions:

• 1) C, 2) B, 3) B, 4) C, 5) D, 6) C, 7) B, 8) C, 9) C, 10) B, 11) C, 12) C, 13) C, 14) C, 15) D, 16) B, 17) C.

• Alignment: Rigorously aligned with key concepts discussed (heredity, inheritance, genotype/phenotype, loci/alleles, homozygous/heterozygous, monogenic/polygenic).

Rationales (typically provided with questions):

• Genetics as the study of heredity and variation.

• Heredity as the transfer mechanism; inheritance as the resulting characteristics.

• Homologous chromosomes and genes as functional units.

• Loci as specific gene positions; alleles as variant forms.

• Dominance relationships; haploid/diploid contexts.

• Monogenic/polygenic patterns; implicit environmental interactions in phenotype.

• Predictive power of concepts for trait outcomes.

Key Terms and Concepts to Remember

• Genetics: Study of heredity and variation.

• Heredity: Transfer of characteristics from parents to offspring.

• Inheritance: Set of characteristics transferred.

• Chromosome: DNA molecule with many genes; humans have 23 pairs.

• Homologous chromosomes: Paired chromosomes with same genes at same loci, one from each parent.

• Gene: DNA sequence with specific function at a locus on a chromosome.

• Locus: Exact position of a gene on a chromosome.

• Genome: Complete set of genes in all chromosomes of an organism.

• Allele: Variant form of a gene at a given locus.

• Dominant allele: Trait expressed if even one copy is present.

• Recessive allele: Trait expressed only when two copies are present.

• Genotype: The two alleles an organism has for a trait (e.g., BB, Bb, bb).

• Phenotype: Observable traits resulting from genotype and environment.

• Homozygous: Two identical alleles for a trait (e.g., BB \text{ or } bb).

• Heterozygous: Two different alleles for a trait (e.g., Bb).

• Monogenic inheritance: Trait controlled by a single gene at one locus.

• Polygenic inheritance: Trait controlled by multiple genes at multiple loci.

• Autosomal recessive: Inheritance where two copies of a mutated allele on an autosome are needed to express the trait (e.g., OCA1).

• Sickle cell anaemia: Disease illustrating heredity and variation with health implications and population frequency differences.

References and Resources

• Video (HGP process/significance): https://www.youtube.com/watch?v=- hryHoTIHak&t=43

• Video (HGP ethical considerations): https://www.youtube.com/watch?v=A S4wKpK37NY&pp=0gcJCfwAo7VqN5tD&t=677

• Ongoing initiatives: African Genome Program (conceptual); Human Genome Project (1990–2003).

Practice Question Answers (Summary from Memo)

• Q1-Q17: C